Mesenchymal Stem Cells In Bone Augmentation: is It a genuine Contender?

marzo 07, 2018

woman, 8 march, science, stem cells, bone, tissue

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Even to this day, despite the advances in natural and synthetic bone regeneration techniques, autogenous bone grafting remains the gold standard to which all other reconstructive procedures are judged. That being said autogenous bone grafts are not the perfect solution and in fact have several severe limitations - namely the lack of availability of competent sites and the possibility of site complications during the healing process.

On the other hand, a major advantage of bone tissue engineering over autogenous grafting is that it's produced outside of the body (ex vivo) therefore avoiding both availability issues and on-site complications. While the direct delivery of osteogenic cells into the defect site has been proven to work, there remains a stumbling block - the large amount of cells needed, plus of course, the accessibility to them. This is where mesenchymal Stem cells (MSC's) can help.

In a well documented experiment back in 1960 Friedenstein et al, isolated a group of stem cells from bone marrow that went on to form colonies which morphed into osteoblasts. Further studies also proved that collectively, MSC's could be found in fat, lungs, liver, skin, umbilical cord blood, periosteum, and skeletal muscle which can give rise to a selection of other cell types including myoblasts, adipocytes and chondrocytes - so availability should never be an issue.

Despite a wide range of clinical literature documenting how to obtain and grow MSC formations, surprisingly, any literature surrounding MSC-based bone reconstruction techniques are few and far between. What's more, no current reviews of any modern methods have been performed. For this reason a study was commissioned to collate and investigate any clinical and experimental reports of MSC application in the rebuilding of bony defects in live models. These included rats, rabbits, dogs, and humans. Here are the findings...

In 2006 Yuan et al reported that MSC-based bone regenerative capacity was comparable to that of autogenous bone grafting. The clinical trial showed no significant difference between the two methods. In addition, further experimental observations over the next few years showed that the use of MSC's in bony defects increased osteogenetic factors, compared with either untreated defects, or those who received only acellular treatment.

That said, despite several tests indicating distinctive differences, in other trials the results, although favourable, haven't always been statistically significant.

So why is this?

It could be argued that species type has a large part to play in influencing these variances. For example, when rats were given human mesenchymal stem cells using hyaluronic acid as a scaffold an 84% bone regeneration capacity was reported after 4 weeks. The same could be said for human participants where in one clinical study, patients showed adequate bone regeneration when bone marrow stem cells were delivered using a hyaluronic acid/tricalcium phosphate scaffold. This resulted in a 41.43% new bone formation after 3 months. However in rabbits, one experiment utilising human bone marrow stromal cells failed to provoke a positive generative response after 12 weeks compared with autogenous tissue.    

HA-TCP, bone materials, mimetikOss, Bio-Oss

There is also much debate about carrier/scaffold types. For example some clinical trials have delivered success using hyaluronic acid and/or tricalcium phosphate while others have experienced less success. Conversely, other trials have shown significant results when human adipose-derived stem cells (ADSC's) are loaded on poly-lactic co-glycolic acid (PLGA). In another study carried out by Ito et al, it was deemed that fibrin glue was a better carrier for cell delivery compared with micro-porous biphasic calcium phosphate. In another, HA-TCP based carriers performed better than xenographic carriers such as Bio-Oss in both rabbits and in dogs.

What the evidence does show is that while there are many types of carrier or platform for aiding BMSC growth, no single carrier has yet been clinically proven to be head and shoulders above the rest.

The key takeaway

The fact remains that because of the multitude of protocols and the range of parameters more research needs to go into finding the most predictable model of stem cell reconstruction. However after compiling a wide range of studies, it's clear that the advancing science of bone reconstruction using mesenchymal stem cell application techniques, does appear promising.  


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