期刊
AGING AND DISEASE
卷 12, 期 3, 页码 726-731出版社
INT SOC AGING & DISEASE
DOI: 10.14336/AD.2020.1118
关键词
aging; articular cartilage; adult stem cells; transplantation; regenerative medicine; gait
资金
- United States Department of Veterans Affairs RD Service [IK6 RX003351]
- NIA [P01 AG049665]
- Christopher L. Moseley Foundation
- Lisa Dean Moseley Foundation
- Shirley Ryan AbilityLab Innovative Catalyst Grant
Transplantation of young MDSPCs rejuvenates aging knee cartilage by reducing inflammation, promoting regenerative genes, and improving mobility and arthritis-related gait dysfunctions in aged mice. This suggests that MDSPCs may represent a novel therapy to increase mobility and function in aged or OA patients.
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.
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