Heterogeneity of Mesenchymal Stem Cells in Cartilage Regeneration

Articular cartilage, found on the surface of most musculoskeletal joints, distributes and transfers forces between bones and joints, provides a smooth surface for joint mobility, and plays an important role in human mobility. 

However, articular cartilage is also easily susceptible to damage, but difficult to repair itself on its own (primarily due to the fact it is mostly avascular). Over time, the inability of articular cartilage to repair itself leads to progressive joint pain, disfigurement, movement disorders, and ultimately osteoarthritis.

The CDC estimates that nearly 33 million Americans are currently affected by osteoarthritis, most often in the form of pain, stiffness, decreased mobility and range of motion, and swelling in the joints^[1].

Current treatment methods, including microfracture technology, autologous or allogeneic cartilage transplantation, and autologous chondrocyte implantation (ACI) have demonstrated the ability to repair and regenerate fibrous cartilage, but not articular cartilage required for smooth, fluid, natural mobility.

To address this issue, recent research has focused on the efficacy of stem cells, and specifically mesenchymal stem cells (MSCs) found in bone marrow, adipose tissue, synovial membrane, and umbilical cord Wharton’s jelly, as potential therapeutic treatments for regeneration of articular cartilage. MSCs are particularly of interest due to their demonstrated abilities of self-renewal, multi-differentiation, and immunoregulation.

While the use of MSCs has demonstrated tremendous potential in the field of regenerative therapy, one notable drawback continues to be unstable or suboptimal results resulting from the heterogeneity of various mesenchymal stem cells.

Specifically, the stability and efficacy of MSCs appear to differ based on a number of factors, including the donor, the tissue source, and their ability for proliferation, differentiation, and immunoregulation.

For example, some of the key heterological differences highlighted in this review include the efficacy of MSCs based on donor’s age (with younger donors providing higher quality MSCs), Wharton’s Jelly MSCs showing greater prospects for application in cartilage regeneration than other MSCs, and differences within specific MSC subpopulations. 

The authors of this review acknowledge the potential of MSCs in repairing arterial cartilage, but also point out that there needs to be a deeper understanding of the heterogeneity of various MSCs in order to improve the efficiency of MSC-based therapies designed to repair arterial cartilage.  In addition, the authors also call for greater standardization in MSC isolation and harvesting methods among laboratories in order to provide better consistency with respect to results obtained from studies using MSCs.

Source:  “Heterogeneity of mesenchymal stem cells in cartilage regeneration.” 19 Mar. 2021, https://www.nature.com/articles/s41536-021-00122-6?elqTrackId=5517bd20493b470cb34fd0e8bc1f6ef9.

^[1] “Osteoarthritis (OA) | Arthritis | CDC.” https://www.cdc.gov/arthritis/basics/osteoarthritis.htm.