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Improving Quality and Length of Life with Stem Cells

Mesenchymal stromal cells appear to have broad positive effects.

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Stem Cells for the KneeStem Cells for the Knee

A review article published in Stem Cell Research & Therapy has described the ways in which mesenchymal stromal cells (MSCs) are being developed to treat diseases, including age-related diseases.

A lack of clinical treatments

The reviewers begin their paper by discussing the most common age-related diseases. Immune system problems such as multiple sclerosis [1], brain diseases such as Alzheimer’s [2] and Parkinson’s [3], and metabolic issues such as diabetes [4] and obesity [5] are all linked to aging. While some of these problems have lifestyle-related treatments, many of these diseases lack any effective treatments at all.

The reviewers also spend time discussing cellular senescence and other signifiers of aging. In particular, rather than epigenetics, they focus on physical metrics, such as grip strength, bone health, cognitive function, agility, and respiration. They also note the utility and meaning of chemical biomarkers, such as inflammatory compounds, reactive oxygen species, and the DNA damage marker ฮณH2AX.

These researchers also note the role of stem cell exhaustion, one of the hallmarks of aging, and they characterize one of the prime aspects of aging as being an increase in senescent cells and a loss of healthy replacements [6]. Therefore, this paper focuses around therapies built around stem cells, specifically MSCs, as potential solutions to age-related problems.

MSCs can be taken from a variety of tissues, including bone marrow, fat tissue, and the umbilical cord [7]. The authors outline three factors they deem necessary for the utility of MSCs: they must adhere to a location and grow there, they must express specific molecular antigens on the surface, and they must be able to differentiate into other cellular types.

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Treatments for skin and hair

While age-related hair loss (alopecia) has established treatments, they are of somewhat limited effectiveness. MSCs have significant paracrine effects, which are brought about by the release of factors such as exosomes, that can facilitate hair growth [8]. One study has found that MSCs derived from bone marrow can encourage hair follicle cells to grow instead of rest [9].

Other studies have found that the skin may also be positively affected by MSC-based treatment. The paracrine factors secreted by MSCs discourage the formation of harmful metalloproteinases and improve blood vessel formation [10]. They also help the skin repair after ultraviolet-induced damage, restoring collagen and elastin fibers to the area [11].

Potential benefits for bone, heart, brain, and other tissues

Skin and hair are, of course, only the most visible problems with aging. These reviewers note that MSCs appear to have both direct and paracrine effects on osteoporosis. MSCs can directly differentiate into osteoblasts [12], and the factors that they secrete have been reported to encourage bone repair [13].

One study found that injecting MSCs directly into the knees of aged model mice restored their bone structure and increased their lifespan [14]. While the number of patients was small, a human clinical trial reported some effectiveness in using MSCs to treat spinal fracture in osteoporosis [15].

The same effects appear to be true for cardiovascular diseases. MSCs can directly differentiate into beating heart cells [16] that can be used to develop organoids and potentially replenish depleted tissues, and their paracrine effects have also been reported to positively impact many aspects of cardiac health [17].

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Generation of new neurons normally requires neural stem cells (NSCs) [18], although specific neurons have been reported to be derived from MSCs as well [19]. Unfortunately, while MSCs can secrete anti-inflammatory molecules [20], injecting MSCs into the human brain appears to promote inflammation in practice [21], and more work is being done to alleviate this issue [22].

Positive effects on the kidneys [23], lungs [24], and joints [25] have also been documented.

A potential for lifespan extension

In addition to all the ways in which MSCs might improve health, some research has found that MSCs directly affect lifespan. Most of this research is largely based on extrapolations of its biochemical effects, and other studies are built around mouse models of accelerated aging. However, one human study, the CRATUS study, has found that injection of allogeneic MSCs improves lifespan in frail patients [26]. More studies will need to be done to determine if MSCs improve the lifespan and healthspan of other groups.

In total, however, MSCs and their paracrine exosomes appear to be an extremely valuable tool for researchers and clinicians looking to find ways to extend human life and health. This has gone beyond animal trials and towards the clinic, and we look forward to the full commercialization and broad acceptance of MSC-based therapies that have been proven to be effective.

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Literature

[1] Kritsilis, M., V. Rizou, S., Koutsoudaki, P. N., Evangelou, K., Gorgoulis, V. G., & Papadopoulos, D. (2018). Ageing, cellular senescence and neurodegenerative disease. International journal of molecular sciences, 19(10), 2937.

[2] Grosse, L., Wagner, N., Emelyanov, A., Molina, C., Lacas-Gervais, S., Wagner, K. D., & Bulavin, D. V. (2020). Defined p16High senescent cell types are indispensable for mouse healthspan. Cell Metabolism, 32(1), 87-99.

[3] Kip, E., & Parr-Brownlie, L. C. (2022). Reducing neuroinflammation via therapeutic compounds and lifestyle to prevent or delay progression of Parkinsonโ€™s disease. Ageing Research Reviews, 78, 101618.

[4] Palmer, A. K., Gustafson, B., Kirkland, J. L., & Smith, U. (2019). Cellular senescence: at the nexus between ageing and diabetes. Diabetologia, 62, 1835-1841.

[5] Liu, Z., Wu, K. K., Jiang, X., Xu, A., & Cheng, K. K. (2020). The role of adipose tissue senescence in obesity-and ageing-related metabolic disorders. Clinical science, 134(2), 315-330.

[6] Lรณpez-Otรญn, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023). Hallmarks of aging: An expanding universe. Cell.

[7] Meirelles, L. D. S., Chagastelles, P. C., & Nardi, N. B. (2006). Mesenchymal stem cells reside in virtually all post-natal organs and tissues. Journal of cell science, 119(11), 2204-2213.

[8] Shimizu, Y., Ntege, E. H., Sunami, H., & Inoue, Y. (2022). Regenerative medicine strategies for hair growth and regeneration: A narrative review of literature. Regenerative therapy, 21, 527-539.

[9] Inoue, A., Piao, L., Yue, X., Huang, Z., Hu, L., Wu, H., … & Cheng, X. W. (2022). Young bone marrow transplantation prevents aging-related muscle atrophy in a senescence-accelerated mouse prone 10 model. Journal of Cachexia, Sarcopenia and Muscle, 13(6), 3078-3090.

[10] Jo, H., Brito, S., Kwak, B. M., Park, S., Lee, M. G., & Bin, B. H. (2021). Applications of mesenchymal stem cells in skin regeneration and rejuvenation. International journal of molecular sciences, 22(5), 2410.

[11] Wang, L., Abhange, K. K., Wen, Y., Chen, Y., Xue, F., Wang, G., … & Wan, Y. (2019). Preparation of engineered extracellular vesicles derived from human umbilical cord mesenchymal stem cells with ultrasonication for skin rejuvenation. ACS omega, 4(27), 22638-22645.

[12] Pino, A. M., Rosen, C. J., & Rodrรญguez, J. P. (2012). In osteoporosis, differentiation of mesenchymal stem cells (MSCs) improves bone marrow adipogenesis. Biological research, 45(3), 279-287.

[13] Macรญas, I., Alcorta-Sevillano, N., Rodrรญguez, C. I., & Infante, A. (2020). Osteoporosis and the potential of cell-based therapeutic strategies. International journal of molecular sciences, 21(5), 1653.

[14] Shen, J., Tsai, Y. T., DiMarco, N. M., Long, M. A., Sun, X., & Tang, L. (2011). Transplantation of mesenchymal stem cells from young donors delays aging in mice. Scientific reports, 1(1), 67.

[15] Shim, J., Kim, K. T., Kim, K. G., Choi, U. Y., Kyung, J. W., Sohn, S., … & Han, I. (2021). Safety and efficacy of Wharton’s jelly-derived mesenchymal stem cells with teriparatide for osteoporotic vertebral fractures: A phase I/IIa study. Stem Cells Translational Medicine, 10(4), 554-567.

[16] Metzger, J. M., Samuelson, L. C., Rust, E. M., & Westfall, M. V. (1997). Embryonic stem cell cardiogenesis: applications for cardiovascular research. Trends in cardiovascular medicine, 7(2), 63-68.

[17] Madonna, R., Petrov, L., Teberino, M. A., Manzoli, L., Karam, J. P., Renna, F. V., … & De Caterina, R. (2015). Transplantation of adipose tissue mesenchymal cells conjugated with VEGF-releasing microcarriers promotes repair in murine myocardial infarction. Cardiovascular research, 108(1), 39-49.

[18] Negredo, P. N., Yeo, R. W., & Brunet, A. (2020). Aging and rejuvenation of neural stem cells and their niches. Cell stem cell, 27(2), 202-223.

[19] Singh, M., Kakkar, A., Sharma, R., Kharbanda, O. P., Monga, N., Kumar, M., … & Mohanty, S. (2017). Synergistic effect of BDNF and FGF2 in efficient generation of functional dopaminergic neurons from human mesenchymal stem cells. Scientific reports, 7(1), 10378.

[20] Le Blanc, K., & Ringden, O. (2007). Immunomodulation by mesenchymal stem cells and clinical experience. Journal of internal medicine, 262(5), 509-525.

[21] Kim, H. J., Cho, K. R., Jang, H., Lee, N. K., Jung, Y. H., Kim, J. P., … & Na, D. L. (2021). Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimerโ€™s disease dementia: A phase I clinical trial. Alzheimer’s Research & Therapy, 13(1), 1-11.

[22] Myeong, S. H., Kim, H., Lee, N. K., Hwang, J. W., Kim, H. J., Jang, H., … & Na, D. L. (2022). Intracerebroventricular Administration of Human Umbilical Cord Bloodโ€”Derived Mesenchymal Stem Cells Induces Transient Inflammation in a Transgenic Mouse Model and Patients with Alzheimerโ€™s Disease. Biomedicines, 10(3), 563.

[23] Yun, C. W., & Lee, S. H. (2019). Potential and therapeutic efficacy of cell-based therapy using mesenchymal stem cells for acute/chronic kidney disease. International journal of molecular sciences, 20(7), 1619.

[24] Le Thi Bich, P., Nguyen Thi, H., Dang Ngo Chau, H., Phan Van, T., Do, Q., Dong Khac, H., … & Van Pham, P. (2020). Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study. Stem cell research & therapy, 11(1), 1-14.

[25] Lin, Y. L., Yet, S. F., Hsu, Y. T., Wang, G. J., & Hung, S. C. (2015). Mesenchymal stem cells ameliorate atherosclerotic lesions via restoring endothelial function. Stem cells translational medicine, 4(1), 44-55.

[26] Golpanian, S., DiFede, D. L., Pujol, M. V., Lowery, M. H., Levis-Dusseau, S., Goldstein, B. J., … & Hare, J. M. (2016). Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget, 7(11), 11899.

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About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called โ€œreal life.โ€ Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
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