Adipose-derived mesenchymal stem cells (ASCs) are promising therapeutic tools in regenerative medicine because they possess self-renewal, differentiation and immunomodulatory capacities. After isolation, ASCs are passaged multiple times in vitro passages to obtain a sufficient amount of cells for clinical applications. During this time-consuming procedure, ASCs become senescent and less proliferative, compromising their clinical efficacy. Here, we sought to investigate how in vitro passages impact ASC proliferation/senescence and expression of immune regulatory proteins. MicroRNAs are pivotal regulators of ASC physiology. Particularly, miR-200c is known to maintain pluripotency and targets the immune checkpoint Programmed death-ligand 1 (PD-L1). We therefore investigated its involvement in these critical characteristics of ASCs during in vitro passages. We found that when transiently expressed, miR-200c-3p promotes proliferation, maintains stemness, and contrasts senescence in late passaged ASCs. Additionally, this miRNA modulates PD-L1 and Indoleamine 2,3-Dioxygenase (IDO1) expression, thus most likely interfering with the immunoregulatory capacity of ASCs. Based on our results, we suggest that expression of miR-200c-3p may prime ASC towards a self-renewing phenotype by improving their in vitro expansion. Contrarily, its inhibition is associated with senescence, reduced proliferation and induction of immune regulators. Our data underline the potential use of miR-200c-3p as a switch for ASCs reprogramming and their clinical application.

MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms / Anastasiadou, E.; Ceccarelli, S.; Messina, E.; Gerini, G.; Megiorni, F.; Pontecorvi, P.; Camero, S.; Onesti, M. G.; Trivedi, P.; Faenza, M.; Coscioni, E.; Nicoletti, G. F.; Napoli, C.; Marchese, C.. - In: PLOS ONE. - ISSN 1932-6203. - 16:9(2021), pp. 1-17. [10.1371/journal.pone.0257070]

MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms

Anastasiadou E.
Primo
Conceptualization
;
Ceccarelli S.
Methodology
;
Messina E.
Formal Analysis
;
Gerini G.
Investigation
;
Megiorni F.
Investigation
;
Pontecorvi P.
Investigation
;
Camero S.
Investigation
;
Onesti M. G.
Resources
;
Trivedi P.
Investigation
;
Marchese C.
Ultimo
Funding Acquisition
2021

Abstract

Adipose-derived mesenchymal stem cells (ASCs) are promising therapeutic tools in regenerative medicine because they possess self-renewal, differentiation and immunomodulatory capacities. After isolation, ASCs are passaged multiple times in vitro passages to obtain a sufficient amount of cells for clinical applications. During this time-consuming procedure, ASCs become senescent and less proliferative, compromising their clinical efficacy. Here, we sought to investigate how in vitro passages impact ASC proliferation/senescence and expression of immune regulatory proteins. MicroRNAs are pivotal regulators of ASC physiology. Particularly, miR-200c is known to maintain pluripotency and targets the immune checkpoint Programmed death-ligand 1 (PD-L1). We therefore investigated its involvement in these critical characteristics of ASCs during in vitro passages. We found that when transiently expressed, miR-200c-3p promotes proliferation, maintains stemness, and contrasts senescence in late passaged ASCs. Additionally, this miRNA modulates PD-L1 and Indoleamine 2,3-Dioxygenase (IDO1) expression, thus most likely interfering with the immunoregulatory capacity of ASCs. Based on our results, we suggest that expression of miR-200c-3p may prime ASC towards a self-renewing phenotype by improving their in vitro expansion. Contrarily, its inhibition is associated with senescence, reduced proliferation and induction of immune regulators. Our data underline the potential use of miR-200c-3p as a switch for ASCs reprogramming and their clinical application.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1572518
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