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成人组织细胞外基质决定人诱导多能干细胞衍生的胚胎期 mesodermal 前体细胞的组织特异性。

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

作者信息

Ullah Imran, Busch Jonas Felix, Rabien Anja, Ergün Bettina, Stamm Christof, Knosalla Christoph, Hippenstiel Stefan, Reinke Petra, Kurtz Andreas

机构信息

Berlin Institute of Health Center for Regenerative Therapies Charité Universitätsmedizin Berlin Augustenburger Platz 1 13353 Berlin Germany.

Department of Urology Charité-Universitätsmedizin Berlin 10117 Berlin Germany.

出版信息

Adv Sci (Weinh). 2020 Jan 21;7(5):1901198. doi: 10.1002/advs.201901198. eCollection 2020 Mar.

DOI:10.1002/advs.201901198
PMID:32154066
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7055561/
Abstract

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.

摘要

用于组织建模和细胞治疗的多能干细胞（PSC）衍生细胞的选择将受到它们对组织环境（包括细胞外基质（ECM））反应的影响。研究了指导性记忆是否以及如何印记在成人ECM中，并能够影响人PSC衍生的发育性胎儿中胚层前体细胞（P-中胚层）的组织特异性分化。脱细胞ECM（dECM）由人心脏、肾脏和肺组织产生，并在不含任何分化诱导成分的培养基中与P-中胚层细胞重新细胞化。虽然肾脏dECM上的P-中胚层细胞仅分化为肾单位细胞，但心脏dECM上仅形成含有成熟和未成熟心肌细胞的跳动簇。在内胚层衍生的肺dECM上未观察到P-中胚层细胞的组织特异性分化。然而，在所有dECM制剂上均发现了P-中胚层衍生的内皮细胞，与组织来源无关。从dECM中清除硫酸乙酰肝素蛋白聚糖（HSPG）可消除组织特异性分化的诱导。得出的结论是，成人组织来源的ECM上与HSPG结合的因子对于诱导未分化胎儿期前体细胞的组织特异性特化是必不可少且足够的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665c/7055561/b1ee402d14b5/ADVS-7-1901198-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665c/7055561/dc595ff03e7d/ADVS-7-1901198-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665c/7055561/b1ee402d14b5/ADVS-7-1901198-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665c/7055561/dc595ff03e7d/ADVS-7-1901198-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665c/7055561/827b7a61c713/ADVS-7-1901198-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665c/7055561/53605af5d8b1/ADVS-7-1901198-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665c/7055561/c570de9eb80d/ADVS-7-1901198-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/665c/7055561/b1ee402d14b5/ADVS-7-1901198-g006.jpg

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