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.
