Secretomes from human pluripotent stem cells-derived smooth cell progenitors regulate extracellular matrix metabolism of the lower urinary system and vaginal & Therapy
Around 2021, secretomes from human pluripotent-stem cell-derived smooth muscles cell progenitors regulate extracellular matrix metabolism both in the lower urinary system and vagina.
MSCs (adult mesenchymal cells) are extensively studied for regenerative medicine. However, their limited proliferation in vitro and the prolonged culture time causes cell senescence. MSCs contribute to tissue repair via their paracrine functions. In this study, our goal was to investigate the paracrine effect of human smooth cell progenitors on the urethra of rodents with stress urinary incontinence. To overcome the problem of reduced proliferation in tissue cultures and obtain homogeneous cells, we use human pluripotent (PSC-) lines to derive our pSMCs.
Three human PSCs were differentiated to pSMCs. The conditioned media (CM) containing pSMCs secretomes was obtained from pSMC cultures. In vitro, human bladder smooth muscles cells (bSMCs), and vaginal fibroblasts treated with pSMC CM were used to examine the effects of the CM. In order to induce stress urinary incontinence in rats, surgical injury was performed on the urethra or adjacent vagina. SUI rats treated with pSMCCM were monitored for five weeks. Prior to euthanasia tissues were collected for PCR, Western blot and histological staining. For statistical comparisons, the Kruskal Wallis one-way ANOVA and Student t tests were used.
pSMC CM increased MMP-2 and TIMP-2 gene expression and MMP-9 in human bladder and vaginal cell, consistent with modulation of elastin metabolism. pSMC treatment of the SUI rat increased urethral (leak point) pressure and collagen and elastin in the urethra, and adjacent vagina.
Source:
https://stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02292-y
