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Xiling Shen: An Engineering Approach to Biomedical Challenges

Posted: February 24, 2015 at 1:57 pm

Using engineering principles to understand the complexity of stem cells and cancer

Xiling Shen will join the biomedical engineering department in Duke Universitys Pratt School of Engineering in July 2015. An electrical circuit and computer systems expert by training, Shen applies his engineering background to understand the complex regulatory networks behind biological systems and diseases.

Medical research has long taken a reductionist approach to health care, Shen said. For example, researchers often focus on finding the culprit protein that gives rise to a disease, so that the protein can be targeted to produce a cure. Many challenging diseases such as cancer, however, are caused by complex interactions among a network of many proteins and RNAs as well as changes to their physical environmentwhich cant be fully understood outside of that context.

Xiling Shen

We need better computer and animal models that accurately reproduce the complexity of biological systems and human diseases, said Shen, who joins Duke from Cornell University. Better models can better recapitulate the physiological environments seen by our own cells, which produce better studies and results.

Shen earned his bachelors, masters and doctorate degrees from Stanford University, before conducting postdoctoral research at the University of CaliforniaBerkeley. He then joined Cornell Universitys faculty as an assistant professor of electrical and computer engineering and biomedical engineering in 2009. He also worked as an analog and wireless circuit designer at Barcelona Design and Texas Instruments between 2001 and 2004.

One example of Shens work is a recent study that revealed for the first time that small RNAs called microRNAs instruct cancer stem cells to divide in two different ways. Besides a division process that results in two cancer stem cells, his laboratory discovered that they can also divide into one cancer stem cell and one tissue cell. This allows tumors the flexibility to grow while maintaining a steady supply of stem cells. Such microRNAs can be therapeutically target to disrupt tumor growth.

Another recent study discovered that cancerous cells hijack mechanisms originating in the immune system to catch a ride to different organs during metastasis. Leveraging this discovery, Shens laboratory injected engineered human cancer cells into mouse embryos. These mice grew up recognizing human cancer cells as their own, which led to the growth of human tumors in the organs where they would naturally occur.

In the past, cancerous human cells have just been injected under the skin of mice to grow tumors for testing, said Shen, who hopes that realistic disease models will enable researchers to find better cancer drugs that have been elusive so far. But that microenvironment is completely different from those of various organs, and that can play a huge role in how well the tumor grows and how well treatments work. Genetically engineering switches into cancerous cells to direct them to the proper organ will provide a more accurate model for testing.

Shen sees the close physical proximity and institutional ties between Duke Medicine and the biomedical engineering department as a potential boon for his research. As an engineer, Shen says he isnt satisfied with simply discovering new things; he wants to take his work from bench to bedside to have a large societal impact.

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Jakub Tolar, M.D., Ph.D. – MED – Stem Cell Institute …

Posted: February 24, 2015 at 1:54 pm

Institute Director

tolar003@umn.edu

Education

Dr. Tolar is an Associate Professor of Pediatrics at the University of Minnesota in the Division of Blood and Marrow Transplantation, and an attending physician at the University of Minnesota Amplatz Childrens Hospital Fairview. Dr. Tolar is trained both in basic science and in medicine. He received his M.D. from Charles University in Prague, Czech Republic, and his Ph.D. in Molecular, Cellular, Developmental Biology and Genetics from the University of Minnesota. He completed a residency in Pediatrics and a fellowship in hematology/oncology and bone marrow transplantation at the University of Minnesota. He is board certified in Pediatric Hematology/Oncology. Dr. Tolar has been the Director of Stem Cell/Gene Therapies in the Division of Blood and Marrow Transplantation since 2011.

Dr. Tolar's research focuses on stem cell therapy for patients with lethal diseasescancer, inborn errors of metabolism, and devastating genetic disorders.

Research Interests

In the laboratory, he is currently working on inducing pluripotency in a variety of cell types and creating human disease models in a dish at the cellular level. He is also investigating gene editing using sequence-specific nucleases. Dr. Tolars primary motivation is improving patient care and the clinical translation of tissue stem cell and regenerative biology. He has several clinical trials that focus on the efficacy and safety of new treatments for diseases like epidermolysis bullosa and dyskeratosis congenita. He also leads the International Fanconi Anemia Gene Therapy Working Group.

Selected Recent Publications

Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, Chen M, Osborn MJ, Lund T, Dolan M, Blazar BR, Tolar J. N Engl J Med. 2010;363(7):629-39.

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Stem Cell Research – Right to Life of Michigan

Posted: February 24, 2015 at 1:53 pm

Embryo Adoption: A Tale of Twins

For adopted twins Meredith and Mason Bonnema, fall of 2008 represents life and a future for both. Their adoptive parents were finalizing plans to welcome them to their new family.

Meredith and Mason were too small to remember that fall, because they were both smaller than the period at the end of this sentence. They spent the first few months of their adoption in deep freeze, waiting for their chance as embryos to be implanted in their adoptive mother, Kari. Transferred the following February, Meredith and Mason were born in October 2009, about one year after being adopted. While their parents were eagerly waiting for them to become part of their family, a completely different plan was being drawn up for other frozen embryos like Meredith and Mason. Voters in Michigan narrowly approved Proposal 2 in November 2008, allowing embryos to be legally destroyed for experimentation. FULL STORY

The birth of a child is always special, but now with the donation of cord blood -- a baby's birth can also give life to others. Cord blood banks help ensure that patients suffering from a variety of blood ailments have the opportunity to receive a transplant of life-affirming stem cells from umbilical cord blood. MORE

The Great Stem Cell Debate: Understanding the Basics As the debate over stem cell research rages on, Right to Life of Michigan has put together a fact sheet discussing basic information about the issue and the difference between adult stem cells and embryonic stem cells. PDF

Sacrificed Without Consent: Taking From the Unborn, Ending Lives Since stem cells are so versatile there is hope within the medical community that some day the cells can be reprogrammed to cure various diseases. This stem cell fact sheet contains information on the potential of stem cells, stem cell research, and the current legal situation regarding embryonic stem cell research. HTML | PDF

Cloning: No Longer Science Fiction

As we stand at a time when technology is quickly advancing, researchers have begun to bombard our nation and the rest of the world with questions of how far science can and should go. Since the pursuit of scientific breakthroughs and discoveries continues unfettered, our world is continually threatened with attacks on the sanctity of human life. PDF

Many people are nervous about giving blood. The thought of anything related to a needle is enough to make their hair stand on end. There is one way, however, to give a potentially life saving blood gift without suffering any anxiety.

"It's an easy thing," said Mary Sumners of Grand Rapids. "It's super easy to do. I don't usually give blood, so it was a great way to give something." This easy thing is donating umbilical cord blood after childbirth. Cord blood is a rich source of adult stem cells. FULL STORY

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Stem Cell Biology and Regenerative Medicine | Brown University

Posted: February 24, 2015 at 1:49 pm

Pre College Catalog Stem Cell Biology and Regenerative Medicine

Return to Course Catalog

There's a lot of controversy surrounding embryonic stem cells, but did you know that there are many types of stem cells in the body and that some are already being used to treat diseases? In this course, you'll learn about what stem cells are, what they do, and their importance to research and medicine. Youll even learn how to culture mammalian cells. Discover how stems cells allow a single fertilized egg to develop to into a complex human being, how they are used by doctors to help restore the immune system of cancer patients and how technological advances are helping scientists harness the power of stem cells to learn about and treat disease.

Stem cells have the remarkable ability to become any one of the 200+ cell types found in humans. This course will explore what makes stem cells unique, how they function normally in the body to create and maintain specialized organs and how they are being used in regenerative medicine. We will cover the basic cell, molecular and developmental biological principles required to understand exactly what these incredible cells are.

We will examine what stem cells do in different organ systems, how they keep us healthy, and how they can be harvested and manipulated to become different types of cells, which can be used in research and medicine. We will also learn about the phenomenal new discovery of induced pluripotent stem (iPS) cells. In iPS cells, scientists can reprogram adult cell types to become stem cells outside of the body by adding a specific set of genes. We will learn how researchers and physicians are using innovative technologies to unlock stem cells potential to treat a variety of human diseases and injuries such as blindness, diabetes, heart disease and sports injuries.

To complement classroom lectures, discussions and activities, this course will have a daily laboratory component. Students will learn the basic skills required for mammalian tissue culture. We will grow different types of cells, use biochemical techniques to alter their cellular identities and use fluorescent microscopy along with other visualization methods to observe these changes.

Upon completion of this course students will extend their knowledge from general high school biology to include an introduction to the more specialized areas of cell, molecular and developmental biology, which will be helpful when taking college courses. They will also acquire basic molecular biological laboratory skills. This will not only allow them a deeper understanding of stem cells, but it will help them distinguish between what stem cells can and cannot do in a medical context. Students will also be exposed to current applications of stem cell technology and new innovations that they will see develop in the near future.

A general high school biology class is required.

* Please Note: This course has a Supplemental Fee of $300.00

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Innovative Medicine: Pluripotent Stem Cells (Public Lecture) – Video

Posted: February 24, 2015 at 8:43 am


Innovative Medicine: Pluripotent Stem Cells (Public Lecture)
Human ES cells have been expected as suitable resources for cell transplantation therapies. However, it has sparked ethical controversy and causes immune rej...

By: Public Domain TV

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Wisdom teeth stem cells can transform into cells that could treat corneal scarring

Posted: February 23, 2015 at 3:47 pm

Stem cells from the dental pulp of wisdom teeth can be coaxed to turn into cells of the eye's cornea and could one day be used to repair corneal scarring due to infection or injury, according to researchers at the University of Pittsburgh School of Medicine. The findings, published online today in STEM CELLS Translational Medicine, indicate they also could become a new source of corneal transplant tissue made from the patient's own cells.

Corneal blindness, which affects millions of people worldwide, is typically treated with transplants of donor corneas, said senior investigator James Funderburgh, Ph.D., professor of ophthalmology at Pitt and associate director of the Louis J. Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, a joint program of UPMC Eye Center and the McGowan Institute for Regenerative Medicine.

"Shortages of donor corneas and rejection of donor tissue do occur, which can result in permanent vision loss," Dr. Funderburgh said. "Our work is promising because using the patient's own cells for treatment could help us avoid these problems."

Experiments conducted by lead author Fatima Syed-Picard, Ph.D., also of Pitt's Department of Ophthalmology, and the team showed that stem cells of the dental pulp, obtained from routine human third molar, or wisdom tooth, extractions performed at Pitt's School of Dental Medicine, could be turned into corneal stromal cells called keratocytes, which have the same embryonic origin.

The team injected the engineered keratocytes into the corneas of healthy mice, where they integrated without signs of rejection. They also used the cells to develop constructs of corneal stroma akin to natural tissue.

"Other research has shown that dental pulp stem cells can be used to make neural, bone and other cells," Dr. Syed-Picard noted. "They have great potential for use in regenerative therapies."

In future work, the researchers will assess whether the technique can correct corneal scarring in an animal model.

Story Source:

The above story is based on materials provided by University of Pittsburgh Schools of the Health Sciences. Note: Materials may be edited for content and length.

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Stem Cells from Pulled Teeth Might Yield a Cure for Blindness

Posted: February 23, 2015 at 3:47 pm

Durham, NC (PRWEB) February 23, 2015

Recent research aimed at finding a treatment for a common form of blindness could give new meaning to the term eye teeth. In a study in mice published in STEM CELLS Translational Medicine, researchers at the University of Pittsburgh show how stem cells harvested from teeth extracted during routine dental procedures can potentially be used to restore sight in those suffering from corneal blindness.

Corneal blindness afflicts millions of individuals worldwide. It occurs when the cornea becomes scarred and cloudy and light cannot penetrate the eye to reach the light-sensitive retina. Since corneal scarring is largely irreversible, the most common method of treatment is to graft a new cornea using tissue taken from cadavers. Given that there is a worldwide donor shortage and that many grafts are eventually rejected because they are not the patients own tissue, researchers have been looking for a new source for such tissue or a new way to regenerate the patients own cornea. (The current failure rate of corneal grafts is about 38 percent after 10 years, primarily due to tissue rejection.)

The University of Pittsburgh team, led by James L. Funderburgh, Ph.D., and Fatima Syed-Picard, Ph.D., both in the Department of Ophthalmology, decided to focus on adult dental pulp stem cells (DPSC) as a possible solution.

If we could generate an engineered cornea using autologous cells, which are the patients own cells, and then use that to replace scarred tissue, we could bypass the limitations of current treatments, Dr. Funderburgh explained. We thought dental pulp might be the answer, as other studies have proven that DPSCs can differentiate into various other cells and they already have a similarity to cornea tissue as they both develop in the embryo stage from the cranial neural crest, he added. That led us to believe that we might induce DPSCs to become corneal cells, too.

The team began by collecting DPSCs from molar teeth discarded after routine extractions at the universitys dental school and then treated the cells in a special solution that caused them to differentiate into corneal cells, or keratocytes. When they tested the DPSC-generated keratocytes they found they had the same properties as those grown naturally in the human eye.

They then seeded the cells onto a corneal shaped nanofiber substrate to see if they could engineer corneal tissue. Four weeks later, the cells had grown into a structure that mimicked the complex organization of an actual cornea.

Their final task was to evaluate how the DPSC-generated keratocytes would perform by labelling them with a dye (for tracking purposes) and then injecting them into the right eyes of mice. (The left eye of each animal was injected with medium only, as a control.) When they tested the mices eyes five weeks later, they found that the DPSC-generated keratocytes had remained in the corneas and behaved similar to natural keratocytes. Their corneas were clear, and there were no signs of rejection.

These studies provide promising data on the potential translation of DPSC as an autologous cell source for regenerative corneal therapies and possibly more, Dr. Funderburgh concluded.

This study provides promising data on the use of adult dental pulp cells for personalized regenerative medicine to treat corneal blindness, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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ESPERITE (Euronext ESP) pioneers first treatment worldwide of Cerebral Palsy using two types of stem cells

Posted: February 23, 2015 at 3:47 pm

CryoSave, part of ESPERITE, is the only private cord blood bank sponsoring a GCPclinical trial according to GMP-ATMP international guidelines

CryoSave leads and sponsors a multicentre clinical trial following GCP-ICHstandards, for investigation of new treatment of Cerebral Palsy using dual infusionof two types of stem cells derived from umbilical cord blood and cord tissueprocessed by CryoSave

Geneva, Switzerland - 23 February 2015

The clinical trial aims to demonstrate safety and preliminary efficacy of sequential intravenousinfusion of the ex vivo expanded mesenchymal stem cells (MSC) derived from cord tissue and thecord blood stem cells. The study will use, for the first time in clinical research, autologous MSC

derived from cryopreserved cord tissue. The clinical trial, sponsored by CryoSave, will be performedin collaboration with Professor Manuel Ramrez Orellana, the Principal Investigator, and ProfessorLuis Madero, the Clinical Supervisor from the University Hospital Nio Jesus in Madrid, Spain.

Cerebral Palsy is a devastating disease diagnosed in 1 per 326 children according to CDC, with noavailable treatment. 17 Million people worldwide live affected by cerebral Palsy (CPIRF). 26 BillionUSD are spent every year to accommodate the life of these patients in the US (WHO).

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TiGenix: TiGenix's Phase III trial design for Cx601 endorsed by President-Elect of ECCO

Posted: February 23, 2015 at 3:47 pm

PRESS RELEASE

TiGenix's Phase III trial design

for Cx601 endorsed by President-Elect of ECCO

Leuven (BELGIUM) - 23 February, 2015 -TiGenix NV (Euronext Brussels: TIG), an advanced biopharmaceutical company focused on developing and commercialising novel therapeutics from its proprietary platform of allogeneic expanded adipose-derived stem cells in inflammatory and autoimmune diseases, announced today that Dr Julian Pans, a leading clinical specialist in inflammatory bowel disease, endorsed the design of the Company's Phase III trial of Cx601 for the treatment of complex perianal fistulas in patients with Crohn's disease during his presentation last week at the 10th Annual Congress of the European Crohn's and Colitis Organisation (ECCO) held in Barcelona, Spain.

Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASCs) delivered locally through intra-lesional injection that is being developed for the treatment of perianal fistulas in Crohn's disease patients. Such fistulas cause severe complications and are difficult to manage, and have a significant negative impact on patient quality of life and psychological well-being. There is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognising the debilitating nature of the disease and the lack of treatment options.

TiGenix is conducting a randomised, double-blind, placebo-controlled Phase III trial in Europe and Israel designed to comply with the requirements laid down by the European Medicines Agency (EMA). This pivotal study, codenamed 'ADMIRE', has recruited 289 patients across 52 centres in 7 European countries and Israel. The results of the study will be available in the third quarter of 2015 and, if positive, will allow TiGenix to submit a request for marketing authorisation to the EMA early in 2016.

Dr. Julian Pans, who is Head of the Gastroenterology Department, Head of the Inflammatory Bowel Diseases Unit, and Associate Professor of Medicine at the Hospital Clnic of Barcelona, President-elect of ECCO and Chairman of the TiGenix ADMIRE Scientific Advisory Board, made his comments during a presentation last week at the Annual Congress of ECCO in a session entitled, 'Mesenchymal Stem Cells in Inflammatory Bowel Disease: promises and pitfalls'.

"I strongly believe that there are not in general adequately designed and controlled studies of the role of stem cells in the treatment of perianal fistulas in Crohn's disease patients," Dr. Panes said. "In the pivotal Phase III ADMIRE trial of TiGenix, we finally have the robust, controlled study that we have been waiting for."

"The positive evaluation of our Phase III study by Dr. Pans is strong recognition of the quality of our study design", commented Dr. Marie-Paule Richard, Chief Medical Officer at TiGenix. "We remain committed to bringing this new treatment to the thousands of patients who suffer from this debilitating condition".

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Europe Approves Holoclar, the First Stem Cell-Based Medicinal Product

Posted: February 23, 2015 at 3:40 pm

PARMA and MODENA, Italy, February 23, 2015 /PRNewswire/ --

The collaborationbetween a public excellent researchcenteranda solidprivate pharmaceuticalcompany allowed toachievean extraordinary result, entirely "made in Italy":the first medicinal productcontainingstem cellsapproved in the Western world

The European Commission has granted a conditional marketing authorization, under Regulation (EC) No 726/2004, to Holoclar, an advanced therapy based on autologous stem cells and capable to restore the eyesight of patients with severe cornea damage. Holoclar is manufactured by Holostem Terapie Avanzate (HolostemAdvanced Therapies) - a spin-off of the University of Modena and Reggio Emilia - at the Centre for Regenerative Medicine "Stefano Ferrari" (CMR) of the same University.

(Logo: http://photos.prnewswire.com/prnh/20150223/731609-a )

(Logo: http://photos.prnewswire.com/prnh/20150223/731609-b )

(Logo: http://photos.prnewswire.com/prnh/20150223/731609-c )

"Holoclaris theveryfirstmedicinalproductbased onstem cellsto beapproved andformallyregisteredin the Western world," states AndreaChiesi, Director of R&D Portfolio Management of Chiesi Farmaceutici S.p.A. and CEO of Holostem Terapie Avanzate. "This record," continues AndreaChiesi,"shows that thepartnershipbetween the public and privatesectorsis not only possible,butisprobably the best strategy for the development of stem cell-based regenerative medicine, particularly when autologous cells are used.Holostemisnowconsideredasabusiness modeltotranslate into clinicstheresultsobtained byscientific researchin this field." Underlying Holoclar are more than 20 years of excellence in research, conducted by a team of internationally renowned scientists in the field of epithelial stem cell biology aimed at clinical translation. European Directive 1394/2007 substantially equalizes advanced cell therapies to medicines and imposes, among other things, that cell cultures has to be manufactured only in GMP-certified facilities (GMP: Good Manufacturing Practice). Thanks to the investments of Chiesi Farmaceutici, the Centre for Regenerative Medicine in Modena - where Holostem operates - was certified as GMP compliant and continue to follow the path towards the registration of this newly developed advanced therapy.

"The authorization processhas been long andcomplex, butthe resultachievedtodayshows thatcellscan beculturedaccording topharmaceutical standardsappropriateto guaranteesafety and efficacy," adds Professor MicheleDeLuca, Scientific Director and co-founder of Holostem, as well as Director of the CMR of the University of Modena. "In addition,ina periodof great confusionabout the realtherapeutic possibilitiesof stem cells,such as the onewe are living in, being ableto demonstratethatstem cells can be definitely safe and successful in a controlled clinical settingismore important than ever." To explain how Holoclar works is Professor GraziellaPellegrini, Coordinator of cell therapy at CMR, as well as director of R&D and co-founder of Holostem, who authored, together with Professor De Luca, the research and designed the product development: "Afterdevelopingcell culturesbased onepithelial stem cellsfor the treatmentofvariousdisorders ofthestratifiedepithelia-from the skinfor full-thicknessburnsto the reconstructionof the urethra-wediscoveredthatthe stem cellsthat allowthe regenerationof the cornearesidein asmall areaatthe borderbetween the cornea(the transparent partat thecenter of the eye)andthe conjunctiva(the contiguous white part),which is called'the limbus'.Whenthermal or chemicalburnsof theocular surfacedamageirreversiblythisstemcellreserve,thecorneal surface-whichin ahealthy eyecompletely renews itself approximatelyeverysix/ninemonths-stopsregeneratingand the conjunctivagraduallybegins tocover thecorneawithawhite coating,thatprevents visionand causes chronicpainandinflammation.Ifinat leastone of the eyes of the patientevenasmallresidueofundamaged limbus is left,we areable to reconstructin a laboratorythe epitheliumthat covers thecorneal surface,thanks to thestem cells harvestedthrough a 1-2mmbiopsy.Thisgraftofepithelium-Holoclar, precisely-that looks likea kind ofcontactlens,is thentransplantedinto the patientandallows to obtain along-termtransparent corneaanda full recoveryof visual acuity,without causing anyrejection reaction,because itconsists of cellsof the patient him/herself."

This therapy, experimentally applied for the first time in humans in the nineties, and designated as orphan drug in 2008, thanks to the registration obtained today, in the near future will be available to all European patients who have suffered workplace injuries (caused, for example, by burnt lime, solvents or acids), domestic accidents (for example eye burns caused in adults and children by detergents or abrasive agents) or - as unfortunately reported by the press in the past few months - in the cases of assault with chemical agents.

Meanwhile, the research in Modena does not stop. The next goal of the team of Emilian researchers and entrepreneurs is to develop new advanced therapy products, such as the gene therapy for the treatment of epidermolysis bullosa, or "Butterfly disease", to date used successfully in the first two patients ever. And to develop new experimental and clinical protocols using different stem cells of stratified epithelia, such as conjunctiva, urethra, oral mucosa and respiratory epithelia.

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