Mesenchymal stem cells (MSCs) have inspired a great deal of activity as a novel therapeutic approach. Presently, MSC-based clinical trials are being conducted for a variety of disease conditions, with many trials demonstrating safety and efficacy.
Clinical utility of MSCs can be attributed to four key biological properties:
- Their potential to migrate to sites of inflammation caused by tissue injury when injected intravenously
- Their potential to differentiate into different cell types
- Their potential to release different bioactive molecules that can stimulate the recovery of injured cells
- Their ability to modulate inflammation and accomplish immunomodulatory functions
Currently, several hundred MSC clinical trials are in progress across different parts of the world, including within the U.S. European Union (EU), China, Middle East, and South Korea. Among these clinical trials, approximately one-third are exploiting MSCs for various disease indications. Unfortunately, only a small number of clinical trials using MSCs have reached Phase III, indicating that the therapeutic potential for MSCs has yet to be realized.
One of the major bottlenecks to the industry is how to manufacture clinical-grade MSCs on a commercial scale, which Australian regenerative medicine company Cynata Therapeutics (ASX:CYP) is aiming to solve.
To fully understand the cell type and its evolution over time, this post considers key dates in the discovery of mesenchymal stem cells (MSCs).
The History of Mesenchymal Stem Cells (MSCs)
In 1924, the Russian-born researchers Alexander Maximow used histology to identify a type of precursor cell within the mesenchyme that could differentiate into a variety of blood cell types.1 While the term mesenchymal stem cell did not exist, this is the earliest known reference to the cell type.
Nearly 40 years later, in the 1960’s, researchers Ernest McCulloch and James Till identified the clonal qualities of marrow cells.2,3
It then took another decade until an ex vivo assay was developed that allowed for examination of the clonal nature of multipotent marrow cells.4 This assay was developed by Friedenstein’s team of researchers in the 1970’s, although the stromal cells of interest (now called mesenchymal stem cells) were referred as colony-forming unit-fibroblasts (CFU-f).5
Although the first clinical trials of MSCs occurred in 1995, hundreds of clinical trials have since been initiated.6 Interestingly, it took until the turn of the century (2000) for research supply companies to give enough credibility to the cell type to product research tools to support investigation within the scientific community.
Later research and experimentation further characterized the plasticity of marrow cells and how their differentiation into mature cell types could be manipulated by environmental stimuli. For instance, growing marrow stromal cells in the presence of osteogenic stimuli, such as inorganic phosphate, ascorbic acid, dexamethasone, and related stimuli, can drive differentiation into osteoblasts (bone producing cells). Similarly, the presence of transforming growth factor-best (TGF-b) has the ability to chondrogenic (cartilaginous) traits.
A summary of the most important dates in the discovery of mesenchymal stem cells is presented below.
FIGURE. Key Dates in the Discovery of Mesenchymal Stem Cells
To learn more about mesenchymal stem cells, view the global strategic report , “Mesenchymal Stem Cells – Advances & Applications.”
FOOTNOTES:
1 Wan C, He Q, McCaigue M, Marsh D, Li G (2006). “Nonadherent cell population of human marrow culture is a complementary source of mesenchymal stem cells (MSCs)”.Journal of Orthopaedic Research 24 (1): 21–8.
2 Becker AJ, McCULLOCH EA, Till JE (1963). “Cytological Demonstration of the Clonal Nature of Spleen Colonies Derived from Transplanted Mouse Marrow Cells”. Nature 197(4866): 452–4.
3 Siminovitch L, Mcculloch EA, Till JE (1963). “The distribution of colony-forming cells among spleen colonies”. Journal of Cellular and Comparative Physiology 62 (3): 327–36.
4 Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luriá EA, Ruadkow IA (1974). “Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method”. Experimental hematology 2 (2): 83–9.
5 Friedenstein AJ, Gorskaja JF, Kulagina NN (1976). “Fibroblast precursors in normal and irradiated mouse hematopoietic organs”. Experimental hematology 4 (5): 267–74.
6 Wang S et al. (2012). “Clinical applications of mesenchymal stem cells”. Jour of Hematology and Oncology (19).