Abstract
Mesenchymal stem/progenitor cells (MSC/MPC) are found in many tissues and fluids including bone marrow, adipose tissues, muscle, synovial membranes, synovial fluid, and blood. Such cells from different sources can proliferate and differentiate into different lineages (e.g. osteogenic, chondrogenic and adipogenic) after suitable stimulation. However, details regarding the regulation of MSC/MPC proliferation and differentiation status are still unclear and it is likely that regulation involves both biological and mechanical influences in the different environments. It has been noted that in humans and preclinical animal models that exposure to microgravity/space flight or prolonged bed rest (a surrogate for microgravity) can lead to infiltration of skeletal muscle and bone marrow with fat. Similarly, in preclinical models treated with multiple intramuscular injections of Botulinum Toxin A to induce muscle weakness and atrophy, there is also an infiltration of the muscle with fat. The origins and basis for these fat deposits are largely unknown, but there is a possibility that the altered mechanical and biological environments lead to dysregulation of MSC/MPC and progression to preferential differentiation towards the adipocyte lineage. Furthermore, loss of MSC regulatory control by either mechanical and/or biological factors may also contribute to their involvement in obesity development and progression. Thus, the utility of using MSC/MPC from some sources for tissue engineering purposes may be compromised and further research regarding optimal loading for tissue engineering purposes is likely warranted.
Highlights
Those in the bone marrow appear to prefer to differentiate towards bone cell phenotypes, while those in the synovial membranes or synovial fluid of the knee prefer chondrogenesis ([3] [7]; and others)
The condition has been described, but the source and causes have not been addressed. While this surrogate has been studied in relation to micro-gravity aspects, it is clear that with the aging population, many of whom are confined to prolonged bed rest conditions, there is risk for atrophy and other complications, including “fatty infiltration” of their skeletal muscles and other tissues [41], and some counter measures prevent such accumulation [42]
In the Botulinum toxin studies, the space flight/microgravity studies, and the bed rest studies, as well as other animal studies of weightlessness, an accumulation of fat/lipid infiltrates occurs during prolonged exposure to the altered environment
Summary
Mesenchymal stem/progenitor cells (MSC/MPC) are found in a number of tissues and compartments including blood, placenta, bone marrow, synovial membrane, synovial fluid, fat (infrapatellar fat pad of the knee, subcutaneous fat, abdominal fat) (reviewed in [1] [2]). The MSC/MPC from different tissues and compartments appear to differ with respect to their predilection to differentiate towards different lineages (e.g. bone, cartilage, adipose/fat cells) ([3]; and others).
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