Neuroprotective effects of human amniotic fluid stem cells-derived secretome in an ischemia/reperfusion model

Abstract

Stem cells offer the basis for the promotion of robust new therapeutic approaches for a variety of human disorders. There are still many limitations to be overcome before clinical therapeutic application, including a better understanding of the mechanism by which stem cell therapies may lead to enhanced recovery. In vitro investigations are necessary to dissect the mechanisms involved and to support the potential development in stem cell-based therapies. In spite of growing interest in human amniotic fluid stem cells, not much is known about the characteristics of their secretome and regarding the potential neuroprotective mechanism in different pathologies, including stroke. To get more insight on amniotic fluid cells therapeutic potential, signal transduction pathways activated by human amniotic fluid stem cells (hAFSCs)derived secretome in a stroke in vitro model (ischemia/reperfusion [I/R] model) were investigated by Western blot. Moreover, miRNA expression in the exosomal fraction of the conditioned medium was analyzed. hAFSCs-derived secretome was able to activate prosurvival and anti-apoptotic pathways. MicroRNA analysis in the exosomal component revealed a panel of 16 overexpressed miRNAs involved in the regulation of coherent signaling pathways. In particular, the pathways of relevance in ischemia/reperfusion, such as neurotrophin signaling, and those related to neuroprotection and neuronal cell death, were analyzed. The results obtained strongly point toward the neuroprotective effects of the hAFSCs-conditioned medium in the in vitro stroke model here analyzed. This can be achieved by the modulation and activation of pro-survival processes, at least in part, due to the activity of secreted miRNAs.

Stem cell secretome derived from human amniotic fluid affords neuroprotection in an ischemic model

“…hAFSCs-derived secretome was observed to initiate pro-survival and anti-apoptotic mechanisms. [ 18 ] After microRNA analysis in the exosomes, it was found that 16 miRNAs were overexpressed and involved in the management of signaling pathways. [ 18 ] The pathways relating to I/R, including neurotrophin signaling, and those associated with neuroprotection and neuronal death, were of particular interest.…”

“…[ 18 ] After microRNA analysis in the exosomes, it was found that 16 miRNAs were overexpressed and involved in the management of signaling pathways. [ 18 ] The pathways relating to I/R, including neurotrophin signaling, and those associated with neuroprotection and neuronal death, were of particular interest. [ 18 ] The evidence compiled proposes that hAFSCs-conditioned medium commences neuroprotective actions within in vitro ischemia models.…”

“…[ 18 ] The pathways relating to I/R, including neurotrophin signaling, and those associated with neuroprotection and neuronal death, were of particular interest. [ 18 ] The evidence compiled proposes that hAFSCs-conditioned medium commences neuroprotective actions within in vitro ischemia models. These observed effects can be achieved through adjusting and initiated pro-survival processes, partially, due to the secreted miRNAs.…”

“…[ 57 ] It was found that CM and more specifically, the exosomal component served an important role in fostering cell survival. [ 18 ] Increased survival was accompanied by suppressing cell-death pathways (p75/JNK) and upregulating pro-growth pathways (BDNF/TrkB). [ 18 ] In addition, pro-survival pathways PI3K/Akt and Erk5 were increased.…”

Exosomes derived from bone marrow mesenchymal stem cells promote angiogenesis via transfer of miR-21-5p after cerebral ischemia in mice

“…The bene cial effects of MSCs-derived Exos on stroke have been particularly studied, but the mechanisms of action are still not fully clari ed [17,18]. Recent studies have shown that Exos transfer miRs to the recipient cells in the brain to affect the nervous and vascular systems, and ultimately alleviate cerebral ischemic injury [19][20][21].…”