In their publication in Stem Cell Research & Therapy, a team of researchers has shown how effective mesenchymal stromal cells (MSCs) are in a mouse model.
Multipotent cells with multiple uses
As multipotent stem cells, MSCs can differentiate into several different cell types, including fat cells, neurons, and bone cells [1]. The researchers point to prior studies showing how MSCs have been investigated for the treatment of age-related diseases such as frailty [2]. As the umbilical cord is considered medical waste, umbilical cord-derived cells (here, UC-MSCs) pose no ethical problems in their harvesting and are widely considered a top candidate with which to develop stem cell therapies [3].
Despite their history, the effects of MSCs on diseases such as sarcopenia have never been fully elucidated. This work studied the effects of human cells on SAMP10, a mouse model that is prone to accelerated senescence, to pave the way towards an understanding.
Effects over months
In this research, 24-week-old SAMP10 mice were injected with either one million UC-MSCs or saline solution at the base of the tail. At 28, 32, and 36 weeks, grip strength and treadmill running time were tested. Muscle samples were also taken at 36 weeks, and tests for gene expression and a wide variety of intercellular signaling compounds, such as mTOR and AMPK, were conducted.
Both the grip strength and treadmill results were conclusive. Interestingly, treadmill distance improved in the control mice, but not nearly to the extent of the treatment group; by 36 weeks of age, the treated mice were able to run for one and a half times the distance of their untreated counterparts. In both groups, grip strength also increased at 28 and 32 weeks, and then decreased at 36 weeks; however, the treated mice enjoyed a very large boost to their performance at 28 weeks, which continued throughout the experiment.
Two key muscles, the gastrocnemius and the soleus, were significantly larger in the treated mice than the untreated mice. The treatment made the mice’s muscles visibly thicker and without the voids found in the control group. Their mitochondria were similarly healthier, with fewer visibly damaged mitochondria and lipid droplets.
Compound analysis told a similar story. Among increases in other signaling compounds, the treated mice had more AMPK, which increases NAD+, and mTOR, which, in this context, promotes metabolism and muscular fortitude. They had much less of the inflammatory marker TNF-α and similar biomarkers of inflammaging, along with a reduced expression of compounds that are related to cellular death through apoptosis.
Many other tests told the same story. Every biomarker that the researchers investigated showed signs of the same basic fact: mice given this stem cell therapy had muscles that were significantly stronger and healthier than those of the control group.
Conclusion
One of this study’s limitations was that the researchers were unable to directly discover if the human UC-MSCs had engrafted themselves into the mice’s musculature. However, one examination that they were able to perform, a test for human dystrophin, suggested that this was not the case. Instead, the researchers hypothesize that the positive effects were paracrine in nature: they were due to signals sent by the stem cells instead of the cells themselves being put to work.
While this was a study in a mouse model, the across-the-board positive results suggest a strong potential for therapeutic use in human beings. If these cells, or the paracrine signals they secrete, can be shown to be effective, they might signal a new standard of care for the treatment of sarcopenia and frailty.
Literature
[1] Hsieh, J. Y., Fu, Y. S., Chang, S. J., Tsuang, Y. H., & Wang, H. W. (2010). Functional module analysis reveals differential osteogenic and stemness potentials in human mesenchymal stem cells from bone marrow and Wharton’s jelly of umbilical cord. Stem cells and development, 19(12), 1895-1910.
[2] Golpanian, S., DiFede, D. L., Khan, A., Schulman, I. H., Landin, A. M., Tompkins, B. A., … & Hare, J. M. (2017). Allogeneic human mesenchymal stem cell infusions for aging frailty. The Journals of Gerontology: Series A, 72(11), 1505-1512.
[3] Nagamura-Inoue, T., & He, H. (2014). Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility. World journal of stem cells, 6(2), 195.
