41.3:
Mesenchymal Stem Cells
Mesenchymal stem cells, or MSCs, originate from the embryonic ectoderm and mesoderm, the outer and middle germ layers of a developing embryo. MSCs are multipotent, meaning they can differentiate into multiple connective tissue cell types.
MSCs are similar to fibroblasts in their morphology, gene expression, and differentiation potential, among other characteristics.
MSCs originate as epithelial cells from the epiblast, the developing embryo’s outermost layer. The cells move from the epiblast into a region in the center of the embryo and then migrate laterally as mesenchymal stem cells. The epithelial-to-mesenchymal transition is essential for the formation of various organs and tissues.
Depending on the softness or hardness of the matrix where MSCs are growing, they can differentiate into specific connective tissue cell types.
For example, on a soft extracellular matrix, MSCs differentiate into adipocytes; however, on a much harder matrix, the MSCs differentiate into osteoblasts, potentially forming the bone matrix.
41.3:
Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their access and in vitro expansion and stability have made MSCs the choice of cells in regenerative medicine.
MSCs also show anti-inflammatory and immunomodulatory properties. Immunomodulation is the ability to activate or suppress the immune system to respond to an infection. Immunomodulation is facilitated by extracellular vesicles (EVs) released from MSCs. EVs are reported to efficiently carry molecules such as nucleic acids, proteins, and other paracrine signaling molecules to recipient cells. The EVs can also cross the blood-brain barrier and effectively trigger immune responses. Hence, MSCs and EVs are being investigated for their use as therapeutic agents to treat diseases such as Rheumatoid arthritis and other autoimmune disorders.
While MSCs are explored for their therapeutic potential in repair and regeneration, MSCs also show pro-tumorigenic properties. MSCs secrete growth factors that induce angiogenesis and facilitate tumor growth and invasion, especially when close to other tumor cells. Despite this challenge, MSCs are used as therapeutic agents for cancer treatment. MSCs can inhibit pathways related to the tumor cell cycle or release cytotoxic factors to induce programmed cell death in cancer cells. Thus, MSCs are a ‘double-edged sword’ in cancer treatment.
Suggested Reading
- Ullah, I., Subbarao, R. B., & Rho, G. J. (2015). Human mesenchymal stem cells-current trends and future prospective. Bioscience reports, 35(2), e00191.
- Liu, H., Li, R., Liu, T., Yang, L., Yin, G., & Xie, Q. (2020). Immunomodulatory Effects of Mesenchymal Stem Cells and Mesenchymal Stem Cell-Derived Extracellular Vesicles in Rheumatoid Arthritis. Frontiers in Immunology, 11, 1912.
- Hmadcha, A., Martin-Montalvo, A., Gauthier, B. R., Soria, B., & Capilla-Gonzalez, V. (2020). Therapeutic potential of mesenchymal stem cells for cancer therapy. Frontiers in bioengineering and biotechnology, 8, 43.