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iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs

Mesenchymal stromal cells derived from induced pluripotent stem cells (iMSCs) have been proposed as alternative sources of primary MSCs with various advantages for cell therapeutic trials. However, precise evaluation of the differences between iMSCs and primary MSCs is lacking due to individual vari...

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Autores principales: Lee, Hae-Ri, Kim, Soo, Shin, Sungho, Jeong, Seon-Yeong, Lee, Dae-Won, Lim, Sun-Ung, Kang, Ji Yeon, Son, Mi-Young, Lee, Cheolju, Yu, Kyung-Rok, Kim, Myungshin, Oh, Il-Hoan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821152/
https://www.ncbi.nlm.nih.gov/pubmed/36614321
http://dx.doi.org/10.3390/ijms24010881
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author Lee, Hae-Ri
Kim, Soo
Shin, Sungho
Jeong, Seon-Yeong
Lee, Dae-Won
Lim, Sun-Ung
Kang, Ji Yeon
Son, Mi-Young
Lee, Cheolju
Yu, Kyung-Rok
Kim, Myungshin
Oh, Il-Hoan
author_facet Lee, Hae-Ri
Kim, Soo
Shin, Sungho
Jeong, Seon-Yeong
Lee, Dae-Won
Lim, Sun-Ung
Kang, Ji Yeon
Son, Mi-Young
Lee, Cheolju
Yu, Kyung-Rok
Kim, Myungshin
Oh, Il-Hoan
author_sort Lee, Hae-Ri
collection PubMed
description Mesenchymal stromal cells derived from induced pluripotent stem cells (iMSCs) have been proposed as alternative sources of primary MSCs with various advantages for cell therapeutic trials. However, precise evaluation of the differences between iMSCs and primary MSCs is lacking due to individual variations in the donor cells, which obscure direct comparisons between the two. In this study, we generated donor-matched iMSCs from individual bone marrow-derived MSCs and directly compared their cell-autonomous and paracrine therapeutic effects. We found that the transition from primary MSCs to iMSCs is accompanied by a functional shift towards higher proliferative activity, with variations in differentiation potential in a donor cell-dependent manner. The transition from MSCs to iMSCs was associated with common changes in transcriptomic and proteomic profiles beyond the variations of their individual donors, revealing expression patterns unique for the iMSCs. These iMSC-specific patterns were characterized by a shift in cell fate towards a pericyte-like state and enhanced secretion of paracrine cytokine/growth factors. Accordingly, iMSCs exhibited higher support for the self-renewing expansion of primitive hematopoietic progenitors and more potent immune suppression of allogenic immune responses than MSCs. Our study suggests that iMSCs represent a separate entity of MSCs with unique therapeutic potential distinct from their parental MSCs, but points to the need for iMSC characterization in the individual basis.
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spelling pubmed-98211522023-01-07 iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs Lee, Hae-Ri Kim, Soo Shin, Sungho Jeong, Seon-Yeong Lee, Dae-Won Lim, Sun-Ung Kang, Ji Yeon Son, Mi-Young Lee, Cheolju Yu, Kyung-Rok Kim, Myungshin Oh, Il-Hoan Int J Mol Sci Article Mesenchymal stromal cells derived from induced pluripotent stem cells (iMSCs) have been proposed as alternative sources of primary MSCs with various advantages for cell therapeutic trials. However, precise evaluation of the differences between iMSCs and primary MSCs is lacking due to individual variations in the donor cells, which obscure direct comparisons between the two. In this study, we generated donor-matched iMSCs from individual bone marrow-derived MSCs and directly compared their cell-autonomous and paracrine therapeutic effects. We found that the transition from primary MSCs to iMSCs is accompanied by a functional shift towards higher proliferative activity, with variations in differentiation potential in a donor cell-dependent manner. The transition from MSCs to iMSCs was associated with common changes in transcriptomic and proteomic profiles beyond the variations of their individual donors, revealing expression patterns unique for the iMSCs. These iMSC-specific patterns were characterized by a shift in cell fate towards a pericyte-like state and enhanced secretion of paracrine cytokine/growth factors. Accordingly, iMSCs exhibited higher support for the self-renewing expansion of primitive hematopoietic progenitors and more potent immune suppression of allogenic immune responses than MSCs. Our study suggests that iMSCs represent a separate entity of MSCs with unique therapeutic potential distinct from their parental MSCs, but points to the need for iMSC characterization in the individual basis. MDPI 2023-01-03 /pmc/articles/PMC9821152/ /pubmed/36614321 http://dx.doi.org/10.3390/ijms24010881 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Hae-Ri
Kim, Soo
Shin, Sungho
Jeong, Seon-Yeong
Lee, Dae-Won
Lim, Sun-Ung
Kang, Ji Yeon
Son, Mi-Young
Lee, Cheolju
Yu, Kyung-Rok
Kim, Myungshin
Oh, Il-Hoan
iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs
title iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs
title_full iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs
title_fullStr iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs
title_full_unstemmed iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs
title_short iPSC-Derived MSCs Are a Distinct Entity of MSCs with Higher Therapeutic Potential than Their Donor-Matched Parental MSCs
title_sort ipsc-derived mscs are a distinct entity of mscs with higher therapeutic potential than their donor-matched parental mscs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821152/
https://www.ncbi.nlm.nih.gov/pubmed/36614321
http://dx.doi.org/10.3390/ijms24010881
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