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Systemic Transplantation of Adult Multipotent Stem Cells Prevents Articular Cartilage Degeneration in a Mouse Model of Accelerated Ageing
Mitra Lavasani
Shirley Ryan AbilityLab
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2179-6947
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This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License
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 - / - mice (a model of Hutchinson-Gilford progeria syndrome, a condition marked by accelerated ageing), prevents ageing-related homeostatic decline of AC.
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. 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.
Keywords
Progeria, Accelerated ageing, Articular cartilage, Adult stem cells, Transplantation, Regenerative medicine
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CURRENT STATUS: Under Review
Version 1
Posted 19 Aug, 2020
No community comments so far
Review #1 received
Received 01 Sep, 2020
Reviewer #1 agreed
On 18 Aug, 2020
Reviewers invited
Invitations sent on 18 Aug, 2020
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On 18 Aug, 2020
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On 17 Aug, 2020
Editor invited
On 17 Aug, 2020
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On 16 Aug, 2020
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Immunology
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This preprint is under consideration at Immunity & Ageing. Preprints are preliminary reports that have not undergone peer review. They should not be considered conclusive, used to inform clinical practice, or referenced by the media as validated information.
Learn more about In Review
Research
Systemic Transplantation of Adult Multipotent Stem Cells Prevents Articular Cartilage Degeneration in a Mouse Model of Accelerated Ageing
Mitra Lavasani
Shirley Ryan AbilityLab
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2179-6947
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 19 Aug, 2020
No community comments so far
Review #1 received
Received 01 Sep, 2020
Reviewer #1 agreed
On 18 Aug, 2020
Reviewers invited
Invitations sent on 18 Aug, 2020
Submission checks complete
On 18 Aug, 2020
Editor assigned
On 17 Aug, 2020
Editor invited
On 17 Aug, 2020
First submitted
On 16 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Immunology
License:
This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License
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 - / - mice (a model of Hutchinson-Gilford progeria syndrome, a condition marked by accelerated ageing), prevents ageing-related homeostatic decline of AC.
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. 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.
Figure 1
Figure 2
Figure 3
Figure 4
Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF.