Regulation of differentiation of mesenchymal stem cells into musculoskeletal cells.

Mesenchymal stem cells (MSCs) are multipotent cells that have the capability of differentiating into several different cells such as osteoblasts (bone), chondrocytes (cartilage), adipocytes (fat), myocytes (muscle) and tenocytes (tendon). In this review we highlight the different regulators which determine the lineage a particular MSC will differentiate into. Mesenchymal stem cells are increasingly being used in tissue regeneration and repair. Strict regulation of differentiation of MSCs is essential for a positive outcome of the particular tissue treated with MSCs, especially due to the fact that capacity to differentiate decreases with increasing age of the donor.

Sources of adult mesenchymal stem cells and their applicability for musculoskeletal applications.

There is significant potential for the use of adult mesenchymal stem cells in regenerating musckuloskeletal tissues. The sources of these stem cells discussed in this review are bone marrow, blood, adipose tissue, synovium, periosteum & cartilage. Adult mesenchymal stem cells of bone marrow origin are the cells which are heavily investigated in many studies and have been shown capable of producing a variety of connective tissues especially cartilage and bone. It has recently been suggested that bone marrow derived mesenchymal stem cells originate from microvascular pericytes, and, indeed, many of the tissues from which stem cells have been isolated have good vascularisation and they may give a varied source of cells for future treatments. Clinical trials have shown that these cells are able to be successfully used to regenerate tissues with good clinical outcome. Other sources are showing promise, however, is yet to be brought to the clinical level in humans.

Advances and developments in the use of human mesenchymal stem cells - a few considerations.

One less visited area in musculoskeletal stem cell research is the effects of donor age on quality of stem cells. The prevalence of degenerative orthopaedic conditions is large, and the older population is likely to receive great benefit from stem cell therapies. There are many known growth factors involved in controlling and influencing stem cell growth which are also related to cell senescence. Of which, expressions are found to be altered in mesenchymal stem cells from older donors. Considerations must also be taken of these mechanisms which also have a role in cell cycle and tumour suppression.

The use of growth factors and mesenchymal stem cells in orthopaedics.

Stem cell therapy is an exciting and upcoming branch of tissue engineering with application in the field of orthopaedics. The most commonly used type of stem cells, mesenchymal stem cells (MSCs), can be easily isolated from bone marrow or synovium and cultured in vitro. Newer techniques using tissue engineering to regenerate musculoskeletal tissue by using biomimetic materials are now being studied. These osteoconductive three dimensional constructs seeded with MSCs are highly porous, biodegradable and biomechanically stable scaffolds which do not evoke an immunogenic host cell response. Research has shown the importance of growth factors in guiding and modulating the differentiation of MSCs in order to obtain the required cell type. Gene-based delivery systems have aided the delivery of sustained quantities of these growth factors. The evidence from growth factor enhanced tissue engineering studies for tissue healing looks very positive. This is a multi-disciplinary approach that integrates molecular, biochemical and clinical techniques with developmental and engineering processes. Initial studies indicate an immense potential for cell based strategies to enhance current orthopaedic approaches in skeletal tissue reconstruction. Ultimately, there is a need for randomised controlled trials on human populations to apply these findings to a clinical setting. Nevertheless, stem cell based tissue engineering in orthopaedics shows a promising future.