Age-dependent decrease in the chondrogenic potential of human bone marrow mesenchymal stromal cells expanded with fibroblast growth factor-2

Cytotherapy. 2013 Sep;15(9):1062-72. doi: 10.1016/j.jcyt.2013.03.015. Epub 2013 Jun 22.

Abstract

Background aims: Human bone marrow mesenchymal stromal cells are useful in regenerative medicine for various diseases, but it remains unclear whether the aging of donors alters the multipotency of these cells. In this study, we examined age-related changes in the chondrogenic, osteogenic and adipogenic potential of mesenchymal stromal cells from 17 donors (25-81 years old), including patients with or without systemic vascular diseases.

Methods: All stem cell lines were expanded with fibroblast growth factor-2 and then exposed to differentiation induction media. The chondrogenic potential was determined from the glycosaminoglycan content and the SOX9, collagen type 2 alpha 1 (COL2A1) and aggrecan (AGG) messenger RNA levels. The osteogenic potential was determined by monitoring the alkaline phosphatase activity and calcium content, and the adipogenic potential was determined from the glycerol-3-phosphate dehydrogenase activity and oil red O staining.

Results: Systemic vascular diseases, including arteriosclerosis obliterans and Buerger disease, did not significantly affect the trilineage differentiation potential of the cells. Under these conditions, all chondrocyte markers examined, including the SOX9 messenger RNA level, showed age-related decline, whereas none of the osteoblast or adipocyte markers showed age-dependent changes.

Conclusions: The aging of donors from young adult to elderly selectively decreased the chondrogenic potential of mesenchymal stromal cells. This information will be useful in stromal cell-based therapy for cartilage-related diseases.

Keywords: aging; bone marrow; chondrocytes; differentiation; mesenchymal stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / genetics
  • Adipogenesis / physiology
  • Adult
  • Aged
  • Aged, 80 and over
  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / physiology*
  • Calcium / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Chondrogenesis / genetics
  • Chondrogenesis / physiology*
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Female
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / metabolism*
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology*
  • Middle Aged
  • Osteoblasts / metabolism
  • Osteoblasts / physiology
  • Osteogenesis / genetics
  • Osteogenesis / physiology
  • RNA, Messenger / genetics
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism

Substances

  • Aggrecans
  • COL2A1 protein, human
  • Collagen Type II
  • RNA, Messenger
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Fibroblast Growth Factor 2
  • Alkaline Phosphatase
  • Calcium