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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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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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On 19 Aug, 2020
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This preprint is under consideration at Immunity & Ageing. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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 Revision
Version 1
Posted 19 Aug, 2020
No community comments so far
Editorial decision: Major Revision
On 25 Jan, 2021
Review #2 received
Received 23 Jan, 2021
Reviewer #2 agreed
On 18 Jan, 2021
Review #1 received
Received 02 Sep, 2020
Reviewer #1 agreed
On 19 Aug, 2020
Reviewers invited
Invitations sent on 19 Aug, 2020
Submission checks complete
On 18 Aug, 2020
Editor assigned
On 18 Aug, 2020
First submitted
On 17 Aug, 2020
Editor invited
On 17 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Immunology
License:
This work is licensed under a CC BY 4.0 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.