Systemic transplantation of adult multipotent stem cells prevents articular cartilage degeneration in a mouse model of accelerated ageing.
Accelerated ageing
Adult stem cells
Articular cartilage
Progeria
Regenerative medicine
Transplantation
Journal
Immunity & ageing : I & A
ISSN: 1742-4933
Titre abrégé: Immun Ageing
Pays: England
ID NLM: 101235427
Informations de publication
Date de publication:
07 Jun 2021
07 Jun 2021
Historique:
received:
17
08
2020
accepted:
26
05
2021
entrez:
8
6
2021
pubmed:
9
6
2021
medline:
9
6
2021
Statut:
epublish
Résumé
Osteoarthritis (OA) is one of the most prevalent joint diseases of advanced age and is a leading cause of disability worldwide. Ageing is a major risk factor for the articular cartilage (AC) degeneration that leads to OA, and the age-related decline in regenerative capacity accelerates OA progression. Here we demonstrate that systemic transplantation of a unique population of adult multipotent muscle-derived stem/progenitor cells (MDSPCs), isolated from young wild-type mice, into Zmpste24 MDSPC treatment inhibited expression of cartilage-degrading factors such as pro-inflammatory cytokines and extracellular matrix-proteinases, whereas pro-regenerative markers associated with cartilage mechanical support and tensile strength, cartilage resilience, chondrocyte proliferation and differentiation, and cartilage growth, were increased. Notably, MDSPC transplantation also increased the expression level of genes known for their key roles in immunomodulation, autophagy, stress resistance, pro-longevity, and telomere protection. Our findings also indicate that MDSPC transplantation increased proteoglycan content by regulating chondrocyte proliferation. Together, these findings demonstrate the ability of systemically transplanted young MDSPCs to preserve a healthy homeostasis and promote tissue regeneration at the molecular and tissue level in progeroid AC. These results highlight the therapeutic potential of systemically delivered multipotent adult stem cells to prevent age-associated AC degeneration.
Sections du résumé
BACKGROUND
BACKGROUND
Osteoarthritis (OA) is one of the most prevalent joint diseases of advanced age and is a leading cause of disability worldwide. Ageing is a major risk factor for the articular cartilage (AC) degeneration that leads to OA, and the age-related decline in regenerative capacity accelerates OA progression. Here we demonstrate that systemic transplantation of a unique population of adult multipotent muscle-derived stem/progenitor cells (MDSPCs), isolated from young wild-type mice, into Zmpste24
RESULTS
RESULTS
MDSPC treatment inhibited expression of cartilage-degrading factors such as pro-inflammatory cytokines and extracellular matrix-proteinases, whereas pro-regenerative markers associated with cartilage mechanical support and tensile strength, cartilage resilience, chondrocyte proliferation and differentiation, and cartilage growth, were increased. Notably, MDSPC transplantation also increased the expression level of genes known for their key roles in immunomodulation, autophagy, stress resistance, pro-longevity, and telomere protection. Our findings also indicate that MDSPC transplantation increased proteoglycan content by regulating chondrocyte proliferation.
CONCLUSIONS
CONCLUSIONS
Together, these findings demonstrate the ability of systemically transplanted young MDSPCs to preserve a healthy homeostasis and promote tissue regeneration at the molecular and tissue level in progeroid AC. These results highlight the therapeutic potential of systemically delivered multipotent adult stem cells to prevent age-associated AC degeneration.
Identifiants
pubmed: 34098983
doi: 10.1186/s12979-021-00239-8
pii: 10.1186/s12979-021-00239-8
pmc: PMC8183038
doi:
Types de publication
Journal Article
Langues
eng
Pagination
27Subventions
Organisme : Christopher L Moseley Foundation
ID : Christopher L Moseley Foundation
Organisme : Lisa Dean Moseley Foundation
ID : Lisa Dean Moseley Foundation
Organisme : Shirley Ryan Abilitylab Innovative Catalyst Award
ID : Shirley Ryan Abilitylab Innovative Catalyst Award
Organisme : RRD VA
ID : IK6 RX003351
Pays : United States
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