题名：Extracellular matrix-mediated differentiation of human embryonic stem cells: differentiation to insulin-secreting beta cells.
作者：NARAYANAN K; LIM VY; SHEN J; TAN ZW; RAJENDRAN D; LUO SC; GAO S; WAN AC; YING JY;
来源：Tissue Eng Part A. 2014 Jan;20(1-2):424-33. doi: 10.1089/ten.TEA.2013.0257. Epub [ IF= 0.00 ] ]
摘要：Stem cells have tremendous potential for treating various human diseases.
Protocols have been established to differentiate stem cells into specific
lineages through the provision of signals in the form of growth factors,
cytokines, or small molecules. Herein we investigate an alternative strategy for
directed differentiation of human embryonic stem cells
(hESCs)--extracellular-matrix (ECM) mediated differentiation. Decellularized ECM
and conditioned media from the appropriate committed cell lines are used to
differentiate stem cells to the required phenotype. Applying this strategy to
differentiate hESCs to pancreatic beta cells, we have obtained functional cells
that secreted insulin in a glucose-responsive manner, and were able to recover
normoglycemia in a streptozotocin (STZ)-induced diabetic mouse model.
ECM-mediated differentiation was also demonstrated to be effective for the
differentiation of hESCs into kidney tubule cells and cardiomyocytes. Gene
expression studies suggested the involvement of integrins and catenins in the
beta cell differentiation process; in particular, alpha1, alphav, and beta1
integrins, and beta-catenin showed the highest upregulation. To further elucidate
the biochemical and mechanical cues that have led to effective hESC
differentiation to beta cells, we have employed an artificial system that allowed
for variation of matrix stiffness and combination of individual ECM proteins at
various ratios. The differentiation response of hESCs to the native ECM could be
approximated by optimizing this system.