Title : Understanding the mesenchymal stem cells role in uterine and intestinal tissue regeneration
Abstract:
Introduction: Among the other tissue-resident adult stem cells, Mesenchymal stem cells (MSCs) are well characterized by their immune-modulatory and regenerative functionality (1). Impairment of tissue regeneration leads to fibrosis/ scar formation (2). To understand the mechanism of scar-free tissue repair by resident adult stem and immune cells, we selected intestine and endometrium tissues. These are the extremely regenerative organs in the human body. The intestine redevelops its lining, epithelium, every 3-4 days (3). The endometrium (the inner lining of the uterus) suffers monthly shedding and regeneration, pivotal for successful reproduction (4). We aim to identify the role of tissue- resident MSCs in the regulation of intestinal and endometrial homeostasis.
Methods: We created colitis-mediated intestinal damage in mice and exogenously delivered MSCs to these colitis mice. We studied the immune phenotype of intestinal macrophage/ B or T cells. To characterize intestinal MSCs, we collected MSCs from mice intestines with a standard collagen digestion method and characterized them based on MSCs-specific markers. We measured R-spondin- 3/Wnt5a expression, the two morphogens with known function in epithelial stem cell biology. We also measured Collagen 1 and 5 expression, components of fibrosis.
To identify the role of MSCs in endometrium regeneration, MSCs, and stromal cells were collected from the menstrual blood of healthy women. Endometrial stromal cells were treated with MSCs- condition media. Stromal cell proliferation, random and collective migration were assayed using standard biochemical assays. MSC-CM-treated stromal cells ability to reform the endometrial tissue was measured by tissue decellularization/ recellularization technique.
Conclusion: MSCs derived secretome (MSC-CM) reduces tissue inflammation and induces tissue regeneration in the intestine and endometrium.
Significance: MSC-CM can be a novel cell-free therapy against uterine/endometrium damage.
