Culturing Mesenchymal Stem Cells for Therapeutic Grade Exosomes
Mesenchymal stem cells secrete tiny extracellular vesicles with big potential for therapeutic applications but choosing the right media to support their production is essential
This article is posted on our Science Snippets Blog
Mesenchymal stem cells (MSCs) are adult stem cells isolated from various sources, such as the bone marrow, adipose tissue, and umbilical cord. They are multipotent cells with the capacity to differentiate into cell types such as osteocytes (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells), and fat cells of adipose tissue (adipocytes) (1). MSCs secrete a host of chemical messengers, including chemokines, cytokines, growth factors, metabolic products, and small molecules such as microRNAs (miRNAs), which act on neighboring cells to produce biological effects (1).
Their potential to differentiate into various cell types and their immunomodulatory functions make MSCs attractive candidates for regenerative therapies and chronic inflammatory disease treatment (1).
What Features of MSCs Make them Attractive Therapeutic Agents?
MSCs influence the morphology and behavior of neighboring cells by secreting extracellular vesicles (EVs). Exosomes are small EVs released from MSC endosomal compartments (1). Exosomes enter circulation and easily shuttle between cells and tissues to deliver MSC-derived components to target cells. Their ability to carry and deliver metabolites, cytokines, miRNAs, proteins, and lipids makes them excellent therapeutic agents (1).
Clinical Potential of Exosomes
Numerous research groups have investigated the therapeutic potential of exosomes for various diseases. MSC-derived exosomal miRNAs protect against reactive oxygen species production and oxidative-stress-induced apoptosis (2). They also mediate therapeutic effects in myocardial infarction and ischemic reperfusion injury via apoptotic pathway suppression (3, 4). Additionally, intranasally administered EVs from human teeth stem cells repair nigrostriatal structures in the brains of rats with Parkinson’s disease, improving memory and gait in these animals (5).
From the Lab to the Clinic
Researchers isolate exosomes from cultured MSCs in the laboratory to explore their therapeutic benefits. However, to translate these practices into therapeutic applications, scientists need to optimize cell culture conditions to yield contamination-free, uniform, and consistent exosome populations. Changes in MSC phenotype can alter the cytokine/chemokine and metabolite profiles of MSCs, resulting in functional changes to their secreted exosomes (6).
One factor that leads to exosome variability is the presence of animal byproducts in cell culture media. Animal byproducts affect the proliferation, differentiation, and phenotypic stability of the MSCs in culture (6).
Sartorius Solution
Scientists at Sartorius developed MSC NutriStem® XF Medium taking into consideration the research needs for developing therapeutic-grade exosomes. MSC NutriStem® XF Medium is a serum-free, xeno-free cell culture medium designed to support stable MSC self-renewal and differentiation into a variety of cell types. Since MSC NutriStem® XF Medium does not have added serum and its associated animal byproducts, it abolishes MSC phenotypic variability, aiding scientists in producing functionally consistent and optimized exosomes for downstream therapeutic applications.
Robust advanced therapies require the design and implementation of efficient and reliable bioprocesses to move from research to clinical phases and eventually gain regulatory approval. A well-defined cell culture medium can strongly influence the productivity of the process and is particularly important for specialized applications such as the harvest of high-quality exosomes for therapeutic purposes.
References
1. Nikfarjam, S., Rezaie, J., Zolbanin, N.M., Jafari, R. Mesenchymal stem cell derived-exosomes: a modern approach in translational medicine. J Transl Med 18, 449 (2020).
2. Li. X., et al. Exosomes from human umbilical cord mesenchymal stem cells inhibit ROS production and cell apoptosis in human articular chondrocytes via the miR-100-5p/NOX4 axis. Cell Biol Int 45(10), 2096-2106 (2021).
3. Peng, Y., et al. Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2. Cell Death Dis 11, 317 (2020).
4. Li, J. W., Wei, L., Han. Z., Chen, Z. Mesenchymal stromal cells-derived exosomes alleviate ischemia/reperfusion injury in mouse lung by transporting anti-apoptotic miR-21-5p. Eur J Pharmacol 852, 68-76 (2019).
5. Narbute, K., et al. Time-dependent memory and gait improvement by intranasally-administered extracellular vesicles in Parkinson’s disease model rats. Cell Mol Neurobiol 41, 605–613 (2021).
6. Bobis-Wozowicz, S., et al. Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles. J Mol Med (Berl) 2, 205-220 (2017).
