Acceleration of pelvic tissue generation by overexpression of basic fibroblast growth factor in stem cells

Abstract

ABSTRACT Background Pelvic organ prolapse (POP) is a common debilitating condition affecting approximately 30–40% of women. The FDA issued a warning about polypropylene mesh used for pelvic floor repair due to erosion, exposure and other complications and banned it in 2019. The application of stem cell therapy and growth factors has strongly promoted the development of pelvic tissue engineering. Purpose we intend to address the issues of direct application of growth factors, the side effects of long-term exogenous treatment, and the directional differentiation of stem cells. Methods: we evaluated the paracrine effects and directional differentiation of adipose mesenchymal stem cells through stable overexpression of basic fibroblast growth factor (bFGF). Results we found that the modified stem cells could continuously and stably release bFGF in the initial stage and could spontaneously differentiate into fibroblasts with a high differentiation efficiency in the later stage. Conclusion following ADSCs are designed to continuously release controllable levels of growth factors during the control period of repair, taking advantage of the paracrine function of stem cells to accelerate cell growth and extracellular matrix (ECM) reconstruction during the early stage of stem cell implantation, and then stem cells are differentiated into target tissues-fibroblasts to accelerate the reconstruction of pelvic floor tissues, this study demonstrated the strong therapeutic potential of this approach for pelvic tissue engineering. Abbreviations POP: Pelvic organ prolapse; ADSCs: Adipose-derived stem cells; bFGF: Basic fibroblast growth factor; BMSCs: Bone marrow-derived mesenchymal stem cells; HUVECs: Human umbilical vein endothelial cells; EMSCs: Endometrial mesenchymal stem cells; VEGF: Vascular endothelial growth factor; PDGF: Platelet-derived growth factor ECM: Extracellular matrix; IGF: Insulin-like growth factor; HGF: Hepatocyte growth factor; EGF: Epidermal growth factor; BMP-2: Bone morphogenetic protein 2; FBR: Foreign body reaction.