Administration of secretome from human placental stem cell‐conditioned media improves recovery of erectile function in the pelvic neurovascular injury model

Abstract

Human placental stem cells (PSCs) enhance histological and functional recovery in a rodent erectile dysfunction (ED) model. We tested the hypothesis that bioactive factors secreted by PSC (i.e., the secretome) mediate functional recovery and that acellular-conditioned media (CM) from PSC culture (PSC-CM) could be used independently to facilitate functional and histological recovery. To identify factors relative to efficacy of PSC, a comparison of CM from PSC and three additional human stem cell populations was performed. CM from human PSC, amniotic fluid stem cells (AFSCs), adipose-derived stem cells (ADSC), and human umbilical vein endothelial cells (HUVECs) was assayed using a semi-quantitative human cytokine antibody array. Male rats, after surgically created ED by neurovascular injury, were randomly divided into four groups: vehicle control (phosphate-buffered saline [PBS]), PSC, PSC-CM, and serum-free media control (SFM) as control. Functional data on intracorporal and mean arterial pressure were obtained, and histological architecture was examined 6 weeks after single injection. PSCs were found to secrete at least 27 cytokines and growth factors at a significantly higher level than the other three cell types. Either single injection of PSC-CM or PSC significantly improved erectile functional recovery and histological architecture compared with SFM or PBS. Injection of the secretome isolated from human PSC improves erectile functional recovery and histological structure in a rat model of neurovascular injury-induced ED. Further characterization of the unique protein expression within the PSC-CM may help to identify the potential for a novel injectable cell-free therapeutic for applicable patients.

Human placental-derived stem cell therapy ameliorates experimental necrotizing enterocolitis and supports restoration of the intestinal stem cell niche

“…The hPSC secretome possesses factors that can potentially support epithelial restitution and repair (41,55). Therefore, we also examined the epithelial damage in NEC by first assessing the crypt/villus architecture in the ileum.…”

“…Perinatal stem cells present a unique approach known for broader immune modulation rather than specific inflammatory suppression (36,62). hPSC also uniquely secrete a multitude of factors that can target other components of NEC pathogenesis via potent paracrine signaling (27,37,41). Therefore, we hypothesized that hPSC therapy was a novel multi-faceted paracrine approach that could improve epithelial damage and reduce pathogenic inflammation in NEC disease.…”

“…From the whole placental tissue, the chorion was biopsied and then digested to isolate perinatal placental cells as previously described (11,41). Briefly, isolated placental cells were plated in α-MEM supplemented with AmnioMax and Glutamax.…”

“…hPSC possess similar proliferative and multipotency characteristics to other perinatal stem cells, however, they also express a unique secretome (41). hPSC have been shown to have immunomodulatory factors and capabilities (40), and also express several factors that can directly promote intestinal epithelial healing and regeneration, including ICAM1, NRG1, EGFR, and Lactoferrin (41). Together, these data suggest that hPSC may be a potential multifaceted therapy to combat NEC pathogenesis.…”

“…However, the placenta, long considered medical waste that can simply be collected after healthy birth, is now being regarded as a more optimal tissue for perinatal stem cell isolation. hPSC possess similar proliferative and multipotency characteristics to other perinatal stem cells, however, they also express a unique secretome (41). hPSC have been shown to have immunomodulatory factors and capabilities (40), and also express several factors that can directly promote intestinal epithelial healing and regeneration, including ICAM1, NRG1, EGFR, and Lactoferrin (41).…”