Systemic transplantation of adult multipotent stem cells functionally rejuvenates aged articular cartilage

Seth D. Thompson, Rajeswari Pichika, Richard L. Lieber, G. R.Scott Budinger, Mitra Lavasani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Osteoarthritis (OA) is the most common and debilitating joint disease of advanced age and has no universally effective therapy. Here, we demonstrate that systemic transplantation of adult multipotent muscle-derived stem/progenitor cells (MDSPCs)-isolated from young mice-rejuvenates the knee articular cartilage (AC) of naturally aged mice. This intervention reduced expression of pro-inflammatory cytokines (Tnf and Il1a) and catabolic matrix-degrading proteinases (Mmp3 and Mmp13) in aged cartilage. Treatment with young MDSPCs also increased expression of pro-regenerative (Col2a1 and Acan) and prolongevity genes (Pot1b), including those associated with chondrocyte proliferation and differentiation, cartilage growth, and telomere protection. Indeed, the AC of MDSPC-treated mice exhibited reduced age-related histological pathologies. Importantly, the reduced mobility and arthritis-related gait dysfunctions of aged mice were also ameliorated by this treatment. Together, our findings demonstrate the rejuvenating effects of systemic transplantation of young MDSPCs on aging AC-at the molecular, tissue, and functional levels. This suggests that MDSPCs, or their secreted factors, may represent a novel therapy that can increase mobility and function in aged or OA patients.

Original languageEnglish (US)
Pages (from-to)726-731
Number of pages6
JournalAging and Disease
Volume12
Issue number3
DOIs
StatePublished - Jun 1 2021

Keywords

  • Adult stem cells
  • Aging
  • Articular cartilage
  • Gait
  • Regenerative medicine
  • Transplantation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cell Biology

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