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Cellular Aging Secretes : a Comparison of Bone-Marrow-Derived and Induced Mesenchymal Stem Cells and Their Secretome Over Long-Term Culture

Marote, Ana LU ; Santos, Diogo ; Mendes-Pinheiro, Bárbara ; Serre-Miranda, Cláudia ; Anjo, Sandra I. ; Vieira, Joana ; Ferreira-Antunes, Filipa ; Correia, Joana Sofia ; Borges-Pereira, Caroline and Pinho, Andreia G. , et al. (2023) In Stem Cell Reviews and Reports 19(1). p.248-263
Abstract

Mesenchymal stem cells (MSCs) hold promising therapeutic potential in several clinical applications, mainly due to their paracrine activity. The implementation of future secretome-based therapeutic strategies requires the use of easily accessible MSCs sources that provide high numbers of cells with homogenous characteristics. MSCs obtained from induced pluripotent stem cells (iMSCs) have been put forward as an advantageous alternative to the gold-standard tissue sources, such as bone marrow (BM-MSCs). In this study, we aimed at comparing the secretome of BM-MSCs and iMSCs over long-term culture. For that, we performed a broad characterization of both sources regarding their identity, proteomic secretome analysis, as well as replicative... (More)

Mesenchymal stem cells (MSCs) hold promising therapeutic potential in several clinical applications, mainly due to their paracrine activity. The implementation of future secretome-based therapeutic strategies requires the use of easily accessible MSCs sources that provide high numbers of cells with homogenous characteristics. MSCs obtained from induced pluripotent stem cells (iMSCs) have been put forward as an advantageous alternative to the gold-standard tissue sources, such as bone marrow (BM-MSCs). In this study, we aimed at comparing the secretome of BM-MSCs and iMSCs over long-term culture. For that, we performed a broad characterization of both sources regarding their identity, proteomic secretome analysis, as well as replicative senescence and associated phenotypes, including its effects on MSCs secretome composition and immunomodulatory action. Our results evidence a rejuvenated phenotype of iMSCs, which is translated into a superior proliferative capacity before the induction of replicative senescence. Despite this significant difference between iMSCs and BM-MSCs proliferation, both untargeted and targeted proteomic analysis revealed a similar secretome composition for both sources in pre-senescent and senescent states. These results suggest that shifting from the use of BM-MSCs to a more advantageous source, like iMSCs, may yield similar therapeutic effects as identified over the past years for this gold-standard MSC source. Graphical Abstract: [Figure not available: see fulltext.].

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@article{a3ef1b9c-1637-496c-afec-141da5c51bfe,
  abstract     = {{<p>Mesenchymal stem cells (MSCs) hold promising therapeutic potential in several clinical applications, mainly due to their paracrine activity. The implementation of future secretome-based therapeutic strategies requires the use of easily accessible MSCs sources that provide high numbers of cells with homogenous characteristics. MSCs obtained from induced pluripotent stem cells (iMSCs) have been put forward as an advantageous alternative to the gold-standard tissue sources, such as bone marrow (BM-MSCs). In this study, we aimed at comparing the secretome of BM-MSCs and iMSCs over long-term culture. For that, we performed a broad characterization of both sources regarding their identity, proteomic secretome analysis, as well as replicative senescence and associated phenotypes, including its effects on MSCs secretome composition and immunomodulatory action. Our results evidence a rejuvenated phenotype of iMSCs, which is translated into a superior proliferative capacity before the induction of replicative senescence. Despite this significant difference between iMSCs and BM-MSCs proliferation, both untargeted and targeted proteomic analysis revealed a similar secretome composition for both sources in pre-senescent and senescent states. These results suggest that shifting from the use of BM-MSCs to a more advantageous source, like iMSCs, may yield similar therapeutic effects as identified over the past years for this gold-standard MSC source. Graphical Abstract: [Figure not available: see fulltext.].</p>}},
  author       = {{Marote, Ana and Santos, Diogo and Mendes-Pinheiro, Bárbara and Serre-Miranda, Cláudia and Anjo, Sandra I. and Vieira, Joana and Ferreira-Antunes, Filipa and Correia, Joana Sofia and Borges-Pereira, Caroline and Pinho, Andreia G. and Campos, Jonas and Manadas, Bruno and Teixeira, Manuel R. and Correia-Neves, Margarida and Pinto, Luísa and Costa, Pedro M. and Roybon, Laurent and Salgado, António J.}},
  issn         = {{2629-3269}},
  keywords     = {{Bone marrow; Human platelet lysate; Induced pluripotent stem cells; Mesenchymal stem cells; Replicative senescence; Secretome; Senescence-associated secretory profile}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{248--263}},
  publisher    = {{Springer}},
  series       = {{Stem Cell Reviews and Reports}},
  title        = {{Cellular Aging Secretes : a Comparison of Bone-Marrow-Derived and Induced Mesenchymal Stem Cells and Their Secretome Over Long-Term Culture}},
  url          = {{http://dx.doi.org/10.1007/s12015-022-10453-6}},
  doi          = {{10.1007/s12015-022-10453-6}},
  volume       = {{19}},
  year         = {{2023}},
}