A Stem Cell Secretome Treatment Improves Measures of Health in Old Mice

The stem cell therapy industry is evolving. There are a few reasons for this. Firstly, cells remain hard to work with as a basis for therapy, and the level of standardization expected by regulators is very challenging to achieve, even for companies with very deep pockets. In the wilder world of stem cell therapies obtained via medical tourism, outcomes vary broadly from clinic to clinic and patient to patient for reasons that remain unclear. Secondly, stem cell transplantation produces benefits to aged patients primarily via the signaling produced by transplanted cells in a short time prior their destruction, rather than through any other activity of those cells.

Given these points, there is a slow shift away from using cells and towards the use of cell products such as harvested extracellular vesicles or, as in today's open access paper, the secretome of all molecules that exit the cell into extracellular medium, not just those encapsulated in vesicles. Immunis Biomedical is the company involved in the work reported here, working towards the clinical use of stem cell secretome therapies. Primarily this work involves standardization of cell lines and consistency of the resulting harvested secretome to a degree that will satisfy the regulators. Cells are still hard to manage, but compressing down that management into only the centralized process of manufacturing the therapy makes the goal attainable with a reasonable amount of funding.

Stem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice

Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth factors, cytoskeletal remodeling factors, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22-24 months) compared to saline-injected aged-matched controls.

Secretome delivery substantially increased whole-body lean mass and decreased fat mass, corresponding to higher myofiber cross-sectional area and smaller adipocyte size, respectively. Secretome-treated mice also had greater whole-body physical function (grip strength and rotarod performance) and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome-treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, collagen IV turnover, reduced intramuscular lipids, and greater Akt and hormone sensitive lipase phosphorylation in adipose tissue. Finally, secretome treatment in vitro directly enhanced muscle cell growth and IL-6 production, and in adipocytes, it reduced lipid content and improved insulin sensitivity. Moreover, indirect treatment with secretome-treated myotube culture media also enhanced muscle cell growth and adipocyte size reduction.

Together, these data suggest that intramuscular treatment with a stem cell secretome improves whole-body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice.

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