Category Archives: Stem Cells

Vanderbilt University researchers have reported the counterintuitive discovery that certain chemotherapeutic agents used to treat tumors can have the opposite effect of tissue overgrowth in normal, intact mammary glands, epidermis and hair follicles. The researchers also are the first to report the discovery of an innate immune signaling pathway in fibroblaststhe spindle-shaped cells responsible for wound healing and collagen productionthat causes cells to proliferate. Such signaling pathways previously were attributed only to immune cells.

The article describing the research, DNA Damage Promotes Epithelial Hyperplasia and Fate Mis-specification via Fibroblast Inflammasome Activation, was published in the journal Developmental Cell on Oct. 13.

The findings of this work, led by postdoctoral fellow Lindsey Seldin and Professor and Chair of the Department of Cell and Developmental Biology Ian Macara, have broad implications for diseases associated with the immune system like psoriasis, as well as cancer and stem cell research.

Understanding the functionality of stem cells and the way that their behavior is regulated has been a longstanding research interest for Seldin. Normal stem cells have an amazing ability to continuously divide to maintain tissue function without forming tumors, she explained. We wanted to understand what happens to these cells in their native environment when subjected to damage, and if the response was connected to a specific tissue.

By testing perturbations to the epidermis, mammary gland and hair follicles vis--vis mechanical damage or DNA damage through chemotherapeutic agents, the researchers saw a paradoxical response: Stem cells, which otherwise would divide slowly, instead divided rapidly, promoting tissue overgrowth.

When the tissues were subjected to DNA damage, their stem cells overly proliferated, giving rise to different cells than they normally would. This was a very perplexing result, said Seldin, the papers lead author. We were determined to figure out if this was a direct response by the stem cells themselves or by inductive signals within their environment. The key clue was that stem cells isolated from the body did not behave the same way as in intact tissuean indication that the response must be provoked from signals being sent to the stem cells from other surrounding cell types.

The investigators turned their attention to fibroblasts, the predominant component of the tissue microenvironment. When fibroblasts in the epidermis were removed, the stem cell responsiveness to DNA damage was diminished, indicating that they played an important role. RNA sequencing revealed that fibroblasts can signal by way of inflammasomescomplexes within cells that help tissues respond to stress by clearing damaged cells or pathogens, which also in this case caused stem cells to divide. This is an astounding discovery, said Macara. Inflammasome signaling has previously been attributed only to immune cells, but now it seems that fibroblasts can assume an immune-like nature.

Seldin intends to replicate this work in the mammary gland to determine whether fibroblasts initiate the same innate immune response as in the epidermis, and more broadly how fibroblasts contribute to the development of cancer and other diseases associated with the immune system.

This work was supported by NCI/NIH grants R35CA132898, F32CA213794 and T32CA119925, as well as American Cancer Society grant PF-18-007-01-CCG.

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Vanderbilt researchers make counterintuitive discoveries about immune-like characteristics of cells, chemotherapys impact on tissue growth -...

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US scientists have discovered that a specific type of molecule may stimulate stem cells to regenerate, reversing the inflammation caused by periodontal disease.

The current treatment for periodontal disease involves opening the infected gum flaps and adding bone grafts to strengthen the teeth.

But in research published inFrontiers in Immunology, scientists from the Forsyth Institute in Massachusetts have discovered that a specific type of molecule may stimulate stem cells to regenerate, reversing the inflammation caused by periodontal disease.

This finding could lead to the development of new therapeutics to treat a variety of systemic diseases that are characterised by inflammation in the body.

For the study, the team removed stem cells from previously extracted wisdom teeth and placed the stem cells onto petri dishes. They then created a simulated inflammatory periodontal disease environment in the petri dishes. Next, they added two specific types of synthetic molecules called Maresin-1 and Resolvin-E1, both specialised pro-resolving lipid mediators from omega-3 fatty acids.

The scientists found that Mar1 and RvE1 stimulated the stem cells to regenerate even under the inflammatory conditions.

Both Maresin-1 and Resolvin-1 reprogrammed the cellular phenotype of the human stem cells, showing that even in response to inflammation, it is possible to boost capacity of the stem cells so they can become regenerative, Dr Alpdogan Kantarci said.

This finding is important because it allows scientists to identify the specific protein pathways involved in inflammation. Those same protein pathways are consistent across many systemic diseases, including periodontal disease, diabetes, heart disease, dementia, and obesity.

Now that we understand how these molecules stimulate the differentiation of stem cells in different tissues and reverse inflammation at a critical point in time, the mechanism we identified could one day be used for building complex organs, Dr Kantarci said.

There is exciting potential for reprogramming stem cells to focus on building tissues.

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How changing the stem cell response to inflammation may reverse periodontal disease - Bite magazine

Every 20 minutes someone in the UK is diagnosed with blood cancer and the register of stem cell donors who are needed to save thousands of patients lives does not currently meet the demand. Only 1 in 3 patients will find a donor match within their family and so every year over 2,000 people in the UK are left searching for a matching blood stem cell donor each year.

Blood cancer patients from Black, Asian or minority ethnicity groups face lower survival odds due to the lack ofdonordiversity. These patients have just a 20% chance of finding the best possible stem cell donor match, compared to 69% for northern European backgrounds.

This is due in part to the low numbers of donors registered from those Black, Asian or ethnic minority backgrounds. Donors from minority ethnic backgrounds make up just 13.1% of the UK stem cell register and because Black, Asian or ethnic minority patients tend to have more varied tissue meaning there is an even more specific biological requirement needed of a donor than for a white patient.

The global pandemic has made this situation even worse. Only 2% of stem cell registrations with DKMS came from black people during lockdown, falling by 20% compared to the same time the previous year.

Vaughn Scott is a patient who received a lifesaving donation from a stranger.

Vaughn Scott (34 years old) lives in Bristol and is grateful to the generous stranger who helped save his life. Theyve given him more time with his two children and the chance to marry his now wife last summer in a beautiful ceremony. Vaughn was incredibly fit and active, playing all kinds of sports and serving in the Navy. It was whilst on deployment across the world that he was urgently flown back to the UK and shockingly diagnosed with acute lymphoblastic leukaemia (ALL).

Vaughn said:

Hearing the diagnosis was the biggest blow Ive ever heard. My mind raced straight to my children and partner. When we learnt there was a way I could go into remission, I was excited that there was a way I could get better but very nervous too. With no family members as a match, all my faith was in a complete stranger that may have registered as a potential stem cell donor. Thankfully my match was found, Im now married and enjoying life with my family and Im so grateful. So many people arent as lucky as me. If you can, please register and give other people the second chance at life that I have been given.

To request a swab kit and register as a potential donor click HERE.

About blood cancer

Blood cancer is the third most common cause of cancer death in the UK but there is a lot of fear around stem cell donation of the process itself and of having a depleted supply of stem cells. This isnt the case. After donation, stem cells regenerate within 2 weeks so the donor wont lose anything. Blood stem cell donation is easy to do and similar to blood donation. Around 90% of all donations are made through a method called peripheral blood stem cell (PBSC). In this method, blood is taken from one of the donors arms and a machine extracts the blood stem cells from it. The donors blood is then returned to them through their other arm. This is an outpatient procedure that is usually completed in 4-6 hours. In just 10% of cases, donations are made through bone marrow collection. This is under general anaesthetic so that no pain is experienced.

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Black History Month The struggle to find a lifesaving stem cell donor - Keep the Faith

Novellus Therapeutics Exclusively Licenses Induced Mesenchymal Stem Cells (iMSCs) to NoveCite

"Novellus's iMSCs have the potential to be a breakthrough in the field of cellular therapy for acute respiratory conditions because of their high potency as demonstrated in our pre-clinical studies, as well as our ability to cost-effectively provide high doses and repeat doses." said Myron Holubiak, CEO of Citius.

"We are excited to be developing iMSCs because of their promise to save lives and reduce long term sequelae in patients with devastating respiratory diseases such as ARDS caused by COVID-19," said Matt Angel, Chief Science Officer of Novellus. He continued, "Our iMSCs have multimodal immunomodulatory mechanisms of action that make them promising for treatment of acute respiratory diseases."

About Novellus Therapeutics LimitedNovellus is a pre-clinical stage biotechnology company developing engineered cellular medicines using its patented non-immunogenic mRNA, high-specificity gene editing, mutation-free & footprint-free cell reprogramming and serum-insensitive mRNA lipid delivery technologies. Novellus is privately held and is headquartered in Cambridge, MA. For more information, please visit http://www.novellustx.com.

About NoveCite, Inc.NoveCite, Inc. is a newly formed subsidiary of Citius Pharmaceuticals, a late-stage specialty pharmaceutical company dedicated to the development and commercialization of critical care products, with a focus on anti-infectives and cancer care. For more information, please visit http://www.citiuspharma.com.

Contact: [emailprotected]

SOURCE Novellus Therapeutics

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Novellus Therapeutics Exclusively Licenses Induced Mesenchymal Stem Cells (iMSCs) to NoveCite for COVID-19 Related Acute Respiratory Distress Syndrome...

Dr. Odalis Mara de la Guardia Pea, a second degree specialist in Immunology, has defined as promising the preliminary results obtained at the end of the first phase of the clinical trial for the use of mother cells in patients who have suffered lung lesions due to COVID-19.

The study began in March this year at the Institute of Hematology and Immunology (IHI) and aims to eliminate or soothe inflammatory interstitial or fibrotic lesions resulting from COVID-19 disease, which often force surviving patients to long periods of pulmonary rehabilitation.

If the study using stem cells will be successful, say Dr. Odalis Mara de la Guardia Pea and the other authors, it will be possible to generalize the treatment and extend it to patients of other diseases with equal legacy on the patients body.

The target organs of the coronavirus are different: it affects, is a verified scientific fact, heart, kidney, brain, vascular system, and nervous system (especially the peripheral of the lower limbs).

But it is the lung that seems to feel the effects of the infection.

At least in terms of frequency, if not gravity.

A study that was carried out directly in the patients homes: 130 homes were visited in about three months, from May to June; 141 patients were interviewed and 50 among them were studied.

In the essay were added 20 patients, the amount determined.

During the investigation, several consequences of COVID-19 were appreciated, although the most frequent was lung damage.

In some cases the appearance of signs of pulmonary fibrosis was noted, a problem that cannot be fully corrected and that can only be treated to increase lung capacity and improve the quality of life, explained the head of External Services of the IHI.

The study is in the process of being finalized. The first part is finished, but it takes some time to make the final assessment of the patient.

What we can say is that so far we are very happy with the results we have observed, which are promising, said the doctor.

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Our respiratory system: a virtual tour inside our body

Gramma

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Cuba, study on the effects of COVID-19 in the lungs: use stem cells - Emergency-Live

IRVINE, Calif., Oct. 9, 2020 /PRNewswire/ --AIVITA Biomedical Inc., a private biotechnology company developing personalized vaccines for the treatment of cancer and COVID-19, announced today the publication of the peer-reviewed manuscript, "Retina organoid transplants develop photoreceptors and improve visual function in RCS rats with RPE dysfunction,"in the journal Investigative Ophthalmology & Visual Science. The study, led by researchers at AIVITA Biomedical and the Sue & Bill Gross Stem Cell Research Center of the University of California, Irvine, used 3D-retina organoids generated from human stem cells developed by AIVITA to provide insight into the potential use of transplanted retina organoids as a therapeutic option for blinding diseases.

In the study, transplanted retina organoid sheets were examined to determine if human stem cell-derived photoreceptors coulddevelop, survive and function in vivo without the support of healthy retina pigment epithelium (RPE). Visual function was examined through a variety of tests, including optokinetic testing (OKT), electroretinogram (ERG), and superior colliculus (SC) brain recording. These tests concluded that retina organoid transplantations demonstrated significant improvement in visual function compared to non-surgery and sham surgery controls, supporting the application of AIVITA's stem cell technologies in visual disease therapeutics.

"Leveraging our expertise in stem cell growth and differentiation, I'm excited to see the promise of our technology platform in potential therapeutics for vision loss," said Hans Keirstead, Ph.D., chief executive officer of AIVITA and a contributing author to the paper. "To our knowledge, this study is the first to show that it's possible for photoreceptors derived from stem cells to survive and function after transplantation when a host has a dysfunctional RPE."

This work is supported by funding from the California Institute for Regenerative Medicine (CIRM) and National Institutes of Health (NIH).

About AIVITA Biomedical AIVITA Biomedical is a privately held company engaged in the advancement of commercial and clinical-stage programs utilizing curative and regenerative medicines. Founded in 2016 by pioneers in the stem cell industry, AIVITA Biomedical utilizes its expertise in stem cell growth and directed, high-purity differentiation to enable safe, efficient and economical manufacturing systems which support its therapeutic pipeline and commercial line of skin care products. All proceeds from the sale of AIVITA's skin care products support the treatment of people with cancer.

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SOURCE AIVITA Biomedical, Inc.

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AIVITA Biomedical's Stem Cell Therapeutic in Vision Loss Published in Investigative Ophthalmology & Vision Science - BioSpace

A company born at the University of Louisville has raised an additional $115 million to further develop a therapy that could improve the lives of kidney transplant recipients.

The company, Talaris Therapeutics Inc., plans to use the series B funding to support a Phase 3 clinical trial the last step before applying for FDA approval. This follows a $100 million series A funding round announced last year to hire staff and initiate the trial.

Talaris recently began dosing patients in that trial of the unique cell therapy, called FCR001, which allows living-donor kidney transplant recipients to stay off immunosuppression drugs they would otherwise need for the rest of their lives.

Immunosuppressants help prevent rejection of the transplanted organ, but can cause side effects, including high blood pressure, diabetes, high cholesterol, neurological effects, increased risk of infection and decline in kidney function over time.

This technology could help transplant patients live fuller, healthier lives,said UofL Executive Vice President for Research and Innovation, Kevin Gardner.This UofL research, in the hands of strong industry partners and backed by investors, is a big step in advancing our health.

FCR001 consists of stem cells taken from the organ donor and processed at the Talaris facility, then infused into the organ transplant recipient. The goal is to create a durable dual immune system (part donor-derived and part recipient) in the transplant recipient. These two immune systems coexist, recognizing both the recipients own body as well as the donated organ as self.

The new funding also will advance aplanned Phase 2 trial of FCR001 in diffuse systemic sclerosis, a severe form of the rare autoimmune disease scleroderma.

Talaris, formerly known as Regenerex LLC, was founded by UofL researcher and innovator Suzanne Ildstad to commercialize the pioneering work of her team at the university. She now serves as Talaris chief scientific officer.

This financing moves us one step closer to helping organ transplant recipients no longer be dependent on immunosuppressive drugs, resulting in a greatly improved quality of life, Ildstad said of the earlier Phase 3 trial financing. The support and research infrastructure at UofL have been invaluable in our journey to this important juncture.

In an earlier Phase 2 trial, FCR001 allowed 70% of living donor kidney transplant patients durably to be weaned off all of their immunosuppression treatments.

The Phase 3 trial is expected to enroll 120 adult living donor kidney transplant recipients at multiple sites across the U.S. To date, the trial has been initiated at five clinical sites around the country.

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UofL-born company secures an additional $115 million to advance cell therapy - uoflnews.com

This article was originally published here

Life Sci. 2020 Oct 10:118588. doi: 10.1016/j.lfs.2020.118588. Online ahead of print.

ABSTRACT

The severe acute respiratory syndrome-novel coronavirus mediated COVID-19 has been recently declared a pandemic by the World Health Organization. The primary target of the SARS-CoV-2 virus is the human lungs governed by the ACE-2 receptor of epithelial type II cells/endothelial cells, which promote modulation of the immune response of host cells through generating cytokine storm, inflammation, severe pneumonia symptoms, and secondary complications such as acute respiratory distress syndrome. Although numerous antiviral and anti-parasitic drugs are under clinical trials to combat this pandemic, to date, neither a specific treatment nor any successful vaccine has been established, urging researchers to identify any potential candidate for combating the disease. Mesenchymal stem cells own self-renewal, differentiation, homing, immunomodulation and remains unaffected by the coronavirus on the virtue of the absence of ACE-2 receptors, indicating that MSCs could be used an ameliorative approach for COVID-19. MSCs have shown to combat the disease via various pathways such as repairing the lung epithelial and endothelial cells, reducing hyperimmune response, maintaining the renin-angiotensin system. Although MSCs-based treatment approaches for COVID-19 is still under consideration with limited data, many human clinical trials of MSCs has been initiated to explore their potential for COVID 19 treatment. The current review summarizes and emphasizes on how MSCs modulate the immune response, can repair the lungs from the impact of the virus, and various aspects of MSCs as a remedial source for COVID-19, to provide better insight for biomedical researchers and for those who are fascinated by stem cells as a therapeutic approach.

PMID:33049279 | DOI:10.1016/j.lfs.2020.118588

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Mesenchymal stem cell immunomodulation and regeneration therapeutics as an ameliorative approach for COVID-19 pandemics - DocWire News

Rosh Hashanah is the day of pregnancy of the world. Hayom Harat Olam (The day of creation of the world). What does it mean?Medical research today is focusing on a fascinating and visionary field, which is the study of "stem cells."The uniqueness of stem cells comes from two main features which distinguish them from other cells. The first is that they are still 'neutral cells', meaning, they have not yet received their final identity and purpose in the body, so they have not yet finalized their differentiation process. As a result of this, they are able to differentiate and can develop into one of many types of mature cells, such as a skin cell, a muscle cell or a blood cell. By doing so, new cells are created, which can regenerate various tissues and organs.The second unique feature of stem cells is that they are able to divide and multiply infinitely and produce identical cells. Thus, a constant pool of unsorted stem cells that have not acquired a final designation is preserved.The possibilities of healing, cell regeneration and the human body in general are fascinating, and the field of stem cells is one of the leading fields in the world. Its healing potentials are so vast, not only when it comes to repairing the damaged, but also recreating something more true and precise.When I think of Rosh Hashanah from a spiritual standpoint, it feels like today is the birth of the world. We have before us 353 days (because some Jewish months arent full) which have not yet been defined by how they will play out and how they will look. It is unknown how we will succeed as individuals, and how we will succeed as nation. Interestingly, the second feature that exists with stem cells also connects to Rosh Hashanah. On this holy day, we are praying and asking Hashem from a place of "anything is possible" there are no boundaries, no glass barriers, no one is stopping us from simply praying and asking. cnxps.cmd.push(function () { cnxps({ playerId: '36af7c51-0caf-4741-9824-2c941fc6c17b' }).render('4c4d856e0e6f4e3d808bbc1715e132f6'); });Hashem, everything is completely in our hands! We can change the world and create something entirely new. Rosh Hashanah gives us the opportunity to create and build anew; its the source of rebirth for the relationship between man and his friend, man and Hashem, and of course, man as one who is part of a nation and of the entire world.It's not for nothing that it is written in the Talmud Yerushalmi that whoever spends his time on Rosh Hashanah sleeping, his luck will also sleep. It's the time to act, ask, beg and change.The cells will divide, the decisions made will be in place, and the abundance from shamayim (heaven) will come down. We now have a very great ability and opportunity to influence that. Please dont miss out on this opportunity!Be that as it may, today is Harat Olam the pregnancy of the world. It is our responsibility to pray that this pregnancy will be the best it can be. Have a happy and sweet New Year.Rabbi Yitzak Neriya is the head of the Torah Betzion yeshiva and founder of the Echad Lechad (One to One) foundation.

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Stem cells, like Rosh Hashanah, give the opportunity to be reborn - The Jerusalem Post

SIOUX FALLS, S.D. Sanford Health is launching a first-of-its-kind study that uses umbilical stem cells to treat people sick with COVID-19.

The Sioux Falls-based health system has enrolled five patients at Sanford USD Medical Center in Sioux Falls in the trial, which uses umbilical cord lining stem cells to treat patients with moderate to severe COVID-19 both before and every they've been placed on a ventilator, it announced Tuesday, Sept. 8. It may expand the study to patients in Fargo.

We are optimistic about the potential improvement with this treatment, Dr. W. Chad Spanos, principal investigator of the clinical trial at Sanford Health, said in a news release. We look forward to enrolling more patients onto this trial and bringing promising new treatment options to our patients bedside in the future.

The randomized, placebo-controlled and blinded phase 1/2a study will look at whether infusing patients with the stem cells could be a safe and effective treatment for COVID-19. The trial also aims to identify the population that will benefit most optimally by enrolling patients with moderate to severe COVID-19.

Sanford Health is the largest rural nonprofit health care system in the nation with clinics across the Upper Midwest and major medical centers in Sioux Falls, Fargo and Bemidji, Minn.

Were committed to bringing the best treatments and discoveries to our patients first, David A. Pearce, president of innovation and research at Sanford Health, said in a news release. We are thrilled to be the first health system in the country to open this trial and offer access to a novel treatment option to our patients with severe cases of COVID-19.

The study will use cells provided by RESTEM, a biotechnology firm which uses a proprietary process to rapidly replicate millions of doses from umbilical cord tissue.

Its a pleasure to work with Sanford Health and their team of professionals, said Dr. Rafael Gonzalez, senior vice president of research & development for RESTEM. We have spent many years researching the properties of (umbilical cord lining stem cells) in order to assure we are delivering the best quality cells that may provide a robust response. We look forward to the results of the study.

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Sanford Health launches first-of-its-kind study of umbilical stem cells as COVID-19 treatment - The Daily Republic