Dataset Information

Survival of aging CD264⁺ and CD264^- populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.

ABSTRACT: In vivo mesenchymal stem cell (MSC) survival is relevant to therapeutic applications requiring engraftment and potentially to nonengraftment applications as well. MSCs are a mixture of progenitors at different stages of cellular aging, but the contribution of this heterogeneity to the survival of MSC implants is unknown. Here, we employ a biomarker of cellular aging, the decoy TRAIL receptor CD264, to compare the survival kinetics of two cell populations in human bone marrow MSC (hBM-MSC) cultures. Sorted CD264⁺ hBM-MSCs from two age-matched donors have elevated β-galactosidase activity, decreased differentiation potential and form in vitro colonies inefficiently relative to CD264^- hBM-MSCs. Counterintuitive to their aging phenotype, CD264⁺ hBM-MSCs exhibited comparable survival to matched CD264^- hBM-MSCs from the same culture during in vitro colony formation and in vivo when implanted ectopically in immunodeficient NIH III mice. In vitro and in vivo survival of these two cell populations were independent of colony-forming efficiency. These findings have ramifications for the preparation of hBM-MSC therapies given the prevalence of aging CD264⁺ cells in hBM-MSC cultures and the popularity of colony-forming efficiency as a quality control metric in preclinical and clinical studies with MSCs.

SUBMITTER: Madsen SD

PROVIDER: S-EPMC6906265 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Survival of aging CD264<sup>+</sup> and CD264<sup>-</sup> populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.

Madsen Sean D SD Jones Sean H SH Tucker H Alan HA Giler Margaret K MK Muller Dyllan C DC Discher Carson T CT Russell Katie C KC Dobek Georgina L GL Sammarco Mimi C MC Bunnell Bruce A BA O'Connor Kim C KC

Biotechnology and bioengineering 20191112 1

In vivo mesenchymal stem cell (MSC) survival is relevant to therapeutic applications requiring engraftment and potentially to nonengraftment applications as well. MSCs are a mixture of progenitors at different stages of cellular aging, but the contribution of this heterogeneity to the survival of MSC implants is unknown. Here, we employ a biomarker of cellular aging, the decoy TRAIL receptor CD264, to compare the survival kinetics of two cell populations in human bone marrow MSC (hBM-MSC) cultur ...[more]

PMID: 31612990

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Project description:Uncultured mesenchymal stromal cells (MSCs) are increasingly used in therapies; however, the effects of donor age on their biological characteristics and gene expression remain unclear. The aim of this study was to investigate age-related changes in bone marrow (BM) MSCs following minimal or no culture manipulation. Iliac crest BM was aspirated from 67 healthy donors (19-89 years old) and directly used for the colony-forming unit-fibroblast (CFU-F) assay or CD45lowCD271+ cell enumeration. The colonies were analysed for colony area and integrated density (ID) when grown in standard MSC media or media supplemented with human serum from young (YS) or old (OS) donors. There was a notable age-related decline in the number of MSCs per millilitre of BM aspirate revealed by the CFU-F assay (r = -0.527, p < 0.0001) or flow cytometry (r = -0.307, p = 0.0116). Compared to young donors (19-40 years old), colony IDs were significantly lower in older donors (61-89 years old), particularly for smaller-sized colonies (42% lower, p < 0.01). When cultured in media supplemented with OS, young and old donor MSCs formed colonies with lower IDs, by 21%, p < 0.0001, and 27%, p < 0.05, respectively, indicating the formation of smaller sparser colonies. No significant differences in the expression of selected adipogenic, osteogenic, stromal, and bone remodelling genes as well as CD295, CD146, CD106, and connexin 43 surface molecules were found in sorted CD45lowCD271+ MSCs from young and old donors (n = 8 donors each). Altogether, these results show similar trends for age-related decline in BM MSC numbers measured by the CFU-F assay and flow cytometry and reveal age-related effects of human serum on MSC colony formation. No significant differences in selected gene expression in uncultured CD45lowCD271+ MSCs suggest that old donor MSCs may not be inferior in regard to their multipotential functions. Due to large donor-to-donor variation in all donor groups, our data indicate that an individual's chronological age is not a reliable predictor of their MSC number or potency.

Dataset Information

Survival of aging CD264⁺ and CD264^- populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.

Publications

Survival of aging CD264<sup>+</sup> and CD264<sup>-</sup> populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.

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Dataset Information

Survival of aging CD264+ and CD264- populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.

Publications

Survival of aging CD264<sup>+</sup> and CD264<sup>-</sup> populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Survival of aging CD264⁺ and CD264^- populations of human bone marrow mesenchymal stem cells is independent of colony-forming efficiency.