Stem cell research uncovers clues to tissue repair that could help heal the uterus and more

Stem cells play a vital role in repairing damaged tissue, whether it’s 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 don’t fully understand how the cells are able to help damaged areas regenerate.

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 O’Keeffe Young Professor of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine and the study’s principal investigator.

Stem cells secrete miRNAs that support cell proliferation

Exosomes are extracellular vesicles, which contain various bioactive molecules and allow cells to communicate with one another. In their new study, Taylor’s 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. It’s 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.”

Turning miRNAs into drugs for tissue repair

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, Taylor’s 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 that’s injury due to trauma or degenerative diseases,” says Taylor.

This research was funded by the National Institutes of Health.