towards stem cell therapy of polycystic ovary syndrome (PCOS): therapeutic effect of human mesenchymal stem cells transplantation in pcos mouse model by regulating ovarian vascularization

• Published in: Cytotherapy (Oxford, England) England), 2019-05, Vol.21 (5), p.S78-S78
• Main Authors: Park, H, Ashour, D, Elsharoud, A, Chugh, R, Al-Hendy, A, El Andaloussi, A
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Other
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2019.03.484

Background & Aim BackgroundWomen with the polycystic ovarian syndrome (PCOS) have an increase in ovarian androgen production. Recent studies report that angiogenesis is aberrantly increased in ovaries of PCOS patients. Angiogenesis play an important role in inflammatory response as well as it might be promoted by inflammation as well. We have recently reported that intra-ovarian implanted human mesenchymal stem cells (hMSCs) can decrease serum androgen levels in a PCOS animal model. However, it is still unknown how hMSCs exert its effect on PCOS ovary. The hMSCs are well known regulator of inflammatory response and angiogenesis. These abilities of hMSCs could be strong candidate to explain the mechanism of how they reverse the phenotype of PCOS.HypothesisWe hypothesis that hMSCs can reverse PCOS ovary into normal phenotype by regulating inflammatory response and blood vessel formation.Methods, Results & Conclusion Material and MethodIn this study, we induced PCOS in C57/BL6 mice by daily Letrozole from week 4 to week 9 of age. We then engrafted hMSCs (500,000 cells/ovary) by direct intra-ovarian injection. 2 weeks later, we sacrificed the mice and collected the ovaries to analyze the inflammatory markers IL-6, IL-1α, the angiogenesis markers VEGFA, ANGPT1, and the blood vessels markers αSMA, vWF by PCR, immunohistochemistry and western blot examination.ResultImplantation of hMSCs significantly suppressed the levels of IL-6 and IL-1α (P< 0.05) in the ovarian tissue compared to sham/vehicle control mice. We also observed that hMSCs treatment decreased the expression of alpha smooth muscle actin (P< 0.05) in the PCOS ovaries compared to sham/vehicle control mice.ConclusionOur data reveal that ovary of letrozole induced PCOS mouse showed increased inflammation and angiogenesis compared to healthy controls. This alteration can be reversed by intra-ovarian hMSCs transplantation. Our study showed that hMSCs injection in PCOS ovaries can normalize inflammatory status and angiogenesis and may present a novel treatment modality for PCOS patients.