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

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 spec...

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Published inAdvanced science Vol. 7; no. 5; pp. 1901198 - n/a
Main Authors Ullah, Imran, Busch, Jonas Felix, Rabien, Anja, Ergün, Bettina, Stamm, Christof, Knosalla, Christoph, Hippenstiel, Stefan, Reinke, Petra, Kurtz, Andreas
Format Journal Article
LanguageEnglish
Published Germany John Wiley & Sons, Inc 01.03.2020
John Wiley and Sons Inc
Wiley
Subjects
cell differentiation
Extracellular matrix
Heart
Heparan sulfate
Morphogenesis
pluripotent stem cells
regenerative medicine
Stem cells
tissue engineering
Variables
cell differentiation
tissue engineering
pluripotent stem cells
regenerative medicine
extracellular matrix
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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. The extracellular matrix holds tissue‐specific memory, which can trigger efficient tissue‐specific differentiation of lineage committed cells. Cues responsible for the specification are conserved throughout development and depend on the presence of heparan sulfate proteoglycans (HSPGs). Modulation of HSPG‐decorating factors can be utilized for matrix engineering.
AbstractList 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.
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.
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. The extracellular matrix holds tissue‐specific memory, which can trigger efficient tissue‐specific differentiation of lineage committed cells. Cues responsible for the specification are conserved throughout development and depend on the presence of heparan sulfate proteoglycans (HSPGs). Modulation of HSPG‐decorating factors can be utilized for matrix engineering.
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.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.
Author Ergün, Bettina
Reinke, Petra
Hippenstiel, Stefan
Ullah, Imran
Kurtz, Andreas
Busch, Jonas Felix
Rabien, Anja
Stamm, Christof
Knosalla, Christoph
AuthorAffiliation 3 Berlin Institute for Urologic Research 10117 Berlin Germany
4 Deutsches Herzzentrum Berlin and German Center for Cardiovascular Research Augustenburger Platz 1 13353 Berlin Germany
1 Berlin Institute of Health Center for Regenerative Therapies Charité Universitätsmedizin Berlin Augustenburger Platz 1 13353 Berlin Germany
2 Department of Urology Charité–Universitätsmedizin Berlin 10117 Berlin Germany
5 Department of Infectiology and Pneumonology Charité–Universitätsmedizin Berlin Augustenburger Platz 1 13353 Berlin Germany
AuthorAffiliation_xml – name: 3 Berlin Institute for Urologic Research 10117 Berlin Germany
– name: 4 Deutsches Herzzentrum Berlin and German Center for Cardiovascular Research Augustenburger Platz 1 13353 Berlin Germany
– name: 1 Berlin Institute of Health Center for Regenerative Therapies Charité Universitätsmedizin Berlin Augustenburger Platz 1 13353 Berlin Germany
– name: 2 Department of Urology Charité–Universitätsmedizin Berlin 10117 Berlin Germany
– name: 5 Department of Infectiology and Pneumonology Charité–Universitätsmedizin Berlin Augustenburger Platz 1 13353 Berlin Germany
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/32154066$$D View this record in MEDLINE/PubMed
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Issue 5
Keywords cell differentiation
tissue engineering
pluripotent stem cells
regenerative medicine
extracellular matrix
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Snippet 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,...
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,...
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...
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StartPage 1901198
SubjectTerms cell differentiation
Extracellular matrix
Heart
Heparan sulfate
Morphogenesis
pluripotent stem cells
regenerative medicine
Stem cells
tissue engineering
Variables
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Title Adult Tissue Extracellular Matrix Determines Tissue Specification of Human iPSC‐Derived Embryonic Stage Mesodermal Precursor Cells
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fadvs.201901198
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