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

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 cl...

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Autores principales:	Eleni Anastasiadou, Simona Ceccarelli, Elena Messina, Giulia Gerini, Francesca Megiorni, Paola Pontecorvi, Simona Camero, Maria Giuseppina Onesti, Pankaj Trivedi, Mario Faenza, Enrico Coscioni, Giovanni Francesco Nicoletti, Claudio Napoli, Cinzia Marchese
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/130fb854da61478d8bc50f8d95f23915
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spelling	oai:doaj.org-article:130fb854da61478d8bc50f8d95f239152021-12-02T20:08:11ZMiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.1932-620310.1371/journal.pone.0257070https://doaj.org/article/130fb854da61478d8bc50f8d95f239152021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257070https://doaj.org/toc/1932-6203Adipose-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.Eleni AnastasiadouSimona CeccarelliElena MessinaGiulia GeriniFrancesca MegiorniPaola PontecorviSimona CameroMaria Giuseppina OnestiPankaj TrivediMario FaenzaEnrico CoscioniGiovanni Francesco NicolettiClaudio NapoliCinzia MarchesePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257070 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eleni Anastasiadou Simona Ceccarelli Elena Messina Giulia Gerini Francesca Megiorni Paola Pontecorvi Simona Camero Maria Giuseppina Onesti Pankaj Trivedi Mario Faenza Enrico Coscioni Giovanni Francesco Nicoletti Claudio Napoli Cinzia Marchese MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.
description	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.
format	article
author	Eleni Anastasiadou Simona Ceccarelli Elena Messina Giulia Gerini Francesca Megiorni Paola Pontecorvi Simona Camero Maria Giuseppina Onesti Pankaj Trivedi Mario Faenza Enrico Coscioni Giovanni Francesco Nicoletti Claudio Napoli Cinzia Marchese
author_facet	Eleni Anastasiadou Simona Ceccarelli Elena Messina Giulia Gerini Francesca Megiorni Paola Pontecorvi Simona Camero Maria Giuseppina Onesti Pankaj Trivedi Mario Faenza Enrico Coscioni Giovanni Francesco Nicoletti Claudio Napoli Cinzia Marchese
author_sort	Eleni Anastasiadou
title	MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.
title_short	MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.
title_full	MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.
title_fullStr	MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.
title_full_unstemmed	MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.
title_sort	mir-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/130fb854da61478d8bc50f8d95f23915
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MiR-200c-3p maintains stemness and proliferative potential in adipose-derived stem cells by counteracting senescence mechanisms.

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