Because of their unparalleled plasticity and ability to enable tissue homeostasis and repair, which can be exploited for therapeutic applications, Mesenchymal Stem Cells (MSCs) have emerged as a pivotal cell type in regenerative medicine. This multipotency has attracted the attention of scientists and clinicians, with its original discovery coming from bone marrow. Here we will discuss the most significant characteristics of MSCs that make them a major factor in the development of both cell-based therapies and regenerative treatments.
Origin and Sources of MSCs
Mesenchymal stem cells were first described in the bone marrow; however, MSCs have since been identified from a diverse range of tissues (1). These are fat (adipose tissue), umbilical cord blood, dental pulp, and even the placenta. MSCs can be isolated from different sources without inflicting pain to the donor, increasing their importance for research and therapeutic applications.
The first MSCs to be widely investigated were bone marrow-derived MSCs, which are still considered a gold standard for MSC studies. Most human MSCs would still be obtained from bone marrow; however, MSCs from adipose tissue are gaining prominence because harvesting is minimally invasive and higher numbers of cells can be obtained. MSC sources each have their own advantages, but all share a number of defining characteristics that make them valuable in a regenerative medicine context.
Unique Multipotency of MSCs
Among the many intriguing characteristics of MSCs is their ability to differentiate into various specialized cell types. Mesenchymal stem cells (MSCs) have the ability to differentiate into the different cell types of mesodermal origin (osteoblast (bone), chondrocyte (cartilage), and adipocyte (fat)). Due to their multipotency, MSCs can engage in repairing and regenerating numerous tissues, rendering them applicable in a wide variety of potential therapeutic scenarios.
Furthermore, recent studies have proposed that MSCs might be able to differentiate into cells other than those of the mesodermal origin as well including neurons, hepatocytes (liver cells) and cardiomyocytes (heart cells) under certain conditions. Though these features are still under investigation, MSCs demonstrated the potential to cross lineage obstacles emphasizing their plasticity and therapeutic capacity.
Immunomodulatory Properties
MSCs also have impressive immunomodulatory potential. MSCs are known to modulate both the adaptive and the innate immune responses and downregulate the inflammatory response and prevent damage of the tissue by the immune system. These signals include the secretion of bioactive molecules such as cytokines and growth factors that modulate immune cell activity.
Because MSCs can inhibit the activation of T-cells, B-cells and natural killer (NK) cells, they are being studied for use in conditions in which immune activity is excessive (for example, autoimmune diseases). Due to this immunosuppressive characteristic, MSCs are used in allogeneic (donor) transplantations, where immune rejection is a primary concern. That is why MSCs have been investigated as an option to treat graft-versus-host disease (GVHD) and other inflammatory disorders.
Tissue Repair by Paracrine Modulation Without Direct Differentiation
MSCs exert their therapeutic effects via paracrine signaling in addition to differentiation. This means that even in the absence of transdifferentiation, MSCs can still help tissues heal by secreting a cocktail of signaling molecules, including cytokines, growth factors and extracellular vesicles. These molecules stimulate local cells and facilitate reparation through angiogenesis promotion (generation of new blood vessels), apoptosis decrease (programmed cell death), and tissue regeneration improvement.
This paracrine effect allows MSCs to indirectly promote tissue repair, which is a valuable aspect of their regenerative medicine applications, as they do not necessarily need to replace the cell directly. Their communication and influence upon their neighboring cells emphasize their regenerative ability in states such as cardiac infarction, in which direct regeneration may be constrained.
Homing and Engraftment: MSCs Go to Their Destination
This unique ability of MSCs to migrate to sites of injury or inflammation is known as “homing.” Inflamed or damaged tissue expresses the signals necessary to recruit these MSCs to the site of injury, where they can promote healing. One reason MSCs are effective in addressing localized injuries and inflammatory disease, is this homing ability.
Indeed, upon arriving at the site of injury, MSCs develop into a required cell type, or they exert their favorable effects via paracrine mechanisms as previously described. This characteristic makes MSCs a prime candidate for targeted therapies whereby they can migrate to sites requiring repair, without compromising uninjured tissues.
Low Tumorigenic Potential
Here we present the advantages of MSCs over other cell types, including a low risk of tumorigenesis, unlike those associated with embryonic stem cells or induced pluripotent stem cells (iPSCs). It is a significant concern in regenerative medicine where safety is essential. The low tumorigenic potential of MSCs makes them a safer alternative of choice use in cell-based therapies.
Applications in Regenerative Medicine
One of the most promising tools in regenerative medicine is based on the unique combination of multipotency, immunomodulatory properties, paracrine effects and homing abilities that MSCs have. They are under evaluation in clinical trials for many disorders including osteoarthritis, cardiovascular diseases, spinal cord injuries, and autoimmune disorders.
MSCs are used in orthopaedic medicine to repair damaged cartilage and treat broken bones. In cardiology, MSCs have demonstrated promising applications in the repair of heart tissue after myocardial infarction. Moreover, investigations of MSCs as a potential treatments for neurodegenerative conditions, such as Parkinson’s and Alzheimer’s, are under way.
Conclusion
MSCs are very special stem cells as they come in all different shapes and sizes with various biological properties. Their capacity to differentiate into diverse cell types, modulate immune responses, and home to sites of injury renders them promising candidate for broad therapeutic applicability. The future of MSC in regenerative medicine will definitely change with more discoveries and innovations that build on already published evidence.