A research team from the Georgia Institute of Technology Stem has found that stem cells isolated from fat may be a good treatment option for tissue damage and diseases because of their accessibility and lack of rejection. New research published in BioMed Central’s open access journal Stem Cell Research & Therapy shows that this is not as straightforward as previously believed, and that fat-derived stem cells secrete VEGF and other factors, which can inhibit cartilage regeneration. However pre-treating the cells with antibodies against VEGF and growing them in nutrients specifically designed to promote chondrocytes can neutralize these effects.
Adipose Stem Cells and Musculoskeletal Healing
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The researchers found that adipose stem cells (ASCs) secrete large amounts of factors, especially the growth factor VEGF, which prevent cartilage regeneration and actually causes the death (apoptosis) of chondrocytes along with the formation of blood vessels. Treating ASCs with medium designed to encourage their differentiation into cartilage cells was able to reduce the amount of these secreted factors and also prevented the growth of blood vessels. Specifically, an antibody designed to neutralize VEGF prevented chondrocyte apoptosis.
Professor Barbara Boyan, who led this research, explained in the August 23, 2012 news release, “Non-treated ASCs actually impeded healing of hyaline cartilage defects, and although treating ASCs improved the situation they added no benefit to compare to cartilage allowed to heal on its own. However we only looked at cartilage repair for a week after treatment, and other people have shown that two to six weeks is required before the positive effect of ASCs on influence cartilage regeneration is seen.”
Asked what is the most important thing for orthopedists to know about this work, Dr. Boyan told OTW,
Multipotent stem cells are present in fat and have great potential as therapeutics for treating musculoskeletal conditions, but we need to understand much more about them before we use them clinically. While we can manipulate them in many ways in cell culture, their behavior in tissue may be very different than the intended outcome. There is still much to learn.
As for where they go from here, Dr. Boyan stated,
We are studying methods for controlling the delivery of stem cells to treatment sites and for ensuring that the intended clinical outcome can be achieved.
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Discussion
This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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