Multi-Parameter Analysis of Biobanked Human Bone Marrow Stromal Cells Shows Little Influence for Donor Age and Mild Comorbidities on Phenotypic and Functional Properties

Front Immunol. 2019 Nov 8:10:2474. doi: 10.3389/fimmu.2019.02474. eCollection 2019.

Abstract

Heterogeneous populations of human bone marrow-derived stromal cells (BMSC) are among the most frequently tested cellular therapeutics for treating degenerative and immune disorders, which occur predominantly in the aging population. Currently, it is unclear whether advanced donor age and commonly associated comorbidities affect the properties of ex vivo-expanded BMSCs. Thus, we stratified cells from adult and elderly donors from our biobank (n = 10 and n = 13, mean age 38 and 72 years, respectively) and compared their phenotypic and functional performance, using multiple assays typically employed as minimal criteria for defining multipotent mesenchymal stromal cells (MSCs). We found that BMSCs from both cohorts meet the standard criteria for MSC, exhibiting similar morphology, growth kinetics, gene expression profiles, and pro-angiogenic and immunosuppressive potential and the capacity to differentiate toward adipogenic, chondrogenic, and osteogenic lineages. We found no substantial differences between cells from the adult and elderly cohorts. As positive controls, we studied the impact of in vitro aging and inflammatory cytokine stimulation. Both conditions clearly affected the cellular properties, independent of donor age. We conclude that in vitro aging rather than in vivo donor aging influences BMSC characteristics.

Keywords: bone marrow stromal cell; cellular therapy; comorbidity; in vitro potency assay; in vivo and in vitro aging; mesenchymal stromal cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis
  • Adult
  • Adult Stem Cells / cytology*
  • Adult Stem Cells / immunology
  • Adult Stem Cells / physiology*
  • Aged
  • Aging / immunology
  • Aging / pathology
  • Aging / physiology
  • Biological Specimen Banks
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence / immunology
  • Cellular Senescence / physiology
  • Chondrogenesis
  • Comorbidity
  • Humans
  • Immunophenotyping
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / physiology*
  • Osteogenesis
  • Phenotype
  • Tissue Donors
  • Transcriptome