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Senescent Mesenchymal Stem Cells: Disease Mechanism and Treatment Strategy
1Laboratory of Molecular Biology and Nanomedicine, Department of Orthopaedics, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA.
Purpose Of Review:
Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic application in tissue engineering and regenerative medicine. Despite their promise, recent findings suggest that MSC replication during repair process may lead to replicative senescence and stem cell exhaustion. Here, we review the basic mechanisms of MSC senescence, how it leads to degenerative diseases, and potential treatments for such diseases.
Recent Findings:
Emerging evidence has shown a link between senescent MSCs and degenerative diseases, especially age-related diseases such as osteoarthritis and idiopathic pulmonary fibrosis. During these disease processes, MSCs undergo cell senescence and mediate Senescence Associated Secretory Phenotypes (SASP) to affect the surrounding microenvironment. Thus, senescent MSCs can accelerate tissue aging by increasing the number of senescent cells and spreading inflammation to neighboring cells.
Summary:
Senescent MSCs not only hamper tissue repair through cell senescence associated stem cell exhaustion, but also mediate tissue degeneration by initiating and spreading senescence-associated inflammation. It suggests new strategies of MSC-based cell therapy to remove, rejuvenate, or replace (3Rs) the senescent MSCs.
Insights
Mesenchymal stem cells (MSCs) can become senescent, hindering tissue repair and promoting degenerative diseases through inflammation. New cell therapies aim to remove, rejuvenate, or replace these senescent MSCs.
Area of Science:
- Biomedical Science
- Cell Biology
- Regenerative Medicine
Background:
- Mesenchymal stem cells (MSCs) are crucial for tissue engineering and regenerative medicine.
- MSC replication during repair can lead to replicative senescence and stem cell exhaustion.
- Senescent MSCs contribute to degenerative and age-related diseases.
Purpose of the Study:
- Review the mechanisms of MSC senescence.
- Understand how MSC senescence contributes to degenerative diseases.
- Explore potential therapeutic strategies for MSC senescence.
Main Methods:
- Literature review of MSC senescence mechanisms.
- Analysis of the link between senescent MSCs and disease.
- Evaluation of therapeutic approaches for senescent MSCs.
Main Results:
- Senescent MSCs are implicated in age-related diseases like osteoarthritis and idiopathic pulmonary fibrosis.
- MSCs undergoing senescence release Senescence Associated Secretory Phenotypes (SASP).
- SASP from senescent MSCs promote inflammation and tissue aging.
Conclusions:
- Senescent MSCs impair tissue repair and drive degeneration via inflammation.
- Strategies to remove, rejuvenate, or replace senescent MSCs are proposed.
- Targeting MSC senescence offers new therapeutic avenues.
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