Stem and progenitor cells hold promise as cell-based therapies in regenerative medicine, but optimal ex vivo culture conditions are key for maximizing their therapeutic potential. Chaurasia et al. studied human umbilical cord blood cells, which are a limited source of haematopoietic stem cells for transplantation into allogeneic recipients that suffer from haematopoietic abnormalities. Testing the effects of various growth factors and small molecules on cord blood cells ex vivo, they found that the histone deacetylase inhibitor (HDACi) valproic acid increased the number of stem cells, upregulated the expression of pluripotency genes and enhanced the repopulation of the haematopoietic system when transplanted into immunodeficient mice. In a separate study, Palii et al. studied human endothelial progenitor cells (EPCs) derived from cord blood for their ability to repair vascular tissue in a mouse model of ischaemic tissue damage. They identified a key role for the transcription factor TAL1 in the repair, which recruits histone acetyltransferase p300 to effector genes. Treatment of EPCs with the HDACi trichostatin A — to mimic TAL1 function — enhanced vascular repair. Overall, chromatin-modulating small molecules could be valuable for optimizing gene expression programmes in stem-cell-based therapy applications, provided that they are safe.
References
Chaurasia, P. et al. Epigenetic reprogramming induces the expansion of cord blood stem cells. J. Clin. Invest. http://dx.doi.org/10.1172/JCI70313 (2014)
Palii, C. G. et al. Trichostatin A enhances vascular repair by injected human endothelial progenitors through increasing the expression of TAL1-dependent genes. Cell Stem Cell 14, 644–657 (2014)
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Burgess, D. Histone deacetylase inhibitors for stem cell boost. Nat Rev Genet 15, 364 (2014). https://doi.org/10.1038/nrg3755
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DOI: https://doi.org/10.1038/nrg3755