An Introduction to Mesenchymal Stem Cells in Regenerative Research

This open access paper provides an introduction to the widespread use of mesenchymal stem cells (MSCs) in regenerative medicine and research. This is one of the better documented stem cell populations. The scientific and medical communities have more experience with these cells than is the case for most other stem cell types, the methodologies for use are more established, and as a consequence MSCs have been and continue to be used in many clinical trials, cell therapies available via medical tourism, and lines of ongoing research. That said, these cells are training wheels in a way, one present step on a longer road. The step is taken because it is convenient and should reliably lead to the next stage in the development of better cell therapies - not because it is the final stopping point.

Being first isolated in 1966 from bone marrow, mesenchymal stem cells (MSC) are adult stromal nonhematopoietic cells, well known for their potential to differentiate into osteoblasts and osteocytes. Although they are most known for their osteogenic differentiation potential, MSC have the ability to commit into all three lineages (osteogenic, chondrogenic, and adipogenic). MSC have been isolated and purified not only from bone marrow where they cooperate with hematopoietic stem cells (HSC) to form the niche, but also from various tissues, such as umbilical cord and umbilical cord blood, white adipose tissue, placenta, and the amniotic membrane of placenta. The capacity of MSC to differentiate into cell lineages and develop teratoma, a preserved tumor that contains normal three-germ layer tissue and organ parts, is a reason to consider them as multipotent progenitor cells suitable for regenerative therapy.

Beside their potential to differentiate into osteoblasts in the process of osteogenesis, there have been several other regenerative roles attributed to MSC. These cells can serve as pericytes wrapping around blood vessels to support their structure and stability. MSC have also shown the potential to integrate into the outer wall of the microvessels and arteries in many organs, such as spleen, liver, kidney, lung, pancreas, and brain. This led to the speculation that both bone marrow- and vascular wall-derived MSC as well as white adipose tissue-, umbilical cord blood-, and amniotic membrane-derived MSC could act as a cell source for regenerative therapy to treat various disorders such as osteoporosis, arthritis, and vessel regeneration after injury.

MSC may also be induced to differentiate into functional neurons, corneal epithelial cells, and cardiomyocytes under specific pretreatments ex vivo and in vivo that broaden the capacity of these cells in regenerative therapeutic interventions. In a previous study, umbilical cord matrix stem cells derived from human umbilical cord Wharton's Jelly were aimed to treat neurodegenerative disorders such as Parkinson's disease by transplantation into the brain of a rat model. The transplantation resulted in a significant reduction of symptoms for Parkinson's disease, thus suggesting an additional therapeutic role for umbilical cord matrix stem cells (MSC) in treating central nervous disorders. Further, MSCs exibit potent immunomodulatory and anti-inflammatory properties through cellular crosstalk and production of bioactive molecules.

These findings were enough evidence for scientists to speculate a promising role for MSC in regenerative therapy. In the past years, MSC have been used in clinical trials aiming for regeneration of tissues such as bone and cartilage as well as treatment of disorders such as spinal cord injury, multiple sclerosis (MS), Crohn's disease, and graft-versus-host disease (GvHD) due to their broad differentiation capacity and potential of hematopoietic cell recruitment. Several clinical trials are running to identify different aspects of MSC application in terms of safety and efficacy, and at the time of writing, a total number of 657 past clinical studies were found that involve mesenchymal stem cells for different clinical phases.



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