One Molecule Commands Stem Cells: “Build Bone!”
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" data-large-file="https://i0.wp.com/ryortho.com/wp-content/uploads/2016/09/OneMolecule_ShyniVarghese_WEB.jpg?fit=220%2C232&ssl=1" src="https://i0.wp.com/ryortho.com/wp-content/uploads/2016/09/OneMolecule_ShyniVarghese_WEB.jpg?resize=220%2C232&ssl=1" alt="Shyni Varghese, Ph.D. / Courtesy of UC San Diego " width="220" height="232">Shyni Varghese, Ph.D. / Courtesy of UC San Diego
It turns out, say researchers at the University of California (UC) San Diego, that a molecule occurring naturally in the body can encourage human pluripotent stem cells to regenerate bone tissue. Known as adenosine, the molecule helped repair cranial bone defects in mice without developing tumors or causing infection.
“One of the broader goals of our research is to make regenerative treatments more accessible and clinically relevant by developing easy, efficient and cost-effective ways to engineer human cells and tissues, ” said Shyni Varghese, Ph.D., a bioengineering professor at UC San Diego and senior author of the study, in the August 31, 2016 news release.
“Another challenge is producing stem-cell-derived tissues or organs that don’t develop teratomas—tumors that contain a variety of tissues found in different organs—when transplanted. Teratomas are what can happen when some of the pluripotent stem cells go rogue and differentiate uncontrollably.”
“Like living bone cells in the body, the resulting osteoblasts built bone tissues with blood vessels. When transplanted into mice with bone defects, the osteoblasts formed new bone tissues in vivo without any signs of teratoma formation.”
Dr. Varghese told OTW, “This work stems from our previous study, which investigated how calcium phosphate minerals found in bone tissue induce stem cells to differentiate into osteoblasts. We have identified that stem cells take up calcium phosphate to produce ATP, a metabolic molecule, which then breaks down into adenosine and functions as an autocrine or paracrine molecule and signals the stem cells to become osteoblasts.
“Our study shows that adenosine can be used to derive large numbers of osteoblasts from hESCs [human embryonic stem cells] and hiPSCs [human induced pluripotent stem cells]. These hESC- and hiPSC-derived osteoblasts contribute to bone tissue formation and treat critical sized bone defects.”
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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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