Human induced pluripotent stem cell-derived endothelial cells exhibit functional heterogeneity
Identifieur interne : 005602 ( Ncbi/Merge ); précédent : 005601; suivant : 005603Human induced pluripotent stem cell-derived endothelial cells exhibit functional heterogeneity
Auteurs : Abdul Jalil Rufaihah [États-Unis] ; Ngan F. Huang [États-Unis] ; Jeanna Kim [États-Unis] ; Joerg Herold [États-Unis] ; Katharina S. Volz [États-Unis] ; Tea Soon Park [États-Unis] ; Jerry C. Lee [États-Unis] ; Elias T. Zambidis [États-Unis] ; Renee Reijo-Pera [États-Unis] ; John P. Cooke [États-Unis]Source :
- American Journal of Translational Research [ 1943-8141 ] ; 2013.
Abstract
Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) are promising for treatment of vascular diseases. However, hiPSC-ECs purified based on CD31 expression are comprised of arterial, venous, and lymphatic subtypes. It is unclear whether hiPSC-ECs are heterogeneous in nature, and whether there may be functional benefits of enriching for specific subtypes. Therefore, we sought to characterize the hiPSC-ECs and enrich for each subtype, and demonstrate whether such enrichment would have functional significance. The hiPSC-ECs were generated from differentiation of hiPSCs using vascular endothelial growth factor (VEGF)-A and bone morphogenetic protein-4. The hiPSC-ECs were purified based on positive expression of CD31. Subsequently, we sought to enrich for each subtype. Arterial hiPSC-ECs were induced using higher concentrations of VEGF-A and 8-bromoadenosine-3’:5’-cyclic monophosphate in the media, whereas lower concentrations of VEGF-A favored venous subtype. VEGF-C and angiopoietin-1 promoted the expression of lymphatic phenotype. Upon FACS purification based on CD31+ expression, the hiPSC-EC population was observed to display typical endothelial surface markers and functions. However, the hiPSC-EC population was heterogeneous in that they displayed arterial, venous, and to a lesser degree, lymphatic lineage markers. Upon comparing vascular formation in matrigel plugs
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PubMed: 23390563
PubMed Central: 3560482
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<front><div type="abstract" xml:lang="en"><p>Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) are promising for treatment of vascular diseases. However, hiPSC-ECs purified based on CD31 expression are comprised of arterial, venous, and lymphatic subtypes. It is unclear whether hiPSC-ECs are heterogeneous in nature, and whether there may be functional benefits of enriching for specific subtypes. Therefore, we sought to characterize the hiPSC-ECs and enrich for each subtype, and demonstrate whether such enrichment would have functional significance. The hiPSC-ECs were generated from differentiation of hiPSCs using vascular endothelial growth factor (VEGF)-A and bone morphogenetic protein-4. The hiPSC-ECs were purified based on positive expression of CD31. Subsequently, we sought to enrich for each subtype. Arterial hiPSC-ECs were induced using higher concentrations of VEGF-A and 8-bromoadenosine-3’:5’-cyclic monophosphate in the media, whereas lower concentrations of VEGF-A favored venous subtype. VEGF-C and angiopoietin-1 promoted the expression of lymphatic phenotype. Upon FACS purification based on CD31+ expression, the hiPSC-EC population was observed to display typical endothelial surface markers and functions. However, the hiPSC-EC population was heterogeneous in that they displayed arterial, venous, and to a lesser degree, lymphatic lineage markers. Upon comparing vascular formation in matrigel plugs <italic>in vivo</italic>
, we observed that arterial enriched hiPSC-ECs formed a more extensive capillary network in this model, by comparison to a heterogeneous population of hiPSC-ECs. This study demonstrates that FACS purification of CD31+ hiPSC-ECs produces a diverse population of ECs. Refining the differentiation methods can enrich for subtype-specific hiPSC-ECs with functional benefits of enhancing neovascularization.</p>
</div>
</front>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Transl Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Am J Transl Res</journal-id>
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<article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Human induced pluripotent stem cell-derived endothelial cells exhibit functional heterogeneity</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Rufaihah</surname>
<given-names>Abdul Jalil</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Huang</surname>
<given-names>Ngan F</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kim</surname>
<given-names>Jeanna</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Herold</surname>
<given-names>Joerg</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Volz</surname>
<given-names>Katharina S</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Park</surname>
<given-names>Tea Soon</given-names>
</name>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Jerry C</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zambidis</surname>
<given-names>Elias T</given-names>
</name>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Reijo-Pera</surname>
<given-names>Renee</given-names>
</name>
<xref ref-type="aff" rid="au3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cooke</surname>
<given-names>John P</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<aff id="au1"><label>1</label>
<institution>Division of Cardiovascular Medicine, Stanford University School of Medicine</institution>
<addr-line>300 Pasteur Drive, Stanford, CA 94305, USA</addr-line>
</aff>
<aff id="au2"><label>2</label>
<institution>Johns Hopkins Institute for Cell Engineering, The Johns Hopkins University School of Medicine</institution>
<addr-line>733 N. Broadway, BRB 755 Baltimore, MD, 21205, USA</addr-line>
</aff>
<aff id="au3"><label>3</label>
<institution>Institute for Stem Cell Biology & Regenerative Medicine, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University</institution>
<addr-line>300 Pasteur Drive, Stanford, CA 94305, USA</addr-line>
</aff>
</contrib-group>
<author-notes><corresp><bold>Address correspondence to:</bold>
Dr. John P Cooke, Division of Cardiovascular Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA. Fax: 650-7238392; Phone: 650-7236459; E-mail: <email>john.cooke@stanford.edu</email>
</corresp>
<fn id="fn1"><label>*</label>
<p>Contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>21</day>
<month>1</month>
<year>2013</year>
</pub-date>
<volume>5</volume>
<issue>1</issue>
<fpage>21</fpage>
<lpage>35</lpage>
<history><date date-type="received"><day>01</day>
<month>11</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>03</day>
<month>12</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>AJTR Copyright © 2013</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<abstract><p>Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) are promising for treatment of vascular diseases. However, hiPSC-ECs purified based on CD31 expression are comprised of arterial, venous, and lymphatic subtypes. It is unclear whether hiPSC-ECs are heterogeneous in nature, and whether there may be functional benefits of enriching for specific subtypes. Therefore, we sought to characterize the hiPSC-ECs and enrich for each subtype, and demonstrate whether such enrichment would have functional significance. The hiPSC-ECs were generated from differentiation of hiPSCs using vascular endothelial growth factor (VEGF)-A and bone morphogenetic protein-4. The hiPSC-ECs were purified based on positive expression of CD31. Subsequently, we sought to enrich for each subtype. Arterial hiPSC-ECs were induced using higher concentrations of VEGF-A and 8-bromoadenosine-3’:5’-cyclic monophosphate in the media, whereas lower concentrations of VEGF-A favored venous subtype. VEGF-C and angiopoietin-1 promoted the expression of lymphatic phenotype. Upon FACS purification based on CD31+ expression, the hiPSC-EC population was observed to display typical endothelial surface markers and functions. However, the hiPSC-EC population was heterogeneous in that they displayed arterial, venous, and to a lesser degree, lymphatic lineage markers. Upon comparing vascular formation in matrigel plugs <italic>in vivo</italic>
, we observed that arterial enriched hiPSC-ECs formed a more extensive capillary network in this model, by comparison to a heterogeneous population of hiPSC-ECs. This study demonstrates that FACS purification of CD31+ hiPSC-ECs produces a diverse population of ECs. Refining the differentiation methods can enrich for subtype-specific hiPSC-ECs with functional benefits of enhancing neovascularization.</p>
</abstract>
<kwd-group><kwd>Heterogeneity</kwd>
<kwd>induced pluripotent stem cells</kwd>
<kwd>differentiation</kwd>
<kwd>endothelial cells</kwd>
<kwd>angiogenesis</kwd>
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<name sortKey="Herold, Joerg" sort="Herold, Joerg" uniqKey="Herold J" first="Joerg" last="Herold">Joerg Herold</name>
<name sortKey="Huang, Ngan F" sort="Huang, Ngan F" uniqKey="Huang N" first="Ngan F" last="Huang">Ngan F. Huang</name>
<name sortKey="Kim, Jeanna" sort="Kim, Jeanna" uniqKey="Kim J" first="Jeanna" last="Kim">Jeanna Kim</name>
<name sortKey="Lee, Jerry C" sort="Lee, Jerry C" uniqKey="Lee J" first="Jerry C" last="Lee">Jerry C. Lee</name>
<name sortKey="Park, Tea Soon" sort="Park, Tea Soon" uniqKey="Park T" first="Tea Soon" last="Park">Tea Soon Park</name>
<name sortKey="Reijo Pera, Renee" sort="Reijo Pera, Renee" uniqKey="Reijo Pera R" first="Renee" last="Reijo-Pera">Renee Reijo-Pera</name>
<name sortKey="Volz, Katharina S" sort="Volz, Katharina S" uniqKey="Volz K" first="Katharina S" last="Volz">Katharina S. Volz</name>
<name sortKey="Zambidis, Elias T" sort="Zambidis, Elias T" uniqKey="Zambidis E" first="Elias T" last="Zambidis">Elias T. Zambidis</name>
</country>
</tree>
</affiliations>
</record>
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