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Clinical Perspective
What is new?
- Adult human skin fibroblasts can be de-differentiated to intermediate CD34+ progenitors
which in turn give rise to endothelial cells as well as erythrocytes
- Lineage conversion of fibroblasts via partial de-differentiation recapitulates in part the
embryonic development of the vasculature as evidenced by upregulation of the anti-aging
enzyme telomerase and the bi-lineage potential of the generated progenitors.
- The transcription factor SOX17 functions as a switch which regulates cell fate of CD34+
progenitors towards an endothelial versus erythroid lineage.
- Implanted fibroblast-derived CD34+ progenitors stably engraft to form functional human
blood vessels in mice that improve cardiac function after myocardial infarction.
What are the clinical implications?
- De-differentiation of fibroblasts to multipotent progenitors can generate patient-specific
functional endothelial cells
- When human fibroblast-derived progenitors are implanted in a mouse model of
myocardial infarction, they are able to improve cardiac function
- The molecular switch SOX17 provides a means to optimize the generation of endothelial
cells for vascular tissue regeneration or disease modeling
- The upregulation of telomerase suggests that fibroblast de-differentiation may avoid
premature aging of the cells during the lineage conversion process which could be
especially helpful when deriving personalized endothelial cells from skin fibroblasts of
older patients
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http://circ.ahajourn...NAHA.116.025722
and:
Protein enables scientists to convert skin to blood vessels
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During the course of the research, the scientists observed increased levels of telomerase –
the anti-ageing enzyme responsible for telomeres on the ends of chromosome – in progenitor cells.
“The increase in telomerase we see in the progenitor cells could be an added benefit of using
this partial de-differentiation technique for the production of new blood vessels for patients
with cardiac disease, especially for older patients,” said Dr Rehman. “The process of converting
and expanding these cells in the lab could make them age even further and impair their long-term
function. But if the cells have elevated levels of telomerase, the cells are at lower risk of
premature ageing.”
INCREASED LEVELS OF TELOMERASE ARE ALSO OBSERVED IN CANCER CELLS, ENABLING CELL DIVISION TO OCCUR AT A VERY HIGH RATE. HOWEVER, THE SCIENTISTS DIDN’T OBSERVE ANY TUMOUR FORMATION DURING THEIR RESEARCH AND THEIR NEXT STEPS WILL INVOLVE FURTHER RESEARCH OVER A LONGER TIME PERIOD IN LARGER ANIMALS.
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http://www.labnews.c...els-10-05-2017/
Importance of this study:
Consolidate the approach using telomerase therapy for rejuvenation: Michael Fossel, Michael West, George Church, Maria Blasco, etc.
