MSC Treatment Reverses Age-Related Changes in Rats

A recent study examined the effects of injecting rats with mesenchymal stromal cells (MSCs), revealing improvements in aging-related biomarkers and phenotypes across multiple organs ^[1].

The Rejuvenating Role of MSCs

Mesenchymal stromal cells are versatile, originating from sources like bone marrow, adipose tissue, and dental tissues ^[2]. Prior research highlights MSCs' ability to alleviate oxidative stress, promote tissue repair, and extend lifespan and healthspan in mice ^[3][4]. The safety and efficacy of MSCs have been established in clinical trials addressing age-related frailty ^[5].

Positive Impact on Aging Biomarkers

The study focused on the effects of human umbilical cord-derived MSCs (UC-MSCs) on aging in rats. The team administered four weekly injections of UC-MSCs to aged and young male rats. Aged rats showed increased levels of aging-related markers like p16, p21, SA-β-gal, and lipofuscin in multiple organs. Post-treatment, these markers were significantly reduced, indicating a rejuvenating effect of the MSC therapy.

Oxidative Stress Markers:

1. SOD (Superoxide Dismutase): An enzyme that mitigates oxidative damage; its levels were reduced in aged rats but significantly increased after MSC treatment.
2. MDA (Malondialdehyde): A marker of lipid peroxidation and oxidative damage; levels were elevated in aged rats and decreased following treatment.
3. GSH (Glutathione): An antioxidant that showed inconsistent changes across different organs, but MSC treatment generally improved its levels.

Immune System Biomarkers

Aging disrupts immune responses, often marked by changes in IgG, IL-1β, and IL-6 levels. UC-MSC therapy resulted in the following changes:

• IgG: Increased levels were observed in the brain, liver, lungs, kidneys, and blood after treatment.
• IL-1β and IL-6: Elevated in aged rats, these pro-inflammatory cytokines were reduced following MSC therapy, particularly in the lungs, kidneys, and liver.

Rejuvenation of Organs and Microbiome

Brain

The researchers assessed changes in the prefrontal cortex and hippocampus—regions linked to cognitive function and aging ^[6]. MSC treatment led to a significant increase in the number of neurons and improvements in other aging-related phenotypes.

Heart and Liver

The heart showed signs of collagen accumulation and cellular hypertrophy in aged rats, both of which improved with treatment. Additionally, MSC therapy reduced fat deposition in the heart and liver, suggesting an impact on lipid metabolism.

Microbiome

Aging decreases gut microbial diversity ^[7]. In this study, older rats exhibited changes in their microbiomes, which MSC treatment reversed to mirror a more youthful state.

Rejuvenating the Immune System

Aging compromises immune function through immunosenescence. This includes an imbalance in T-cell ratios and reduced spleen cell count. MSC treatment improved these immunological parameters, showing potential for reversing immune aging ^[8].

Comprehensive but Short-Term Study

While the anti-aging benefits of MSCs are documented, this study provides a comprehensive overview of how MSC therapy can modulate aging across the entire organism. However, the long-term effects and mechanisms of action require further investigation.

References:

1. Wang, L., Deng, Z., Li, Y., Wu, Y., Yao, R., Cao, Y., Wang, M., Zhou, F., Zhu, H., & Kang, H. (2024). Ameliorative effects of mesenchymal stromal cells on senescence-associated phenotypes in naturally aged rats. Journal of Translational Medicine, 22(1), 722. ↩︎
2. Galipeau, J., & Sensébé, L. (2018). Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell, 22(6), 824–833. ↩︎
3. He, Y., Chen, D., Yang, L., Hou, Q., Ma, H., & Xu, X. (2018). The therapeutic potential of bone marrow mesenchymal stem cells in premature ovarian failure. Stem Cell Research & Therapy, 9(1), 263. ↩︎
4. Wang, L., Li, Y., Xu, M., Deng, Z., Zhao, Y., Yang, M., Liu, Y., Yuan, R., Sun, Y., Zhang, H., Wang, H., Qian, Z., & Kang, H. (2021). Regulation of Inflammatory Cytokine Storms by Mesenchymal Stem Cells. Frontiers in Immunology, 12, 726909. ↩︎
5. Zhu, Y., Ge, J., Huang, C., Liu, H., & Jiang, H. (2021). Application of mesenchymal stem cell therapy for aging frailty: from mechanisms to therapeutics. Theranostics, 11(12), 5675–5685. ↩︎
6. Satoh, A., Imai, S. I., & Guarente, L. (2017). The brain, sirtuins, and ageing. Nature Reviews. Neuroscience, 18(6), 362–374. ↩︎
7. Claesson, M. J., Jeffery, I. B., Conde, S., Power, S. E., O’Connor, E. M., Cusack, S., Harris, H. M., Coakley, M., Lakshminarayanan, B., O’Sullivan, O., Fitzgerald, G. F., Deane, J., O’Connor, M., Harnedy, N., O’Connor, K., O’Mahony, D., van Sinderen, D., Wallace, M., Brennan, L., Stanton, C., … O’Toole, P. W. (2012). Gut microbiota composition correlates with diet and health in the elderly. Nature, 488(7410), 178–184. ↩︎
8. Goronzy, J. J., & Weyand, C. M. (2013). Understanding immunosenescence to improve responses to vaccines. Nature Immunology, 14(5), 428–436. ↩︎