Early this year, Sophia Chia-Ning Chang and her colleagues experimented on the mesenchymal stem cell (MSC), a type of osteoprogenitor cell, in the hope of testing the feasibility of MSC-facilitated bone formation as a long term method for bone regeneration and substitution. Current methods of bone substitution and implantation all have their shortcomings, whether that be immunological rejection and loosening of the implant in the case of prosthetics and metal, low proliferation rates of periosteal explants and high unattainability of vascularised bone powder, or simply the generally high infection rates associated with the implantation procedures. MSCs encounter none of these difficulties, as often they are able to come directly from the patient him/herself, and they are highly viable as indirect sources of bone matrix.
MSCs work by differentiating into bone-forming osteoblast cells, which then secrete a substance called osteoid which composes the bone matrix. Generally, these osteoblasts are able to form bone in one of two different ways: intramembranous, and endochondral, with the latter type in humans being the more common type of bone formation. Whereas intramembranous bone formation involves direct differentiation of MSCs into osteoblasts, endochondral bone formation involves a preliminary cartilaginous model being formed first in the body, before this model mineralised into woven bone – the first type of bone.
In this experiment, Chang and colleagues implanted a special type of calcium alginate construct, enhanced with MSCs, into the bodies of nude mice. Different concentrations of cells were used in each repetition of the experiment, and these cells were harvested at predetermined times until up to 30 weeks post implantation for histology. Prior to the histological evaluation, the researchers observed that the MSC/alginate constructs grew into highly-cell viable bone-like nodules (see figure) in the host animals’ body, and which were readily accepted into the biological operations of said organisms
From the histological evaluation, the researchers discovered that in this experiment, woven bone, the first type of bone, was surprisingly formed first through endochondral bone formation, as evidenced by the presence of typical endochondrosis in the layout of the woven bone. What this means is that, effectively, an entire step in this particular bone formation process was skipped. This formation of bone in an unexpected way or place - called ectopic formation – could possibly be used for clinical benefit in the future of bone disease or fracture treatment, providing an exciting new glimpse at the potential uses of MSCs in the future.
Additional research that is coming hot on the heels of the aforementioned study includes an experiment performed by a University of Southern California team, which has involved the successful manipulation of MSC viability – achieved by controlling their differentiation mechanism through the growing of these cells on carbon nanotubes.
References:
1)http://docs.google.com/gview?a=v&pid=gmail&attid=0.1&thid=120ffc665709059e&mt=application%2Fpdf,
2) http://www.nature.com/stemcells/2009/0902/090205/full/stemcells.2009.27.html
s4204697
