Abstract

Due to their self-renewal and differentiation ability, the mesenchymal stem cells (MSCs) have been studied extensively. However, the MSCs lifespan is restricted; they undergo several divisions in vitro that cause several alternations in cellular features and relatively lessens their application. Thus, this study was aimed to assess the effect of platelet-derived microparticles (PMPs), a valuable source of proteins, microRNAs (miRNAs), and growth factors, on the expression of hTERT, c-MYC, p16, p53, and p21 as the most important aging and cell longevity genes alongside with population doubling time (PDT) of PMP-treated cells in comparison to a control group. Umbilical cord MSCs (UC-MSCs) were used in this study, whereby they reached a confluency of 30%. MSCs were treated by PMPs (50 µg/mL), and then, PDT was determined for both groups. Quantitative expression of hTERT, c-MYC, p16, p53, and p21 was examined through quantitative real-time PCR at various intervals (i.e. after five and thirty days as well as freezing-thawing process). Our results demonstrated that the treated group had a shorter PDT in comparison to the control group (P<0.050). The real-Time PCR data also indicated that PMPs were able to remarkably up-regulate hTERT and c-MYC genes expression while down-regulating the expression of p16, p21, and p53 genes (P<0.050), especially following five days of treatment. According to these data, it appears that PMPs are a safe and effective candidate for prolonging the lifespan of UC-MSCs; however, further investigations are needed to corroborate this finding.

Highlights

  • Mesenchymal stem cells (MSCs), defined as nonhematopoietic, multipotential cells, possess self-renewal potential along with the ability to differentiate into mesodermal cells such as bone, cartilage, and fat.[1,2,3] recent studies have provided evidence that mesenchymal stem cells (MSCs) are able to differentiate toward ectodermal and endodermal layers such as liver and neurons.[4]

  • Since MSCs have a limited lifespan, they could enter the process of aging after a number of passages in tissue culture, a phenomenon that is associated with reduced proliferation rate and differentiation potential, morphological changes as well as significantly altered expressions of genes involved in the proliferation and regulation of microRNA levels.[2,4]

  • The present research was designed to investigate the effects of Platelet-derived microparticles (PMPs) as the carrier of growth factors and miRNAs on hTERT, c-MYC, p16, p21 and p53 as the most essential genes required for proliferation and immortalization and to evaluate the potential of PMPs in increasing the longevity of MSCs

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Summary

Introduction

Mesenchymal stem cells (MSCs), defined as nonhematopoietic, multipotential cells, possess self-renewal potential along with the ability to differentiate into mesodermal cells such as bone, cartilage, and fat.[1,2,3] recent studies have provided evidence that MSCs are able to differentiate toward ectodermal and endodermal layers such as liver and neurons.[4]. This study was aimed to assess the effect of platelet-derived microparticles (PMPs), a valuable source of proteins, microRNAs (miRNAs), and growth factors, on the expression of hTERT, c-MYC, p16, p53, and p21 as the most important aging and cell longevity genes alongside with population doubling time (PDT) of PMP-treated cells in comparison to a control group.

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