Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty
Abstract
:1. Introduction
2. Aging in Muscle
2.1. Loss of Muscle Mass
2.1.1. Atrophy of Muscle Fibers
2.1.2. Loss of Muscle Fibers
2.1.3. Reduced Number of Satellite Cells
2.2. Changes in Muscle Function
2.3. The Muscle-Bone Relationship and Aging
3. Aging in Bone
3.1. Gonadocorticoids and Age-Associated Hypogonadism
3.2. Diminished Osteoblast Viability
3.3. Increased Osteoclast Activity
4. Mesenchymal Stem Cells Transplantation for Musculoskeletal Aging Frailty
4.1. Mesenchymal Stem Cells (MSCs)
4.2. Mechanism of Actions of MSCs
4.2.1. Immunomodulatory Properties of MSC Facilitate Allogeneic Transplantation
4.2.2. Exosomes and Extracellular Vesicles
4.2.3. Mitochondrial Transfer
4.3. MSCs to Treat Musculoskeletal Frailty
5. Limitations and Future Perspectives
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Frailty Symptoms | Potential MSC Effects | Potential Mechanisms | References |
---|---|---|---|
Unintentional weight loss | ↓ chronic inflammation | ↓ chronic inflammation (↓ TNF-α, ↓ CRP, ↓ IL-1, ↓ IL-6, ↑ TGF-β), ↓ onset of sarcopenia | Jacobs et al. (2013) [119] |
A feeling of fatigue | ↓ chronic inflammation, ↑ pulmonary function | ↓ chronic inflammation (↓ TNF-α, ↓ CRP, ↓ IL-1, ↓ IL-6, ↑ TGF-β), ↑ endothelial function, ↑ pulmonary function (FEV1) | Jacobs et al. (2013) [119] |
Muscle loss and weakness | ↑ physical activity (six-minute walk distance) | ↑ skeletal muscle performance, ↑ cardiac function performance, ↓ onset of sarcopenia, ↑ endothelial function | Fried et al. (2001) [117] |
Slow walking speed | ↑ physical activity (six-minute walk distance), ↑ pulmonary function | ↑ skeletal muscle performance, ↑ cardiac function performance, ↑ pulmonary function (FEV1), ↑ endothelial function | Fried et al. (2001) [117] |
Low levels of physical activity | ↓ chronic inflammation, ↑ physical activity (six-minute walk distance), ↑ quality of life | ↓ chronic inflammation (↓ TNF-α, ↓ CRP, ↓ IL-1, ↓ IL-6, ↑ TGF-β), ↑ skeletal muscle performance, ↑ cognitive status | Jacobs et al. (2013) [119] |
References | Human Subjects | MSC and Dosage | Results (Related to Musculoskeletal System and Physical Frailty) |
---|---|---|---|
Golpanian et al. (2017) [143] | An average age of 78.4 ± 4.7 years and Clinical Frailty Score of 4–6 | Group 1 = 20 × 106 allo-hBM-MSCs, IV injection | No treatment-emergent serious adverse events (TE-SAEs) were reported with any of the doses at 1-month. |
Group 2 = 100 × 106 allo-hBM-MSCs, IV injection | Six-min walk distance significantly increased at 3 and 6 months in all treatment groups. | ||
Group 3 = 200 × 106 allo-hBM-MSCs, IV injection | Physical component of the SF-36 quality of life assessment also showed significant improvements in the 100-million dose group at all time points relative to baseline. | ||
Tompkins et al. (2017) [144] | Age ≥60 and ≤95 years with Clinical Frailty Score of 4–7 | Group 1 = 100 × 106 allo-hBM-MSCs, IV injection | No therapy-related TE-SAEs reported at 1-month post-infusion. |
Group 2 = 100 × 106 allo-hBM-MSCs, IV injection | Six-min walk test and short physical performance exam improved significantly in the 100-million dose group but not in the 200-million dose or placebo groups. |
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Mahindran, E.; Law, J.X.; Ng, M.H.; Nordin, F. Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty. Int. J. Mol. Sci. 2021, 22, 10542. https://doi.org/10.3390/ijms221910542
Mahindran E, Law JX, Ng MH, Nordin F. Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty. International Journal of Molecular Sciences. 2021; 22(19):10542. https://doi.org/10.3390/ijms221910542
Chicago/Turabian StyleMahindran, Elancheleyen, Jia Xian Law, Min Hwei Ng, and Fazlina Nordin. 2021. "Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty" International Journal of Molecular Sciences 22, no. 19: 10542. https://doi.org/10.3390/ijms221910542