Adult Tissue Extracellular Matrix Determines Tissue Specification of Human iPSC‐Derived Embryonic Stage Mesodermal Precursor Cells

作者：Imran Ullah, Jonas Felix Busch, Anja Rabien, Bettina Ergün, Christof Stamm, Christoph Knosalla, Stefan Hippenstiel, Petra Reinke, Armin Kurtz · 发表于：Advanced Science · 年份：2020 · DOI：10.1002/advs.201901198 · 被引用次数：51 · 研究领域：Tissue Engineering and Regenerative Medicine、Pluripotent Stem Cells Research、Electrospun Nanofibers in Biomedical Applications

The selection of pluripotent stem cell (PSC)-derived cells for tissue modeling and cell therapy will be influenced by their response to the tissue environment, including the extracellular matrix (ECM). Whether and how instructive memory is imprinted in adult ECM and able to impact on the tissue specific determination of human PSC-derived developmentally fetal mesodermal precursor (P-meso) cells is investigated. Decellularized ECM (dECM) is generated from human heart, kidney, and lung tissues and recellularized with P-meso cells in a medium not containing any differentiation inducing components. While P-meso cells on kidney dECM differentiate exclusively into nephronal cells, only beating clusters containing mature and immature cardiac cells form on heart dECM. No tissue-specific differentiation of P-meso cells is observed on endoderm-derived lung dECM. P-meso-derived endothelial cells, however, are found on all dECM preparations independent of tissue origin. Clearance of heparan-sulfate proteoglycans (HSPG) from dECM abolishes induction of tissue-specific differentiation. It is concluded that HSPG-bound factors on adult tissue-derived ECM are essential and sufficient to induce tissue-specific specification of uncommitted fetal stage precursor cells.