Jornal de pesquisa e terapia com células-tronco

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Efficiency of Exosome Production Correlates Inversely with the Developmental Maturity of MSC Donor

Tian Sheng Chen, Ronne Wee Yeh Yeo, Fatih Arslan, Yijun Yin, Soon Sim Tan, Ruenn Chai Lai, Andre Choo, Jayanthi Padmanabhan, Chuen Neng Lee, Dominique PV de Kleijn, Kok Hian Tan and Sai Kiang Lim

Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (ESCs) and fetal tissues have been shown to secrete cardioprotective exosome, a protein- and RNA40 containing vesicle. Since the therapeutic efficacy of MSCs is inversely correlated with developmental stage of the donor, we determine if this correlation extended to the cardioprotective MSC exosomes by examining exosomes secreted by MSCs derived from non-embryonic/fetal tissues e.g. umbilical cord. Unlike ESC- and fetal-MSCs, cord-MSCs have a much smaller proliferative capacity. To circumvent this and produce sufficient MSC exosomes for testing, they were immortalized via MYC over-expression. Like ESC-MSCs, MYC immortalization of cord MSCs expanded their proliferative capacity to bypass senescence, reduced plastic adherence, enhanced growth rate, and eliminated in vitro adipogenic differentiation potential without compromising exosome production. Exosomes produced by immortalized cord-MSCs were cardioprotective, and were equally efficacious in reducing infarct size in a mouse model of myocardial ischemia/reperfusion injury. However, cord MSCs produced the least amount of exosomes followed by fetal- and then ESC-MSC in decreasing order of developmental maturity or youth of the donor tissues, suggesting that the inverse correlation between the therapeutic efficacy of MSC and developmental stage of the donor is underpinned by rate of exosome production.