Stem Cell Clinic

Stem Cell Research Uncovers Clues to Tissue Repair That Could Help Heal the Uterus and More – Yale School of Medicine

Stem cells play a vital role in repairing damaged tissue, whether its a scraped knee or a scarred uterus following pregnancy. New stem cell research has identified the molecules that the cells produce to promote the healing process. The finding could pave the way for the development of new, more effective drugs for injuries or various diseases, including conditions related to reproductive health such as Asherman syndrome, a gynecologic condition in which the uterus scars and becomes fibrotic.

Scientists believed in the past that stem cells served as backup cells that repaired tissues by differentiating into new cells that repopulated the site of injury. Now, they have learned that it is rare for stem cells to completely replace injured tissue. But they still dont fully understand how the cells are able to help damaged areas regenerate.

We found the molecules that stem cells make to help heal and repair tissue, and we hope that understanding this will be potentially useful as a medication in the future.

In the uterus, stem cells play a number of roles, including helping it to expand during pregnancy and to regenerate and repair after childbirth. This new study identified several microRNAs (miRNAs) secreted by the stem cells that helped drive the growth and proliferation of cells in uterine tissue. The researchers published their findings in Stem Cell Research & Therapy on May 1.

We found the molecules that stem cells make to help heal and repair tissue, and we hope that understanding this will be potentially useful as a medication in the future, says Hugh Taylor, MD, chair and Anita OKeeffe Young Professor of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine and the studys principal investigator.

Exosomes are extracellular vesicles, which contain various bioactive molecules and allow cells to communicate with one another. In their new study, Taylors team isolated exosomes secreted by stem cells from human bone marrow. They then used RNA sequencing to characterize all of the miRNA contained in the vesicles and identified those that were most abundant. Then researchers took the most prominent miRNAs and introduced them into human uterine tissue.

The team found that the miRNAs significantly increased the growth and proliferation of the uterine cells. They also studied their effect on the cells decidualization in the endometrium. (Decidualization is the differentiation process uterine cells undergo that prepares the uterus to support an embryo.) The study showed that the miRNAs blocked decidualization.

In a uterus, once a cell becomes differentiated to support pregnancy, it can no longer repair and regenerate. Its permanently locked in that state and often is shed through menstruation later on, says Taylor. By blocking this process, it allows the cells to focus on proliferating and turns on these reparative processes.

The study offers insight into how stem cells promote reparative processes without replacing the tissue itself. Taylor hopes that as researchers continue to gain a greater understanding about how miRNAs work, they could one day be used as drugs for repairing various damaged tissue.

Asherman syndrome, for example, typically occurs after pregnancy, when the supply of stem cells may not be adequate to help the organ heal properly, which can hinder fertility in the future. The idea is that these miRNAs could be used as a medication that is much more readily available and practical, says Taylor. We could potentially deliver them to help prepare the uterus in the critical window when it is damaged and may be vulnerable.

The finding could also have significance beyond the uterus. In future stem cell research, Taylors team plans to study how miRNAs respond to other types of traumatic tissue injury in animal models. We studied the uterus, but the implications are beyond reproduction, potentially including many other conditions where stem cells are involved in repair and regeneration, whether thats injury due to trauma or degenerative diseases, says Taylor.

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Stem Cell Research Uncovers Clues to Tissue Repair That Could Help Heal the Uterus and More - Yale School of Medicine

Cancer Patients Who Need Stem Cell Transplants May Have New Donor Options – Everyday Health

For some people with blood cancers who need a stem cell transplant, finding a donor who is an excellent match can mean the difference between life and death.

Unfortunately, even though there are more than 40 million potential donors in the national registry, finding a perfect match isnt always possible, especially in underrepresented racial and ethnic groups.

But a new approach using an old chemotherapy drug,cyclophosphamide, isis opening up new possibilities for people with cancers like leukemia, lymphoma, and multiple myeloma. Researchers have found that by administering the drug several days after transplantation, people receiving blood stem cells from unrelated, partially matched donors can have survival rates comparable with those who received exactly matched cells.

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This innovative approach can greatly expand patient access to safe and effective stem cell transplant, regardless of matching degree with the donor, says lead coauthor Monzr M. Al Malki, MD, a hematologist and oncologist and director of the Unrelated Donor BMT program at City of Hope, a cancer research and treatment organization with locations across the United States.

Thats exciting because it means more patients will be able to receive this potentially life-extending therapy, says Dr. Al Malki.

Donor compatibility is determined by a set of protein markers on blood cells called HLAs (human leukocyte antigens), says David Miklos, MD, a professor of medicine and chief of Stanford BMT and Cell Therapy Program at Stanford Medicine in California. Stanford was one of the medical sites of the trial, though Dr. Miklos is not a coauthor of the research.

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Why was an exact match needed? Anything less increased the likelihood of a graft failure, as well as graft-versus-host disease meaning the transplanted cells attack the patients own, which can cause serious or even fatal complications, explains Miklos.

About a decade ago, researchers started using cyclophosphamide to destroy the parts of a persons immune system that would reject the transplant. That breakthrough allowed researchers to not only have better outcomes in fully matched donors, it also opened the door for successful transplants between people who were only partial matches.

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The new study looked at cyclophosphamide treatment in patients receiving peripheral blood stem cell transplantation meaning healthy stem cells are harvested from a donors bloodstream, and then administered via infusion to the person with cancer.

Blood stem cell transplantation has largely replaced bone marrow transplantation, according to researchers.It's an easier way of collecting stem cells from donors, and its a little safer, because donors dont need to be under anesthesia as they would in bone marrow transplantation, says Al Malki.

For this part of the study, the researchers examined data from 70 adults who were 65 years old on average, all with advanced blood cancers. Participants received a reduced-intensity conditioning regimen to somewhat suppress their immune system to prepare them for transplantation, followed by an infusion stem cells from unrelated, partially matched donors.

The researchers reported an overall high survival rate of 79 percent at one year which is comparable to survival rates seen with fully matched donors.

The main side effect or risk of transplantation is graft-versus-host disease, says Al Malki. After one year, 51 percent of participants were free of the disease and had not relapsed, which is also comparable to what would be seen with fully matched donors, he says.

Historically, barriers in access to transplant have existed due to the low availability of matched, related sibling donors, as well as the substantial variance of matched, unrelated donor availability, especially for patients with diverse ancestry, says study coauthor Steven M. Devine, MD, chief medical officer of NMDP (formerly known as the National Marrow Donor Program and Be The Match).

These findings advance our ability to offer more options to patients without a fully matched donor, many of whom are ethnically diverse and have been underserved in receiving potentially lifesaving cell therapy, says Dr. Devine.

These findings are incredibly important and critical in the effort to improve existing inequities, says Miklos.

In the past, we could not bring some patients forward to receive this lifesaving therapy because they didnt have a compatible donor, but with the new approach of using post-transplant cyclophosphamide, all patients have donors now, he says.

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Cancer Patients Who Need Stem Cell Transplants May Have New Donor Options - Everyday Health