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New research could be a breakthough in collagen and stem cell research – Truth In Aging

Posted: May 29, 2020 at 9:48 am

New research has identified two actives that can prevent stem cell decline as we age and increase collagen 17 levels in cells. It was published in Nature last year and has just been covered in Scientific American. The study was described as elegant by a prominent dermatologist, not involved in the project. As I am always on the look out for next big thing in antiaging skincare, I pounced.

Ill cut straight to the car chase. The two actives are Y27632 and apocynin and I was curious to see if they could be tracked down outside of a lab and, perhaps, in our potions and lotions. The first is a chemical that I havent been able to track down. Happily, I had better luck with apocynin.

Apocynin has been identified in a specific strain of cannabis, but also in cloudberry. And rubus chamaemorus (AKA cloudberry) seed oil is in a facial oil by Keracell. Ill post a link at the end of this article.

So, how do Y27632 and apocynin work? Emi Nishimura, a professor of stem cell biology at Tokyo Medical and Dental University in Japan, revealed that aging and UV exposure deplete stem cells of a crucial collagen protein. Heres what happens.

As part of normal skin health, the top layer of the epidermis is constantly being sloughed off and replaced from a self-replenishing pool of stem cells in the basal layer. These stem cells have roots that anchor them to a thin piece of tissue called the basement membrane that connects the epidermis and the dermis. Only when tethered can they replicate and mature into another type of cell.

This is where collagen 17 comes in. This collagen protein does the tethering (see the "adhesive molecule" in the illustration above), rooting the stem cell to the basement membrane. As stem cells become damaged, they lose precious amounts of collagen 17. The more protein they lose, the weaker their bond to the basement membrane, until eventually they are forced out by neighboring healthy cells.

Thats why this study is potentially a breakthrough. It has identified the process, the key protein that needs to be replenished and the chemicals that might just be able to do that.

You can find rubus chamaemorus (AKA cloudberry) seed oil and a potential source of apocynin in KERACELL Liquid Gold Enriching Elixir ($160 in the shop).

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New research could be a breakthough in collagen and stem cell research - Truth In Aging

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Shanghai Cell Therapy Group Launches Collaboration with USC researcher to Improve the ex vivo Expansion of Hematopoietic Stem Cells for Clinical…

Posted: May 28, 2020 at 3:46 am

SHANGHAI, May27, 2020 /PRNewswire/ -- Shanghai Cell Therapy Group (SHCell) recently entered intoa six-year research collaborative project with Professor Qi-Long Ying from the University of Southern California (USC). Through the project, sponsored by $3.6 million from the Baize Plan Fund, the Ying laboratory aims to develop conditions for the long-term ex vivo expansion of mouse and human hematopoietic stem and progenitor cells.

"Hematopoietic stem cells, or HSCs, are found in the bone marrow of adults," said Professor Qijun Qian, CEO of Shanghai Cell Therapy Group. "HSCs have the ability for long-term self-renewal and differentiation into various types of mature blood cells, and for rebuilding normal hematopoiesis and immune function in patients. They also have enormous potential to treat diseases, including tumors, autoimmune diseases, severe infectious disease, and inherited blood diseases, and to combat the effects of aging."

This research project will be conducted and supervised by Professor Qi-Long Ying, a Professor of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC. Professor Ying's pioneering stem cell research has won international acclaim, including the 2016 McEwen Award for Innovation, the highest honor in the field.

"We'll develop and optimize culture conditions for the long-term ex vivo expansion of HSCs," said Professor Ying. "We'll also test combinations of basal media, small molecules, cytokines and growth factors, and characterize ex vivo expanded hematopoietic stem and progenitor cells. These cells will then be genetically modified and tested for their potential to treat different diseases, including blood disorders and cancers."

Professor Andrew P. McMahon, Director of Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research of USC, added: "Stem cell biology represents an exciting area in medicine with great therapeutic potential. I am delighted SHCell is supporting Professor Ying. A breakthrough in the ability to propagate and manipulate HSCs will have lasting clinical significance."

The project also plans to build animal models of different blood diseases and cancers and test the safety and effectiveness of genetically modified hematopoietic stem and progenitor cells before clinical translation. SHCell will actively explore clinical applications of hematopoietic stem and progenitor cells in the treatment of cancers or blood diseases.

As SHCell's first overseas collaboration, this project aims to advance the goals of the Baize Plan: to provide first-class cell treatments and cell therapies at an affordable price to cure cancer and increase life expectancy. SHCell hopes that this project will also accelerate original scientific breakthroughs in the stem cell field.

Shanghai Cell Therapy Group

Founded in 2013, Shanghai Cell Therapeutics Group Co., Ltd is located at the Shanghai Municipal Engineering and Technology Research Center, which was established by the Shanghai Science and Technology Commission. With a mission of "changing the length and abundance of life with cell therapy", SHCell has created a closed-loop industrial chain and an integrated platform for cell treatment and cell therapy. It comprises cell storage, cell drug research and cell clinical transformation with cell therapy as its core business.

The Baize Plan was proposed in 2016 by Wu Mengchao, an Academician of the Chinese Academy of Sciences (CAS) and initiated by Professor Qian, aiming to provide first-class cell treatments and cell therapies at an affordable price with the goal of curing cancers and increasing life expectancy. The Baize Plan Fund was created by the Shanghai Cell Therapy Group to realize the vision of the Baize Plan.

University of Southern California (USC)

Founded in 1880, the University of Southern California is one of the world's leading educational and research institutions, and also the oldest private research university in California. Located in the heart of Los Angeles, the University of Southern California comprises 23 schools and units, and students are encouraged to explore different fields of study. The University of Southern California ranked #22 in National Universities in the 2020 edition of Best Colleges, published by U.S. News & World Report.

For more information, visit http://www.shcell.com/

SOURCE Shanghai Cell Therapy Group

http://www.shcell.com

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Shanghai Cell Therapy Group Launches Collaboration with USC researcher to Improve the ex vivo Expansion of Hematopoietic Stem Cells for Clinical...

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On the Origins of Modern Biology and the Fantastic: Part 19 Nalo Hopkinson and Stem Cell Research – tor.com

Posted: May 28, 2020 at 3:46 am

She just wanted to be somewhere safe, somewhere familiar, where people looked and spoke like her and she could stand to eat the food. Midnight Robber by Nalo Hopkinson

Midnight Robber (2000) is about a woman, divided. Raised on the high-tech utopian planet of Touissant, Tan-Tan grows up on a planet populated by the descendants of a Caribbean diaspora, where all labor is performed by an all-seeing AI. But when she is exiled to Touissants parallel universe twin planet, the no-tech New Half-Way Tree, with her sexually abusive father, she becomes divided between good and evil Tan-Tans. To make herself and New Half-Way Tree whole, she adopts the persona of the legendary Robber Queen and becomes a legend herself. It is a wondrous blend of science fictional tropes and Caribbean mythology written in a Caribbean vernacular which vividly recalls the history of slavery and imperialism that shaped Touissant and its people, published at a time when diverse voices and perspectives within science fiction were blossoming.

Science fiction has long been dominated by white, Western perspectives. Vernes tech-forward adventures and Wells sociological allegories established two distinctive styles, but still centered on white imperialism and class struggle. Subsequent futures depicted in Verne-like pulp and Golden Age stories, where lone white heroes conquered evil powers or alien planets, mirrored colonialist history and the subjugation of non-white races. The civil rights era saw the incorporation of more Wellsian sociological concerns, and an increase in the number of non-white faces in the future, but they were often tokensparts of a dominant white monoculture. Important figures that presaged modern diversity included Star Treks Lieutenant Uhura, played by Nichelle Nichols. Nichols was the first black woman to play a non-servant character on TV; though her glorified secretary role frustrated Nichols, her presence was a political act, showing there was space for black people in the future.

Another key figure was the musician and poet Sun Ra, who laid the aesthetic foundation for what would become known as the Afrofuturist movement (the term coined by Mark Dery in a 1994 essay), which showed pride in black history and imagined the future through a black cultural lens. Within science fiction, the foundational work of Samuel Delany and Octavia Butler painted realistic futures in which the histories and cultural differences of people of color had a place. Finally, an important modern figure in the decentralization of the dominant Western perspective is Nalo Hopkinson.

A similarly long-standing paradigm lies at the heart of biology, extending back to Darwins theoretical and Mendels practical frameworks for the evolution of genetic traits via natural selection. Our natures werent determined by experience, as Lamarck posited, but by genes. Therefore, genes determine our reproductive fitness, and if we can understand genes, we might take our futures into our own hands to better treat disease and ease human suffering. This theory was tragically over-applied, even by Darwin, who in Descent of Man (1871) conflated culture with biology, assuming the Wests conquest of indigenous cultures meant white people were genetically superior. After the Nazis committed genocide in the name of an all-white future, ideas and practices based in eugenics declined, as biological understanding of genes matured. The Central Dogma of the 60s maintained the idea of a mechanistic meaning of life, as advances in genetic engineering and the age of genomics enabled our greatest understanding yet of how genes and disease work. The last major barrier between us and our transhumanist future therefore involved understanding how genes determine cellular identity, and as well see, key figures in answering that question are stem cells.

***

Hopkinson was born December 20, 1960 in Kingston, Jamaica. Her mother was a library technician and her father wrote, taught, and acted. Growing up, Hopkinson was immersed in the Caribbean literary scene, fed on a steady diet of theater, dance, readings, and visual arts exhibitions. She loved to readfrom folklore, to classical literature, to Kurt Vonnegutand loved science fiction, from Spock and Uhura on Star Trek, to Le Guin, James Tiptree Jr., and Delany. Despite being surrounded by a vibrant writing community, it didnt occur to her to become a writer herself. What they were writing was poetry and mimetic fiction, Hopkinson said, whereas I was reading science fiction and fantasy. It wasnt until I was 16 and stumbled upon an anthology of stories written at the Clarion Science Fiction Workshop that I realized there were places where you could be taught how to write fiction. Growing up, her family moved often, from Jamaica to Guyana to Trinidad and back, but in 1977, they moved to Toronto to get treatment for her fathers chronic kidney disease, and Hopkinson suddenly became a minority, thousands of miles from home.

Development can be described as an orderly alienation. In mammals, zygotes divide and subsets of cells become functionally specialized into, say, neurons or liver cells. Following the discovery of DNA as the genetic material in the 1950s, a question arose: did dividing cells retain all genes from the zygote, or were genes lost as it specialized? British embryologist John Gurdon addressed this question in a series of experiments in the 60s using frogs. Gurdon transplanted nuclei from varyingly differentiated cells into oocytes stripped of their genetic material to see if a new frog was made. He found the more differentiated a cell was, the lower the chance of success, but the successes confirmed that no genetic material was lost. Meanwhile, Canadian biologists Ernest McCulloch and James Till were transplanting bone marrow to treat irradiated mice when they noticed it caused lumps in the mices spleens, and the number of lumps correlated with the cellular dosage. Their lab subsequently demonstrated that each lump was a clonal colony from a single donor cell, and a subset of those cells was self-renewing and could form further colonies of any blood cell type. They had discovered hematopoietic stem cells. In 1981 the first embryonic stem cells (ESCs) from mice were successfully propagated in culture by British biologist Martin Evans, winning him the Nobel Prize in 2007. This breakthrough allowed biologists to alter genes in ESCs, then use Gurdons technique to create transgenic mice with that alteration in every cellcreating the first animal models of disease.

In 1982, one year after Evans discovery, Hopkinson graduated with honors from York University. She worked in the arts, as a library clerk, government culture research officer, and grants officer for the Toronto Arts Council, but wouldnt begin publishing her own fiction until she was 34. [I had been] politicized by feminist and Caribbean literature into valuing writing that spoke of particular cultural experiences of living under colonialism/patriarchy, and also of writing in ones own vernacular speech, Hopkinson said. In other words, I had models for strong fiction, and I knew intimately the body of work to which I would be responding. Then I discovered that Delany was a black man, which opened up a space for me in SF/F that I hadnt known I needed. She sought out more science fiction by black authors and found Butler, Charles Saunders, and Steven Barnes. Then the famous feminist science fiction author and editor Judy Merril offered an evening course in writing science fiction through a Toronto college, Hopkinson said. The course never ran, but it prompted me to write my first adult attempt at a science fiction story. Judy met once with the handful of us she would have accepted into the course and showed us how to run our own writing workshop without her. Hopkinsons dream of attending Clarion came true in 1995, with Delany as an instructor. Her early short stories channeled her love of myth and folklore, and her first book, written in Caribbean dialect, married Caribbean myth to the science fictional trappings of black market organ harvesting. Brown Girl in the Ring (1998) follows a young single mother as shes torn between her ancestral culture and modern life in a post-economic collapse Toronto. It won the Aspect and Locus Awards for Best First Novel, and Hopkinson was awarded the John W. Campbell Award for Best New Writer.

In 1996, Dolly the Sheep was created using Gurdons technique to determine if mammalian cells also could revert to more a more primitive, pluripotent state. Widespread animal cloning attempts soon followed, (something Hopkinson used as a science fictional element in Brown Girl) but it was inefficient, and often produced abnormal animals. Ideas of human cloning captured the public imagination as stem cell research exploded onto the scene. One ready source for human ESC (hESC) materials was from embryos which would otherwise be destroyed following in vitro fertilization (IVF) but the U.S. passed the Dickey-Wicker Amendment prohibited federal funding of research that destroyed such embryos. Nevertheless, in 1998 Wisconsin researcher James Thomson, using private funding, successfully isolated and cultured hESCs. Soon after, researchers around the world figured out how to nudge cells down different lineages, with ideas that transplant rejection and genetic disease would soon become things of the past, sliding neatly into the hole that the failure of genetic engineering techniques had left behind. But another blow to the stem cell research community came in 2001, when President Bushs stem cell ban limited research in the U.S. to nineteen existing cell lines.

In the late 1990s, another piece of technology capturing the public imagination was the internet, which promised to bring the world together in unprecedented ways. One such way was through private listservs, the kind used by writer and academic Alondra Nelson to create a space for students and artists to explore Afrofuturist ideas about technology, space, freedom, culture and art with science fiction at the center. It was wonderful, Hopkinson said. It gave me a place to talk and debate with like-minded people about the conjunction of blackness and science fiction without being shouted down by white men or having to teach Racism 101. Connections create communities, which in turn create movements, and in 1999, Delanys essay, Racism and Science Fiction, prompted a call for more meaningful discussions around race in the SF community. In response, Hopkinson became a co-founder of the Carl Brandon society, which works to increase awareness and representation of people of color in the community.

Hopkinsons second novel, Robber, was a breakthrough success and was nominated for Hugo, Nebula, and Tiptree Awards. She would also release Skin Folk (2001), a collection of stories in which mythical figures of West African and Afro-Caribbean culture walk among us, which would win the World Fantasy Award and was selected as one ofThe New York Times Best Books of the Year. Hopkinson also obtained masters degree in fiction writing (which helped alleviate U.S. border hassles when traveling for speaking engagements) during which she wrote The Salt Roads (2003). I knew it would take a level of research, focus and concentration I was struggling to maintain, Hopkinson said. I figured it would help to have a mentor to coach me through it. That turned out to be James Morrow, and he did so admirably. Roads is a masterful work of slipstream literary fantasy that follows the lives of women scattered through time, bound together by the salt uniting all black life. It was nominated for a Nebula and won the Gaylactic Spectrum Award. Hopkinson also edited anthologies centering around different cultures and perspectives, including Whispers from the Cotton Tree Root: Caribbean Fabulist Fiction (2000), Mojo: Conjure Stories (2003), and So Long, Been Dreaming: Postcolonial Science Fiction & Fantasy (2004). She also came out with the award-winning novelThe New Moons Arms in 2007, in which a peri-menopausal woman in a fictional Caribbean town is confronted by her past and the changes she must make to keep her family in her life.

While the stem cell ban hamstrung hESC work, Gurdons research facilitated yet another scientific breakthrough. Researchers began untangling how gene expression changed as stem cells differentiated, and in 2006, Shinya Yamanaka of Kyoto University reported the successful creation of mouse stem cells from differentiated cells. Using a list of 24 pluripotency-associated genes, Yamanaka systematically tested different gene combinations on terminally differentiated cells. He found four genesthereafter known as Yamanaka factorsthat could turn them into induced-pluripotent stem cells (iPSCs), and he and Gurdon would share a 2012 Nobel prize. In 2009, President Obama lifted restrictions on hESC research, and the first clinical trial involving products made using stem cells happened that year. The first human trials using hESCs to treat spinal injuries happened in 2014, and the first iPSC clinical trials for blindness began this past December.

Hopkinson, too, encountered complications and delays at points in her career. For years, Hopkinson suffered escalating symptoms from fibromyalgia, a chronic disease that runs in her family, which interfered with her writing, causing Hopkinson and her partner to struggle with poverty and homelessness. But in 2011, Hopkinson applied to become a professor of Creative Writing at the University of California, Riverside. It seemed in many ways tailor-made for me, Hopkinson said. They specifically wanted a science fiction writer (unheard of in North American Creative Writing departments); they wanted someone with expertise working with a diverse range of people; they were willing to hire someone without a PhD, if their publications were sufficient; they were offering the security of tenure. She got the job, and thanks to a steady paycheck and the benefits of the mild California climate, she got back to writing. Her YA novel, The Chaos (2012), coming-of-age novelSister Mine (2013), and another short story collection, Falling in Love with Hominids (2015) soon followed. Her recent work includes House of Whispers (2018-present), a series in DC Comics Sandman Universe, the final collected volume of which is due out this June. Hopkinson also received an honorary doctorate in 2016 from Anglia Ruskin University in the U.K., and was Guest of Honor at 2017 Worldcon, a year in which women and people of color dominated the historically white, male ballot.

While the Yamanaka factors meant that iPSCs became a standard lab technique, iPSCs are not identical to hESCs. Fascinatingly, two of these factors act together to maintain the silencing of large swaths of DNA. Back in the 1980s, researchers discovered that some regions of DNA are modified by small methyl groups, which can be passed down through cell division. Different cell types have different DNA methylation patterns, and their distribution is far from random; they accumulate in the promoter regions just upstream of genes where their on/off switches are, and the greater the number of methyl groups, the lesser the genes expression. Furthermore, epigenetic modifications, like methylation, can be laid down by our environments (via diet, or stress) which can also be passed down through generations. Even some diseases, like fibromyalgia, have recently been implicated as such an epigenetic disease. Turns out that the long-standing biological paradigm that rejected Lamarck also missed the bigger picture: Nature is, in fact, intimately informed by nurture and environment.

In the past 150 years, we have seen ideas of community grow and expand as the world became more connected, so that they now encompass the globe. The histories of science fiction and biology are full of stories of pioneers opening new doorsbe they doors of greater representation or greater understanding, or bothand others following. If evolution has taught us anything, its that nature abhors a monoculture, and the universe tends towards diversification; healthy communities are ones which understand that we are not apart from the world, but of it, and that diversity of types, be they cells or perspectives, is a strength.

Kelly Lagor is a scientist by day and a science fiction writer by night. Her work has appeared at Tor.com and other places, and you can find her tweeting about all kinds of nonsense @klagor

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On the Origins of Modern Biology and the Fantastic: Part 19 Nalo Hopkinson and Stem Cell Research - tor.com

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Leonhardts Launchpads Announces Issuance of New U.S. Patent for Bioelectric Plus Biologics Platform for Organ Regeneration and Healing – Life Pulse…

Posted: May 28, 2020 at 3:46 am

United States, California, Irvine 05-27-2020 (PRDistribution.com) Latest Patent Further Strengthens Intellectual Property Portfolio Covering Novel Platform for Precisely ControllingRegenerative Protein Expressions Including Stem Cell Homing and Differentiation Control

Technology Has Key Potential Applications in Regeneration of Failing Heart, Brain, Kidney, Liver, Pancreas, Lungs, Aorta, Vision and Hearing as well as Transcutaneous Uses for Accelerated Wound Healing, Skin, Hair and Penile Function Regeneration (ED)Irvine, California, May 27th, 2020 Leonhardts Launchpads, an innovation and startup launch accelerator focused on developing novel therapeutics that harness the bodys innate mechanisms to regenerate failing organs and to heal tissues, today announced the issuance of a new U.S. patent providing broad protection for the companys first-of-its-kind combination bioelectrics and biologics technology platform, which has multiple potential therapeutic applications in organ regeneration and recovery. Previous stem cell therapies that delivered stem cells alone in a single application failed to regenerate organs fully. Electrical stimulation technologies to date have failed to zero in on and deliver the precise right bioelectric signaling sequences for controlling specific regenerative protein expressions when and where needed. This pioneering technology platform is the first to combine the powerful ability of bioelectric stimulation with repeat deliveries of not just stem cells but a whole host of support factors similar to an egg yolk designed to help cells survive, proliferate, engraft and differentiate with the intention of fully regenerating failing organs. stated primary inventor, Executive Chairman and CEO Howard J. Leonhardt. U.S. Patent 10,646,644 Issued May 12th, 2020 https://patents.justia.com/patent/10646644covers bioelectric stimulation controlled release of SDF1 and PDGF known stem cell homing and proliferation factors as well as use of a re-fillable micro infusion pump for slow infusion of a mixed composition of stem cells, exosomes, micro RNAs, nutrient hydrogel, growth factor cocktail, selected alkaloids and anti-inflammatory agents with the intention of regenerating organs and healing tissues. SDF1 and PDGF highlighted in these new patent claims also have strong capabilities in promoting arteriogenesis (mature blood vessel growth).The Leonhardt team has separately filed or acquired patent claims for bioelectric controlled expression of follistatin, klotho, tropoelastin, VEGF, IGF1, CXCL5, HIF1a, EGF, HGF, OPG, RANKL and COL17A1 all known to have a role in organ healing https://patents.justia.com/patent/20180064935. Separately the Leonhardts Launchpads startup CancerCell has 9 issued U.S. patents https://cancercellinc.com/list-of-the-issued-cancer-patents/ for bioelectric treatment of cancer and dozens of additional cancer treatment related claims pending https://patents.justia.com/patent/20190030330. The team has filed patent clams on the combination of bioelectric stimulation and PRF https://patents.justia.com/patent/20200000709. Other important patent filings have been submitted on bioelectric inflammation management https://patents.justia.com/patent/20190022389 and blood pressure management https://patents.justia.com/patent/20190022396The Leonhardts Launchpads technology platform is based on foundational scientific research that began in the late 1980s working with Dr. Race Kao and Dr. George Magovern Sr. in Pittsburgh when they injected satellite cells (myoblasts or muscle stem cells) to repair damaged heart tissue in dogs and published the results in The Physiologist in 1989. In 1995 Howard Leonhardt filed his first patent for a stem cell and biologics delivery system for organ repair ProCell https://patents.google.com/patent/US5693029A/en based on work that began in 1988. In 1998 the Leonhardt team began collaboration with Dr. Doris Taylor whom that year published a landmark paper in Nature Medicine https://www.nature.com/articles/nm0898-929 on repair of infarcted hearts with myoblast cells. Dr. Taylor currently still serves as co-chair of our Scientific Advisory Board today. In 1999 the Leonhardt team worked with Dr. Shinichi Kanno to publish in Circulation, the Journal of the American Heart Association, pioneering results with bioelectric stimulation driven VEGF protein expression for limb salvage via angiogenesis in animals https://www.ahajournals.org/doi/abs/10.1161/01.cir.99.20.2682 and filed a patent application for the same within a year. Since then the Leonhardt team and LeonhardtsLaunchpads and itsportfolio of startupshas had issued, pending,optioned orlicensed over 600patentclaims for organregeneration andrecovery. In 2001 Howard Leonhardt and Dr. Juan Chachques filed patents on bioelectric stimulation controlled myogenesis and dynamic cardiac support with an early less potent stem cell homing signal. That same year a Leonhardt led team working with Dr. Patrick Serruys completed the landmark first ever case of non-surgical cell based regeneration of a damaged human heart in The Netherlands. Howard Leonhardt began a collaboration at that time with Dr. Jorge Genovese co-inventor of this patent, and BioLeonhardts VP of Bioelectric Regeneration Research, that continues to this day. Over 200 dedicated talented people help Leonhardts Launchpads and its startups advance their developments almost every day see Team https://leonhardtventures.com/team/ and Scientific Advisory Board https://calxstars.com/scientific-advisory-board/.About Leonhardts Launchpads:Leonhardts Launchpads by Cal-X Stars Business Accelerator, Inc. in California, Leonhardts Launchpads Utah, Inc., Leonhardts Launchpads Australia PTY and Leonhardts Launchpads branches in Minneapolis, Pittsburgh and Brazil are the innovation and startup launch accelerator arms of Leonhardt Ventures (Leonhardt Vineyards LLC DBA Leonhardt Ventures). Leonhardt Ventures has been developing breakthrough medtech and biotech innovations since the 1980s. In the 1980s the team patented, developed and commercialized the PolyCath line of cardiovascular balloon catheters. In the 1990s they developed and completed the first non-surgical repair of an aortic aneurysm (Melbourne, Australia 1995) and patented what is still today the leading endovascular stent graft for aortic aneurysm repair. In that time period they also patented one of the first percutaneous heart valve systems. Since 2000 the team has been focused almost exclusively on stem cell, biologics and bioelectric based organ regeneration and healing. In May of 2001 the team completed the landmark first ever non-surgical case of cell therapy for heart damage recovery. In 2008 the team began exploring if what they had learned from research in regenerating hearts could be translated to other organs. The organization now has 30 related startups and organ specific innovations in its 2020 portfolio class https://leonhardtventures.com/development-pipeline/ in these groups (1) Heart & Cardiovascular, (2) Brain, (3) Cosmetic & Reproductive Health, (4) Major Organ Regeneration and (5) Cancer. The accelerator business model is to accelerate each organ specific innovation through first in human studies and then secure a strategic partner to advance the product through commercialization. Click on Leonhardt Ventures and Leonhardts Launchpads 2020 Annual Report for more information https://leonhardtventures.com/wp-content/uploads/2020/04/4_23_2020.pdfand our web site at http://www.leonhardtventures.comSee previous PDGF related press release https://www.biospace.com/article/releases/-b-leonhardt-b-and-b-genovese-b-file-patent-for-bioelectric-controlled-expression-of-pdgf-a-powerful-organ-regeneration-cytokine-/See previous KLOTHO anti-aging related press release https://www.biospace.com/article/leonhardt-s-launchpads-announces-filing-of-patent-for-bioelectric-stimulation-controlled-klotho-expression-powerful-anti-aging-and-regeneration-promoting-protein-/Contact See contact page on web site for contact information for all locations and phone numbers https://leonhardtventures.com/contact/Leonhardts Launchpads[emailprotected]Warning and Disclaimers: Product(s) are not yet proven safe or effective. Patents pending may not be issued. Patents licensed or optioned may not be maintained. Patents issued may be invalidated. Products are in early stage development. Forward looking statements may change without notice. As an investment these startups mentioned are in the highest risk category for total loss and only suitable for sophisticated experienced accredited investors. The company does not have on hand sufficient resources to bring these products through clinical studies and may not obtain these resources. The company is under staffed and under funded compared to most other participants in this space. Due to a small staff at the accelerator to maintain all web sites and other published materials they may not be fully up to date and there may be out date inaccurate information. If you have any questions on our products or our company please write us to ask.Leonhardts Launchpads by Cal-X Stars,18575 Jamboree Rd #6, Irvine, CA 92612Leonhardts Launchpads Utah, Inc.Research Lab @ 2500 S State St. #D249, Salt Lake City, UT 84115

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Company Name: Leonhardts Launchpads by Cal-X Stars Business Accelerator, Inc.Full Name: Howard J. LeonhardtPhone: (424) 291-2133Email Address: Send EmailWebsite: http://www.leonhardtventures.com

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Leonhardts Launchpads Announces Issuance of New U.S. Patent for Bioelectric Plus Biologics Platform for Organ Regeneration and Healing - Life Pulse...

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Research at MDI Biological Laboratory explores novel pathways of regeneration and tumorigenesis – Bangor Daily News

Posted: May 28, 2020 at 3:46 am

BAR HARBOR Research by scientists at the MDI Biological Laboratoryis opening up new approaches to promoting tissue regeneration in organs damaged by disease or injury.

In recent years, research in regenerative biology has focused on stem cell therapies that reprogram the bodys own cells to replace damaged tissue, which is a complicated process because it involves turning genes in the cells nucleus on and off.

A recent paper in the journal Genetics by MDI Biological Laboratory scientist Elisabeth Marnik, Ph.D., a postdoctoral fellow in the laboratory of Dustin Updike, Ph.D., offers insight into an alternate pathway to regeneration: by recreating the properties of germ cells.

Germ cells, which are the precursors to the sperm and egg, are considered immortal because they are the only cells in the body with the potential to create an entirely new organism. The stem cell-like ability of germ cells to turn into any type of cell is called totipotency.

By getting a handle on what makes germ cells totipotent, we can promote regeneration by unlocking the stem cell-like properties of other cell types, said Updike. Our research shows that such cells can be reprogrammed by manipulating their cytoplasmic composition and chemistry, which would seem to be safer and easier than changing the DNA within a cells nucleus.

Using the tiny, soil-dwelling nematode worm, C. elegans, as a model, the Updike lab studies organelles called germ granules that reside in the cytoplasm (the contents of the cell outside of the nucleus) of germ cells. These organelles, which are conserved from nematodes to humans, are one of the keys to the remarkable attributes of germ cells, including the ability to differentiate into other types of cells.

In their recent paper entitled Germline Maintenance Through the Multifaceted Activities of GLH/Vasa in Caenorhabditis elegans P Granules, Updike and his team describe the intriguing and elusive role of Vasa proteins within germ granules in determining whether a cell is destined to become a germ cell with totipotent capabilities or a specific type of cell, like those that comprise muscle, nerves or skin.

Because of the role of Vasa proteins in preserving totipotency, an increased understanding of how such proteins work could lead to unprecedented approaches to de-differentiating cell types to promote regeneration; or alternatively, to new methods to turn off totipotency when it is no longer desirable, as in the case of cancer.

The increase in chronic and degenerative diseases caused by the aging of the population is driving demand for new therapies, said MDI Biological Laboratory President Hermann Haller, M.D. Dustins research on germ granules offers another route to repairing damaged tissues and organs in cases where therapeutic options are limited or non-existent, as well as an increased understanding of cancer.

Because of the complexity of the cellular chemistry, research on Vasa and other proteins found in germ granules is often overlooked, but that is rapidly changing especially among pharmaceutical companies as more scientists realize the impact and potential of such research, not only for regenerative medicine but also for an understanding of tumorigenesis, or cancer development, Updike said.

Recent research has found that some cancers are accompanied by the mis-expression of germ granule proteins, which are normally found only in germ cells. The mis-expression of these germ-granule proteins seems to promote the immortal properties of germ cells, and consequently tumorigenesis, with some germ-granule proteins now serving as prognosis markers for different types of cancer, Updike said.

Updike is a former postdoctoral researcher in the laboratory of Susan Strome, Ph.D., at University of California, Santa Cruz. Strome, who was inducted into the National Academy of Sciences last year, first discovered P granules more than 30 years ago. She credits Updike, who has published several seminal papers on the subject, with great imagination, determination and excellent technical skill in the pursuit of his goal of elucidating the function and biochemistry of these tiny organelles.

The lead author of the new study from the Updike laboratory, Elisabeth A. Marnik, Ph.D., will be launching her own laboratory at Husson University in Bangor, Maine, this fall. Other contributors include J. Heath Fuqua, Catherine S. Sharp, Jesse D. Rochester, Emily L. Xu and Sarah E. Holbrook. Their research was conducted at the Kathryn W. Davis Center for Regenerative Biology and Medicine at the MDI Biological Laboratory.

Updikes research is supported by a grant (R01 GM-113933) from the National Institute of General Medical Sciences (NIGMS), an institute of the National Institutes of Health (NIH). The equipment and cores used for part of the study were supported by NIGMS-NIH Centers of Biomedical Research Excellence and IDeA Networks of Biomedical Research Excellence grants P20 GM-104318 and P20 GM-203423, respectively.

We aim to improve human health and healthspan by uncovering basic mechanisms of tissue repair, aging and regeneration, translating our discoveries for the benefit of society and developing the next generation of scientific leaders. For more information, please visitmdibl.org.

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ViaCyte Announces $27 Million Financing to Advance Next Generation Cell Therapies for Diabetes – Yahoo Finance

Posted: May 28, 2020 at 3:46 am

PEC-Direct: Clinical data from ViaCyte's product candidate has shown that implanted cells, when effectively engrafted, are capable of producing circulating C-peptide, a biomarker for insulin, in patients with type 1 diabetes

PEC-Encap: ViaCyte's cell therapy product candidate designed to treat all patients with insulin requiring diabetes is being studied in the clinic utilizing an encapsulated delivery technology developed in collaboration with W.L. Gore & Associates

PEC-QT: ViaCyte, in collaboration with CRISPR Therapeutics, is developing a product candidate for diabetes; based on an immune-evasive stem cell line, this approach has the potential to further broaden the availability of cell therapy for other diseases

The Company also announced board chair succession, naming Ian F. Smith as Executive Chairperson

SAN DIEGO, May 26, 2020 /PRNewswire/ --ViaCyte, Inc., a privately held regenerative medicine company, today announced the close of an approximately $27 million private financing, part of the Series D preferred stock financing entered into in late 2018. Investors included, Bain Capital Life Sciences, TPG Capital, RA Capital Management, Sanderling Ventures, and several individual supporters of the Company. Proceeds from the financing will be used to further advance the Company's multi-product candidate approach to develop medicines that have the potential to transform the way insulin-requiring diabetes is managed, potentially providing a functional cure for patients with type 1 diabetes.

ViaCyte logo. (PRNewsFoto/ViaCyte, Inc.)

Coinciding with the financing, the Company also appointed Ian F. Smithas Executive Chairperson. Mr. Smith was appointed to the Company's Board of Directors in July 2019 and succeeds Fred Middleton, who remains on the board.

Commenting on the financing, Paul Laikind, Ph.D., Chief Executive Officer and President of ViaCyte, said, "During these difficult times we are grateful for the continued support of our investors as well as our clinical trial participants, whose safety and health remains our focus and commitment. We are steadfast in our mission to deliver potentially life sustaining therapies for patients with insulin-requiring diabetes and to continue the significant progress we have made in the past year. ViaCyte is the first company to demonstrate production of C-peptide, a biomarker for insulin, in patients with type 1 diabetes receiving a stem cell-derived islet replacement. Moving forward, we are optimizing the effectiveness of both PEC-Direct and PEC-Encap, the latter of which incorporates novel device material technology created in collaboration with W.L. Gore & Associates. We are also making important progress on our PEC-QT program with our partner, CRISPR Therapeutics, and are now moving into pre-IND activities. This program is designed to eliminate the need for immuno-suppression and could have a transformative impact on a broader population of insulin-dependent patients."

Dr. Laikind continued, "In conjunction with the closure of the financing, we are also pleased to announce the appointment of Ian F. Smith as our Executive Chairperson, succeeding Fred Middleton. Since joining the board last July, Ian and I have worked closely to accelerate ViaCyte's growth and prepare for the future. We are extremely grateful to Fred for his many years of service as Chairperson of ViaCyte's Board of Directors. Throughout his time leading the Board, Fred provided expert guidance as ViaCyte has consistently broken new ground in the field of regenerative medicine and cell replacement therapies."

Story continues

Mr. Middleton said, "I am proud to have chaired the Board as ViaCyte developed into a leading company in the regenerative medicine field.I am confident that Ian's unique expertise and executive leadership, specifically with innovative growth-oriented companies, and specifically in corporate strategy and operations, as well as capital markets will help ViaCyte progress its important work and firmly establish itself as a leader in the cell therapy sector."

About ViaCyte's Pipeline

The PEC-Direct product candidate, currently being evaluated in the clinic, delivers ViaCyte's PEC-01 cells (pancreatic islet progenitor cells) in a non-immunoprotective device and is being developed for type 1 diabetes patients who have hypoglycemia unawareness, extreme glycemic lability, and/or recurrent severe hypoglycemic episodes. The PEC-Encap (also known as VC-01) product candidate, also undergoing clinical evaluation, delivers the same pancreatic islet progenitor cells but in an immunoprotective device. PEC-Encap is being developed for all patients with type 1 diabetes. In collaboration with CRISPR Therapeutics, ViaCyte is developing immune-evasive stem cell lines from its proprietary CyT49 cell line. These immune-evasive stem cell lines, which are being used in the PEC-QT program, have the potential to further broaden the availability of cell therapy for all patients with insulin-requiring diabetes, type 1 and type 2. In addition, a pluripotent, immune evasive cell line has the potential to be used to produce any cell in the body, thus enabling many other potential indications.

About ViaCyte

ViaCyte is a privately held regenerative medicine company developing novel cell replacement therapies as potential long-term diabetes treatments to achieve glucose control targets and reduce the risk of hypoglycemia and diabetes-related complications. ViaCyte's product candidates are based on directed differentiation of pluripotent stem cells into PEC-01 pancreatic islet progenitor cells, which are then implanted in durable and retrievable cell delivery devices. Over a decade ago, ViaCyte scientists were the first to report on the production of pancreatic cells from a stem cell starting point and the first to demonstrate in an animal model of diabetes that, once implanted and matured, these cells secrete insulin and other pancreatic hormones in response to blood glucose levels and can be curative. More recently, ViaCyte demonstrated that when effectively engrafted, PEC-01 cells can mature into glucose-responsive insulin producing cells in patients with type 1 diabetes. To accelerate and expand its efforts, ViaCyte has established collaborative partnerships with leading companies including CRISPR Therapeutics and W.L. Gore & Associates. ViaCyte is headquartered in San Diego, California. The Company also has a robust intellectual property portfolio, which includes hundreds of issued patents and pending applications worldwide. ViaCyte is funded in part by the California Institute for Regenerative Medicine (CIRM) and JDRF. For more information on ViaCyte, please visit http://www.viacyte.comand connect with ViaCyte on Twitter, Facebook, and LinkedIn.

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SOURCE ViaCyte, Inc.

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Scientists Uncover Ways HIV is Sexually Transmitted in Women – PRNewswire

Posted: May 28, 2020 at 3:46 am

A team of scientists at Gladstone Institutes and UCSF recently uncovered unique properties of immune cells from women's reproductive tissues that, together with HIV molecular tricks, facilitate the virus's spread in a woman's body. Their findings, published in eLIFE, could inform the design of preventive drugs specially tailored for women.

"Our studies reveal intriguing strategies potentially used by HIV to evade the immune system and spread throughout the woman's body," says Nadia Roan, PhD, a visiting scientist at Gladstone who led the study. "Supplementing PrEP or topical microbicides with drugs that target these processes could improve the overall efficacy of prevention approaches."

Remarkably Receptive Hosts

HIV is known to home in on a special type of immune cell called a CD4+ T cell. These cells are found in many tissues, including the lining of the female reproductive tract, and their properties vary depending on their tissue of residence.

"We still lack a fundamental understanding of the features of cells that first become infected upon HIV transmission in women," says Roan, who is also professor of urology at UC San Francisco."This is partly because cells in the female reproductive tract, unlike those circulating in the blood, are difficult to access."

Roan's team obtained cells of the female reproductive tract from biopsy specimens. They exposed the cells to HIV in the lab to identify the likely targets of the virus in this part of the woman's body. In parallel, the scientists conducted the same infections on blood cells and cells from tonsil biopsies.

While T cells from all three sources became infected by the virus, those from the female reproductive tract were up to 100 times more susceptible to infection than the other cells.

"What's intriguing is that T cells in the female reproductive tract seemed naturally primed to become infected by HIV," says Roan. "While T cells from blood require an extra boostcalled activationto become infected by HIV in the lab, those in the female reproductive tract did not."

Remodeled by the Invader

It is difficult to pinpoint HIV's target cellsin the female reproductive tract and elsewherebecause the virus remodels its host cell after infection. For instance, upon entering a CD4+ T cell, HIV removes the CD4 protein from the cell surface, so the cell no longer looks like a CD4+ T cell.

CD4 is just one of a plethora of proteins a T cell puts on its surface. These proteins serve as the cell's identification card; different cell types have different surface protein profiles, and scientists use these profiles to identify the types of cells present in a tissue or a lab culture.

But because of HIV's remodeling, by the time scientists examine an infected cell, they can't tell whether its surface proteins reflect the cells' original identity or a new identity crafted by the virus.

A few years ago, Roan and her team developed a wayto circumvent this problem.

"The virus does not change all the proteins in the cells it infects," says Tongcui Ma, PhD, a postdoctoral researcher in Roan's lab and the first author of the study. "We have a way to monitor a large number of proteins, allowing us to find some that remain unchanged after infection."

These unchanged proteins reveal the identity of the virus's initial targets. By the same token, the scientists also learn what processes the virus remodeled in these cells.

HIV's AgendaSurvive and Spread

Roan's team found that HIV's preferred targets in the female reproductive tract do share some traits with HIV's targets in other tissues. They belong to a class of CD4+ T cells called effector memory cells, which remember previous infections and help fight them off during future encounters.

However, the female reproductive tract cells also display distinctive characteristics compared to blood cells, in particular a high amount of the CCR5 protein on their surface. This protein serves as one of HIV's gateways into cells, and its abundance on the surface of T cells in the female reproductive tractprobably explains their high susceptibility to infection.

In addition, the scientists found that a greater variety of T cells appear susceptible to infection in the female reproductive tract samples than in blood samples, which would further help HIV take hold in this tissue.

"We discovered that after infection, T cells in the female reproductive tractdisplay higher amounts of surface proteins known to guide cells toward lymph nodes, which in turn harbor many of the types of cells HIV can infect," says Ma. "We believe this mechanism may help HIV exit the female reproductive tract and enter the lymphatic system, enabling the eventual systemic spread of the virus throughout the woman's body."

Roan's team uncovered other modifications made by HIV that seem aimed at increasing the virus's ability to persist in the face of an active immune system. Infected cells had lower levels of surface proteins that normally help them respond to pathogens. This would cripple their ability to mount a proper defense against invaders, including HIV.

The virus also increased the cells' production of a protein called BIRC5, which protects cells from untimely death. In fact, not only did the virus increase BIRC5, it also seemed to preferentially target cells with higher than average stores of BIRC5.

"Overall, our study suggests that the female reproductive tract is poised for remarkably efficient HIV infection and dissemination," says Roan. "Our findings mayhelp explain the inconsistent effectiveness of oral PrEP or microbicides in protecting women from sexual transmission of HIV."

Scientists can now use these findings to develop strategies that could stem the ability of sexually transmitted HIV to infect women. Roan and her team have already found that a clinically-tested inhibitor of BIRC5 can block HIV's ability to promote the survival of female reproductive tract cells infected in the lab.

"We hope that complementing current interventions with drugs that target features of T cells in the female reproductive tractthat make them particularly susceptible to HIV will improve the outcome for women," says Roan.

About the Research Project

Other authors include Xiaoyu Luo and Warner C. Greene from Gladstone Institutes, Gourab Mukherjee from University of Southern California, Nandini Sen from Stanford School of Medicine, Trimble Spitzer from Naval Medical Center,and Ashley F. George and Linda C. Giudice from UC San Francisco.

This work was supported by multiple institutes or centers from the National Institutes of Health (R01 AI127219, R01 AI147777, P01 AI131374, P30 DK063720, S10 1S10OD018040, S10 RR028962, and P30 AI027763).

About the Gladstone Institutes

To ensure our work does the greatest good, Gladstone Institutesfocuses on conditions with profound medical, economic, and social impactunsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with the UC San Francisco.

Media Contact: Megan McDevitt | VP Communications | [emailprotected] | 415.734.20191650 Owens Street,San Francisco, CA94158 |gladstone.org|@GladstoneInst

SOURCE Gladstone Institutes

https://gladstone.org

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Startup targets glioblastoma tumors with CAR-T therapy – FierceBiotech

Posted: May 28, 2020 at 3:43 am

One of the major breakthroughs in cancer treatment is CAR-T technology, which involves genetically modifyinga patients own immune cells so they can recognize and attack cancer. But while the innovationhas benefited patients with certain blood malignancies, progress in solid tumors remains limited.

Now, scientists at McMaster University and the University of Toronto have developed a CAR-T therapy for the aggressive brain cancer glioblastoma. It helped reduce tumor burden and improved survival in mouse models, according to a new study published in the journal Cell Stem Cell.

The researchers were so encouraged by the findings that they launched a startup called Empirica Therapeutics, which aims to bring the CAR-T drug into clinical trials in recurrent glioblastoma patients by 2022.

For each CAR-T construct, T cells are modified to produce a special structure called a chimeric antigen receptor (CAR) that gives the cells the ability to recognize a specific protein on cancer cells. The two FDA-approved CAR-Ts, Novartis Kymriah and Gilead Sciences Yescarta, are directed toward CD19. TheCAR-T cell Empirica is developing targets CD133, also known as prominin-1.

In a 2003 Cancer Research study, a McMaster University team identified a group of neural stem cells from human brain tumors that bear CD133 on their surface. They found these CD133-expressing cells could differentiate into cells identical to the original tumor, suggesting these stem cells are necessary for glioblastoma tumor growth.

For the current study, the team tested three types of treatments in lab dishes and in mice. The first was a human IgG antibody that binds to CD133 on glioblastoma cells. The second was a bispecific T-cell engager antibody (BiTE), which can recruit cytotoxic T cells to kill tumor cells. The third was the CAR-T, known at Empirica as eCAR-133.

We found that the CAR-T therapy had enhanced activity compared to the other two therapeutics in preclinical models of human glioblastoma, Parvez Vora, the studys first author and director of preclinical development at Empirica, said in a statement.

Moreover, the CAR-T drug didnt induce any acute systemic toxicity in mice, showing it wouldnt disrupt hematopoiesis, a vital process in the human body that leads to the formation of blood cells, Vora said.

RELATED:Killing brain tumors with CAR-Ts built with scorpion venom

The potent clinical responses from CAR-T cells in blood cancers have sparked interest in exploring the approach in solid tumors, including hard-to-treat glioblastoma. A research team at City of Hope recently designed a novel CAR based on chlorotoxin, a toxin found in scorpion venom, and recorded promising results of the CAR-T cells in mice with glioblastoma xenografts.

There are many obstacles ahead. For one thing, the glioblastoma tumor microenvironment is notoriously immunosuppressive, which could dampen CAR-T cells activity once they arrive at the tumor site.

Besides CD133, other glioblastoma CAR-T targets that have been floated include IL-13Ra2 from City of Hope researchers, CSPG4froma team at the University of North Carolina, NKG2DL and EGFRvIII, among others.One possibility could be a combo of CAR-T and BiTEtechnologies. Last year, a team led by Massachusetts General Hospital designeda CAR-T that also expressed BiTE to activate bystander T cells against tumors. The CAR-T/BiTE cells eliminated tumors in mouse models of glioblastoma.

The Empirica scientists are also exploring combination strategies for their CD133-targeting CAR-T to treat glioblastoma."We hope that our work will now advance the development of really new and promising treatment options for these patients," said co-author Sheila Singh, professor in the department of surgery at McMaster and CEO of the startup.

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Researchers develop nanoengineered bioink to 3D print functional bone tissue – 3D Printing Industry

Posted: May 27, 2020 at 9:45 am

Scientists in the Department of Biomedical Engineering at Texas A&M University are seeking to advance the field of 3D bioprinting functional tissues, by conducting research into the development of new biomaterials.

Dr. Akhilesh K. Gaharwar, an associate professor in the department, has created a highly 3D printable bioink, which can be used as a platform for generating anatomical-scale functional tissues. The new material developed by Gaharwars research group, known as Nanoengineered IonicCovalent Entanglement (NICE) bioink, has been designed to overcome the deficiencies of current bioinks in relation to structural stability. Commenting on the benefits of the NICE bioink, Gaharwar states: The next milestone in 3D bioprinting is the maturation of bioprinted constructs toward the generation of functional tissues.

Our study demonstrates that NICE bioink developed in our lab can be used to engineer 3D-functional bone tissues.

Bioprinting bone tissue

In their study, Gaharwars research group first outlined the emergence of 3D bioprinting as a technique for fabricating patient-specific, implantable constructs for regenerative medicine. Using hydrogels and combining them with cells and growth factors, these bioinks are 3D printed to create tissue-like structures intended to imitate the function of natural tissues.

One particularly useful application of the technology is in patient-specific bone grafting, a surgical procedure that replaces missing bone in order to repair bone fractures. As traditional treatments for managing bone defects and injuries are slow and expensive, Gaharwar states that developing replacement bone tissues with bioprinting could create exciting new treatments for patients. These can be used to treat defects and conditions such as arthritis, bone fractures, dental infections and craniofacial defects.

Recent advancements in the field have come from Rice University and the University of Maryland (UMD). Scientists at these institutions have outlined a new proof-of-concept for 3D printing artificial bone tissue to help repair damage related to arthritis and sporting accidents.

In late 2019 onboard the ISS, 3D Bioprinting Solutions, a Russian bio-technical research laboratory, 3D bioprinted bone tissue in zero gravity. Leveraging its Organ.Aut 3D bioprinter, the labs researchers hope to one day create real bone implants for astronaut transplantation on long interplanetary missions.

Nanoengineered bioinks for stronger bone structures

In the bioprinting process, cell-laden biomaterials flow through a nozzle in liquid form, however immediately solidify as soon as theyre deposited. It is necessary for bioinks to act as cell carriers and structural components, which requires them to be highly printable while providing a robust and cellfriendly microenvironment.

As outlined in the research paper, Gaharwars team explain that current bioinks in use lack the sufficient biocompatibility, printability, structural stability and tissuespecific functions needed for preclinical and clinical applications of bioprinting. The potential applications of bioprinting have been limited due to the lack of bioinks capable of meeting the demands of both 3D printing and tissue engineering. For example, ideal bioinks must be capable of extruding into stable 3D structures, while also protecting cells during and after printing, and providing an appropriate environment that can be remodeled into the target tissue. Unfortunately, conventional hydrogels are weak and poorly printable, explain the authors.

In response to this issue, Gaharwars research group has developed the NICE bioink formulation specifically for 3D bone bioprinting. NICE bioinks are a combination of two reinforcement techniques (nonreinforcement and ionic-covalent network). Used together, they provide an effective reinforcement that results in much stronger bone structures. Explaining the benefits of the material, the researchers write: The NICE bioinks allow precise control over printability, mechanical properties and degradation characteristics, enabling custom 3D fabrication of mechanically resilient, cellularized structures.

Once the bioprinting process is complete, the cell-laden NICE networks are crosslinked to form stronger scaffolds. Using this technique, Gaharwar and his team have been able to produce full-scale, cell-friendly reconstructions of human body parts, including ears, blood vessels, cartilage and bone segments.

In their tests, the researchers found that the enclosed cells began depositing new proteins containing a cartilage-like extracellular matrix that subsequently calcifies to create a mineralized bone over a three-month period. Five percent of these 3D bioprinted scaffolds consisted of calcium, which is similar to cancellous bone, the network of spongy tissue typically found in vertebral bones.

Gaharwars research group used a genomics technique called whole transcriptome sequencing (RNA-seq) to examine how these bioprinted structures were able to induce stem cell differentiation. RNA-seq works by capturing a snapshot of all genetic communication inside the cell at a given moment. The team worked with Dr. Irtisha Singh, assistant professor at the Texas A&M Health Science Center, who served as a co-investigator.

Using their bioink and research results, Gaharwars team plans to demonstrate in vivo functionality of the 3D bioprinted bone tissue.

The study, Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue is published in ACS Applied Materials & Interfaces. It is written by David Chimene, Logan Miller, Lauren M. Cross, Manish K. Jaiswal, Irtisha Singh, and Akhilesh K. Gaharwar.

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Featured image shows Dr. Akhilesh Gaharwar. Photo via Texas A&M Engineering.

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New method provides unique insight into the development of the human brain – Science Codex

Posted: May 26, 2020 at 8:45 pm

Stem cell researchers at Lund University in Sweden have developed a new research model of the early embryonic brain. The aim of the model is to study the very earliest stages of brain to understand how different regions in the brain are formed during embryonic development. With this new insight, researchers hope to be able to produce different types of neural cells for the treatment of neurological diseases more efficiently. The study is published in the journal Nature Biotechnology.

In order to develop stem cell treatments for neurological diseases such as Parkinson's Disease, epilepsy and stroke, researchers must first understand how the human brain develops in the embryonic stage. With knowledge of how neural cells are formed at different developmental stages, researchers have the opportunity to develop new stem cell therapies more quickly in the laboratory.

"The challenge is that there are thousands of different sub-types of neural cells in the human brain, and for each disease we need to be able to produce exactly the right type of neural cell", says Agnete Kirkeby, researcher at the Wallenberg Centre for Molecular Medicine and the Department of Experimental Medical Science at Lund University.

Studies on how each individual neural cell forms in the embryo during brain development are essential for the researchers to be able to understand how to produce these specific cells in the laboratory.

Research on the early development of the human brain, from five days after the fertilisation of the cell to approximately seven weeks, have so far been difficult as researchers have not had access to human embryonic tissue from these early stages of development. Therefore, nearly all knowledge of the earliest development of the brain is based on studies in flies, chickens and mice.

"However, the composition of the human brain differs greatly from the animals' brains. Therefore, this period in the development of the human brain has long been viewed as the black box of neurology", says Agnete Kirkeby.

Together with colleagues from the University of Copenhagen and bioengineers Thomas Laurell and Marc Isaksson from the Faculty of Engineering at Lund University, Agnete and her team have now created a model that mimics the early developmentalstages of the human brain through the use of stem cells. The stem cells are cultivated in a custom-built cell culture chamber where they are exposed to an environment which resembles the environment in the early embryonic brain.

"In the laboratory model called MiSTR (Microfluidic-controlled Stem cell Regionalisation), we can create tissue that contains different brain regions next to each other, similar to an embryonic brain approximately four to five weeks after fertilisation."

"We start with a small group of cells that will form the brain and instruct the cells by exposing them to a gradient of a specific growth factor (WNT) so that they form different regions of the brain. Our model is better than previously published models because it is much more reproducible and contains more brain regions. We can now use it to study unknown characteristics in the early development of the human brain", explains Agnete Kirkeby.

Agnete Kirkeby believes that the new method may be used to investigate how brain cells in the early embryonic stages react to certain chemicals surrounding us in our daily lives

"This is a significant step forward for stem cell research. For the first time, we now have access to tissue that resembles the early embryonic brain and can therefore study processes behind brain development in a way that has not been possible before. We can for instance use it for testing how chemical substances in our environment might impact on embryonic brain development." explains Kirkeby.

Another aim for the future is to use the model to create a complete map of the development of the human brain. This will help to speed up the development of new stem cell treatments for neurological diseases.

"Once we have the map we will also become better at producing human neural cells in the laboratory that could be used for transplantations, regenerative therapy and to study the brain's function as well as different disease states. . It took us ten years to develop a stem cell treatment for Parkinson's disease because our methods were dependent on trial and error. Our goal is that this process will be much faster in the future for other diseases", concludes Agnete Kirkeby.

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