What could be the mechanism by which mesenchymal stem cells would be involved in cartilage defects like osteoarthritis?Is it a percentage engraftment and forming cartilage?Or is it by a 'hit and run' mechanism through a paracrine effect?With their secretion of anti-inflammatory cytokines they could probably decrease the inflammation temporarily but could they engraft and differentiate?
There have been few clinical trials relating to bmsc therapy for cartilage repair. My colleagues and I are about to begin a clinical trial comparing autologous bmsc's with autologous chondrocytes (either alone or in combination with each other) to try and elucidate the "best" cell for defect repair. Within this trial we hope to investigate the mechanisms by which bmsc's contribute to the repair process. There was a paper published in 2010 by nedjadnik et al who compared a cohort of patients treated with bmsc's with those treated with conventional ACI, you might find it an interesting read.
It is believed that due to they're multipotent lineage that the bmsc's may well be better suited for the treatment of osteochondral defects in OA and in vitro co-culture studies with bmsc's and chondrocytes have demonstrated enhanced cartilage formation and collagen II production.
I'm sorry this doesn't answer your question entirely.........but I hope you find it useful :)
Helen x
Thank you Helen for your feedback.It has definitely answered some other questions in my mind.I am still curious about your hypothesis about the action of BM-MSCs you would have thought of for the clinical trial.
.The exact mechanism by which the MSCs function in an arthritic setting is not defined.My curiosity lies in knowing the exact mechanism of how MSCs function when transplanted.I have a few question open for answers:-
A.Do you think they will engraft better with a simple injection or will it be effective if they are implanted through ACI?
B.In your experience what could be the role of sulphated glycosaminoglycans?Could the measure of GAGs correlate directly to collagen formation?
C.Will MSCs home and engraft into the affected region and engraft?What happens with autologous chondrocytes?Do they engraft?
D.In co-culture,are the chondrocytes derived from the arthritic knee revive significant collagen levels?
Dear Charan Thej!
My PhD work was concerned with both MSCs and chondrocytes in the context of Osteoarthritis (OA).
I agree with Helen McCarthy that the unique nature of MSCs make them the most promising candidates to repair the damaged tissues. However, there is one thing that I would like to highlight pertaining to the cartilage tissue.
Remember that cartilage tissue is avascular, alymphatic and aneural. So migration of MSCs is not quite easy here as in the case of other tissues. Now, here comes the role of regenerative medicine. A lot of clinical trials have been published in this regard.
When you differentiate MSCs in vitro you have to provide certain ingredients in the medium such as TGF-beta. The similar sort of thing happens in vivo when MSCs are implanted into the joint. For the purpose of implantation different methods exists which resemble the same approach used in ACI.
Measuring GAGs is vital if you want to analyze the cartilage repair. Studies concerning the implantation of MSCs have reported that transplantation of MSCs certainly improve the production of proteoglycans and collagens.
Your concern about engraftment of the implanted cells is quite interesting. In my study I observed that both MSCs and chondrocytes home in the knees of rat model of OA. I have not come across a clinical trial that clearly showed the engraftment of transplanted cells through a proper method such as PKH26 dye. However, there are a lot of clinical trials and case studies that report implantation of either MSCs or chondrocytes along with controls. So, improvement in the experimental group certainly indicates improvement due to the implanted cells rather than the native population.
In our lab, co-culture of MSCs and chondrocytes implanted into the rat model of OA showed significant improvement. Chondrocytes obtained in our case were from a normal animal. I am not sure how the same thing will work in the case of arthritic knee. Generally in humans, sample of cartilage is taken from the non-weight bearing areas of the joint, and studies indicate that the cells obtained from these areas yielded phenotypically normal chondrocytes. Remember again that cartilage is avascular tissue. So, damage at one site in the tissue does not spread in the same manner as in other tissues of the body.
I hope my answer may help you a little bit. If it does it is my pleasure.
Regards,
Fazal-ur-Rehman Bhatti,
National Centre for Excellence in Molecular Biology,
University of the Punjab, Lahore, Pakistan.
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