Human Adipose-derived Pericytes Display Steroidogenic Lineage Potential in Vitro and Influence Leydig Cell Regeneration in Vivo in Rats.

Exogenous androgen replacement is used to treat symptoms associated with low testosterone in males. However, adverse cardiovascular risk and negative fertility impacts impel development of alternative approaches to restore/maintain Leydig cell (LC) androgen production. Stem Leydig cell (SLC) transplantation shows promise in this regard however, practicality of SLC isolation/transplantation impede clinical translation. Multipotent human adipose-derived perivascular stem cells (hAd-PSCs) represent an attractive extragonadal stem cell source for regenerative therapies in the testis but their therapeutic potential in this context is unexplored. We asked whether hAd-PSCs could be converted into Leydig-like cells and determined their capacity to promote regeneration in LC-ablated rat testes. Exposure of hAd-PSCs to differentiation-inducing factors in vitro upregulated steroidogenic genes but did not fully induce LC differentiation. In vivo, no difference in LC-regeneration was noted between Sham and hAd-PSC-transplanted rats. Interestingly, Cyp17a1 expression increased in hAd-PSC-transplanted testes compared to intact vehicle controls and the luteinising hormone/testosterone ratio returned to Vehicle control levels which was not the case in EDS + Sham animals. Notably, hAd-PSCs were undetectable one-month after transplantation suggesting this effect is likely mediated via paracrine mechanisms during the initial stages of regeneration; either directly by interacting with regenerating LCs, or through indirect interactions with trophic macrophages.

Skeletal and cardiac muscle pericytes: Functions and therapeutic potential.

Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease.