Amniotic fluid stem cell exosomes: Therapeutic perspective

Abstract

It is widely accepted that the therapeutic potential of stem cells can be largely mediated by paracrine factors, also included into exosomes. Thus, stem cell-derived exosomes represent a major therapeutic option in regenerative medicine avoiding, if compared to stem cells graft, abnormal differentiation and tumor formation. Exosomes derived from mesenchymal stem cells (MSC) induce damaged tissue repair, and can also exert immunomodulatory effects on the differentiation, activation and function of different lymphocytes. Therefore, MSC exosomes can be considered as a potential treatment for inflammatory diseases and also an ideal candidate for allogeneic therapy due to their low immunogenicity. Amniotic fluid stem cells (AFSCs) are broadly multipotent, can be expanded in culture, and can be easily cryopreserved in cellular banks. In this study, morphology, phenotype, and protein content of exosomes released into amniotic fluid in vivo and from AFSC during in vitro culture (conditioned medium) were examined. We found that AFSC-derived exosomes present different molecules than amniotic fluid ones, some of them involved in immunomodulation, such transforming growth factor beta and hepatic growth factors. The immunomodulatory effect of AFSC's exosomes on peripheral blood mononuclear cells stimulated with phytohemagglutinin was compared to that of the supernatant produced by such conditioned media deprived of exosomes. We present evidence that the principal effect of AFSC conditioned media (without exosomes) is the induction of apoptosis in lymphocytes, whereas exposure to AFSC-derived exosomes decreases the lymphocyte's proliferation, supporting the hypothesis that the entire secretome of stem cells differently affects immune-response. © 2017 BioFactors, 44(2):158-167, 2018.

Activation of Wnt signaling by amniotic fluid stem cell-derived extracellular vesicles attenuates intestinal injury in experimental necrotizing enterocolitis

“…AFSC, in general, are interesting cells to pursue novel medical investigations and treatment due to their lack of tumorigenicity when injected into immune-compromised animals, making them attractive cells for clinicians and researchers in the field of regenerative medicine and for severe diseases requiring cellular repopulation like NEC 39 – 41 . However, AFSC continue to raise some fear with respect to immunogenicity, and EV can help alleviate this concern 42 . Although EV presents a very interesting potential treatment option for NEC, deciphering how to ensure that administered EV are delivered to the site of injury can be challenging.…”

Combination of Epigallocatechin Gallate and Sulforaphane Counteracts In Vitro Oxidative Stress and Delays Stemness Loss of Amniotic Fluid Stem Cells

“…Human amniotic fluid was collected and processed as previously reported [21]. Human AFSCs were isolated as previously reported [4].…”

“…Cell extracts were obtained as described by Beretti et al [21]. Briefly, subconfluent cells were extracted by the addition of AT lysis buffer (20 mM Tris-Cl, pH 7.0; 1% Nonidet P-40; 150 mM NaCl; 10% glycerol; 10 mM EDTA; 20 mM NaF; 5 mM sodium pyrophosphate; and 1 mM Na 3 VO 4 ) and freshly added protease inhibitor cocktail at 4°C for 30 min.…”

New insights into the immunomodulatory role of exosomes in cardiovascular disease

“…Recent data suggest that the cardiac protective function of stem cells is mainly achieved through paracrine mechanisms (mainly mediated by exosomes) rather than directional differentiation via migration to injury sites (Hashimoto et al, 2018). It is long recognized that exosomes have good stability, biocompatibility, high efficiency, low immunogenicity, and no teratogenicity or embolism risk (Beretti et al, 2018;International Stem Cell Initiative, 2018;Lamichhane et al, 2015;Mentkowski et al, 2018). Hence, they may represent an alternative to stem cell transplantation by circumventing their limitations (Ren, 2018(Ren, , 2019.…”