Bone marrow mesenchymal stem cells reduce ureteral stricture formation in a rat model via the paracrine effect of extracellular vesicles

Abstract

With no effective therapy to prevent or treat ureteral stricture (US), a multifactorial fibrotic disease after iatrogenic injury of the ureter, the need for new therapies is urgent. Mesenchymal stem cells (MSCs) have been widely studied for treating tissue defects and excessive fibrosis, and recent studies established that one of the main therapeutic vectors of MSCs is comprised in their secretome and represented by extracellular vesicles (EVs). Thus, we have determined to explore the specific role of MSCs‐derived EVs (MSC‐EVs) treatment in a pre‐clinical model of US. The results firstly showed that either a bolus dose of MSCs or a bolus dose of MSC‐EVs (administration via renal‐arterial) significantly ameliorated ureteral fibrosis and recuperated ureter morphological development in a US rat model. We confirmed our observations through MSCs or MSC‐EVs treatment alleviated hydronephrosis, less renal dysfunction and blunted transforming growth factor‐β1 induced fibration. Due to MSC‐EVs are the equivalent dose of MSCs, and similar curative effects of transplantation of MSCs and MSC‐EVs were observed, we speculated the curative effect of MSCs in treating US might on account of the release of EVs through paracrine mechanisms. Our study demonstrated an innovative strategy to counteract ureteral stricture formation in a rat model of US.

Anti-inflammatory protein TSG-6 secreted by bone marrow mesenchymal stem cells attenuates neuropathic pain by inhibiting the TLR2/MyD88/NF-κB signaling pathway in spinal microglia

“…Initially, studies tested the homing characteristic of BMSCs to the injury site and the potential of BMSCs to repair damaged tissues by differentiating into the appropriate cell type. Recently, an increasing number of studies have demonstrated that the protective effects of BMSCs might be due to their potent immunomodulatory and immunosuppressive properties via paracrine secretions [55,56]. In the present study, we also found that BMSCs inhibited the expression of pro-inflammatory cytokines and the activation of microglia in the spinal cord dorsal horn by secreting soluble factors.…”

Reproducibility of GMP-compliant production of therapeutic stressed peripheral blood mononuclear cell-derived secretomes, a novel class of biological medicinal products

“…Thus far, no consensus culture protocol is available for promoting the most effective release of regenerative factors, and no agreement yet exists on the most potent source for secretory cells. In contrast to our irradiation, the vast majority of studies employ secretomes from cultured cells without additional stimulation or challenge [10, 12, 13]. However, a limited number of reports have already demonstrated superior effects when manipulating SCs in vitro to promote increased release of regenerative factors.…”

“…However, the initial idea of transdifferentiating SCs for tissue repair [6] was refuted by more recent studies, which reported that SC integration into damaged tissues is poor [7] and that SC-derived paracrine factors rather than transplanted SCs themselves are responsible for functional restoration of injured tissues and organs [8, 9]. The efficacy of SC-derived secreted factors was later demonstrated in various pre-clinical studies [10–13], and the use of cell-free therapeutic agents is encouraged in numerous indications (reviewed in [14–19]). Using cell-free paracrine factors exhibit several advantages compared to cell-based therapeutics and resolve major safety considerations of cell transplantation.…”

Mesenchymal stem cell‐derived exosomes ameliorate erection by reducing oxidative stress damage of corpus cavernosum in a rat model of artery injury

“…11 Exosome of MSC is an important bioactive substance vector which contains multiple types of nucleic acids, lipids and proteins. 12 They have been demonstrated to involved in multiple pathologic and physiologic processes, which include proliferation and differentiation, 24 anti-fibrosis, 25 immunomodulation 26 and tissue regeneration. 27 In our study, exosomes were isolated from the culture supernatants of MSCs, and these pellets proved could ameliorate rat's erectile function independently with similar potency compared with the MSCs group.…”