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Human ESC-derived Neuromesodermal Progenitors (NMPs) Successfully Differentiate into Mesenchymal Stem Cells (MSCs)
Mesenchymal Stem Cells (MSCs), as an adult stem cell type, are used to treat various disorders in clinics. However, derivation of homogenous and adequate amount of MSCs limits the regenerative treatment potential. Although mesoderm is the main source of mesenchymal progenitors during embryonic devel...
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Published in: | Stem cell reviews and reports 2022, Vol.18 (1), p.278-293 |
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creator | Şenkal, Selinay Hayal, Taha Bartu Sağraç, Derya Şişli, Hatice Burcu Asutay, Ayla Burçin Kıratlı, Binnur Sümer, Engin Rizvanov, Albert A. Şahin, Fikrettin Doğan, Ayşegül |
description | Mesenchymal Stem Cells (MSCs), as an adult stem cell type, are used to treat various disorders in clinics. However, derivation of homogenous and adequate amount of MSCs limits the regenerative treatment potential. Although mesoderm is the main source of mesenchymal progenitors during embryonic development, neuromesodermal progenitors (NMPs), reside in the primitive streak during development, is known to differentiate into paraxial mesoderm. In the current study, we generated NMPs from human embryonic stem cells (hESC), subsequently derived MSCs and characterized this cell population
in vitro
and
in vivo
. Using a bFGF and CHIR induced NMP formation protocol followed by serum containing culture conditions; here we show that MSCs can be generated from NMPs identified by not only the expression of T/Bra and Sox 2 but also FLK-1/PDGFRα in our study. NMP-derived MSCs were plastic adherent fibroblast like cells with colony forming capacity and trilineage (osteo-, chondro- and adipo-genic) differentiation potential. In the present study, we demonstrate that NMP-derived MSCs have an endothelial tendency which might be related to their FLK-1+/PDGFRα + NMP origin. NMP-derived MSCs displayed a protein expression profile of characterized MSCs. Growth factor and angiogenesis related pathway proteins were similarly expressed in NMP-derived MSCs and characterized MSCs. NMP-derived MSCs keep characteristics after short-term and long-term freeze-thaw cycles and localized into bone marrow followed by tail vein injection into NOD/SCID mice. Together, these data showed that hESC-derived NMPs might be used as a precursor cell population for MSC derivation and could be used for
in vitro
and
in vivo
research.
Graphical abstract |
doi_str_mv | 10.1007/s12015-021-10281-0 |
format | article |
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in vitro
and
in vivo
. Using a bFGF and CHIR induced NMP formation protocol followed by serum containing culture conditions; here we show that MSCs can be generated from NMPs identified by not only the expression of T/Bra and Sox 2 but also FLK-1/PDGFRα in our study. NMP-derived MSCs were plastic adherent fibroblast like cells with colony forming capacity and trilineage (osteo-, chondro- and adipo-genic) differentiation potential. In the present study, we demonstrate that NMP-derived MSCs have an endothelial tendency which might be related to their FLK-1+/PDGFRα + NMP origin. NMP-derived MSCs displayed a protein expression profile of characterized MSCs. Growth factor and angiogenesis related pathway proteins were similarly expressed in NMP-derived MSCs and characterized MSCs. NMP-derived MSCs keep characteristics after short-term and long-term freeze-thaw cycles and localized into bone marrow followed by tail vein injection into NOD/SCID mice. Together, these data showed that hESC-derived NMPs might be used as a precursor cell population for MSC derivation and could be used for
in vitro
and
in vivo
research.
Graphical abstract</description><identifier>ISSN: 2629-3269</identifier><identifier>EISSN: 2629-3277</identifier><identifier>DOI: 10.1007/s12015-021-10281-0</identifier><identifier>PMID: 34669151</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Angiogenesis ; Animals ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Bone marrow ; Cell Biology ; Cell culture ; Cell differentiation ; Embryo cells ; Embryogenesis ; Female ; Fibroblast growth factor 2 ; Freeze-thawing ; Humans ; Life Sciences ; Mesenchymal Stem Cells ; Mesoderm ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Pregnancy ; Primitive streak ; Progenitor cells ; Receptor, Platelet-Derived Growth Factor alpha - genetics ; Receptor, Platelet-Derived Growth Factor alpha - metabolism ; Regenerative Medicine/Tissue Engineering ; Stem cell transplantation ; Stem Cells ; Vascular endothelial growth factor receptor 2</subject><ispartof>Stem cell reviews and reports, 2022, Vol.18 (1), p.278-293</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-6bb95047f929a6060e2788ff14417373f887b527e9cdbd9e97d82b4bf1c191fe3</citedby><cites>FETCH-LOGICAL-c375t-6bb95047f929a6060e2788ff14417373f887b527e9cdbd9e97d82b4bf1c191fe3</cites><orcidid>0000-0003-4160-2270</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34669151$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Şenkal, Selinay</creatorcontrib><creatorcontrib>Hayal, Taha Bartu</creatorcontrib><creatorcontrib>Sağraç, Derya</creatorcontrib><creatorcontrib>Şişli, Hatice Burcu</creatorcontrib><creatorcontrib>Asutay, Ayla Burçin</creatorcontrib><creatorcontrib>Kıratlı, Binnur</creatorcontrib><creatorcontrib>Sümer, Engin</creatorcontrib><creatorcontrib>Rizvanov, Albert A.</creatorcontrib><creatorcontrib>Şahin, Fikrettin</creatorcontrib><creatorcontrib>Doğan, Ayşegül</creatorcontrib><title>Human ESC-derived Neuromesodermal Progenitors (NMPs) Successfully Differentiate into Mesenchymal Stem Cells (MSCs)</title><title>Stem cell reviews and reports</title><addtitle>Stem Cell Rev and Rep</addtitle><addtitle>Stem Cell Rev Rep</addtitle><description>Mesenchymal Stem Cells (MSCs), as an adult stem cell type, are used to treat various disorders in clinics. However, derivation of homogenous and adequate amount of MSCs limits the regenerative treatment potential. Although mesoderm is the main source of mesenchymal progenitors during embryonic development, neuromesodermal progenitors (NMPs), reside in the primitive streak during development, is known to differentiate into paraxial mesoderm. In the current study, we generated NMPs from human embryonic stem cells (hESC), subsequently derived MSCs and characterized this cell population
in vitro
and
in vivo
. Using a bFGF and CHIR induced NMP formation protocol followed by serum containing culture conditions; here we show that MSCs can be generated from NMPs identified by not only the expression of T/Bra and Sox 2 but also FLK-1/PDGFRα in our study. NMP-derived MSCs were plastic adherent fibroblast like cells with colony forming capacity and trilineage (osteo-, chondro- and adipo-genic) differentiation potential. In the present study, we demonstrate that NMP-derived MSCs have an endothelial tendency which might be related to their FLK-1+/PDGFRα + NMP origin. NMP-derived MSCs displayed a protein expression profile of characterized MSCs. Growth factor and angiogenesis related pathway proteins were similarly expressed in NMP-derived MSCs and characterized MSCs. NMP-derived MSCs keep characteristics after short-term and long-term freeze-thaw cycles and localized into bone marrow followed by tail vein injection into NOD/SCID mice. Together, these data showed that hESC-derived NMPs might be used as a precursor cell population for MSC derivation and could be used for
in vitro
and
in vivo
research.
Graphical abstract</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Bone marrow</subject><subject>Cell Biology</subject><subject>Cell culture</subject><subject>Cell differentiation</subject><subject>Embryo cells</subject><subject>Embryogenesis</subject><subject>Female</subject><subject>Fibroblast growth factor 2</subject><subject>Freeze-thawing</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Mesenchymal Stem Cells</subject><subject>Mesoderm</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Pregnancy</subject><subject>Primitive streak</subject><subject>Progenitor cells</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - genetics</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - metabolism</subject><subject>Regenerative Medicine/Tissue Engineering</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>Vascular endothelial growth factor receptor 2</subject><issn>2629-3269</issn><issn>2629-3277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u1TAQhS0EolXpC7BAlti0i8CMncTxEqWFVuotlS6srfyMS6okLp4E6b49bm8pEgtWY42_c2Y0R4i3CB8QwHxkVIBFBgozBFVhBi_EoSqVzbQy5uXzu7QH4pj5DgCUhjxpXosDnZelxQIPRbxYp2aW59s66ykOv6iX17TGMBGH1JiaUd7EcEvzsITI8uR6c8Oncrt2HTH7dRx38mzwniLNy9AsJId5CXJDTHP3Y_cg3y40yZrGMak325pP34hXvhmZjp_qkfj--fxbfZFdff1yWX-6yjptiiUr29YWkBtvlW1KKIGUqSrvMc_RaKN9VZm2UIZs17e9JWv6SrV567FDi570kTjZ-97H8HMlXtw0cJcWaWYKKztVVOkcubImoe__Qe_CGue0nUtn1AUg5Jgotae6GJgjeXcfh6mJO4fgHkJx-1BcCsU9huIgid49Wa_tRP2z5E8ECdB7gNPXfEvx7-z_2P4G8_iVzg</recordid><startdate>2022</startdate><enddate>2022</enddate><creator>Şenkal, Selinay</creator><creator>Hayal, Taha Bartu</creator><creator>Sağraç, Derya</creator><creator>Şişli, Hatice Burcu</creator><creator>Asutay, Ayla Burçin</creator><creator>Kıratlı, Binnur</creator><creator>Sümer, Engin</creator><creator>Rizvanov, Albert A.</creator><creator>Şahin, Fikrettin</creator><creator>Doğan, Ayşegül</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4160-2270</orcidid></search><sort><creationdate>2022</creationdate><title>Human ESC-derived Neuromesodermal Progenitors (NMPs) Successfully Differentiate into Mesenchymal Stem Cells (MSCs)</title><author>Şenkal, Selinay ; Hayal, Taha Bartu ; Sağraç, Derya ; Şişli, Hatice Burcu ; Asutay, Ayla Burçin ; Kıratlı, Binnur ; Sümer, Engin ; Rizvanov, Albert A. ; Şahin, Fikrettin ; Doğan, Ayşegül</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-6bb95047f929a6060e2788ff14417373f887b527e9cdbd9e97d82b4bf1c191fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Bone marrow</topic><topic>Cell Biology</topic><topic>Cell culture</topic><topic>Cell differentiation</topic><topic>Embryo cells</topic><topic>Embryogenesis</topic><topic>Female</topic><topic>Fibroblast growth factor 2</topic><topic>Freeze-thawing</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Mesenchymal Stem Cells</topic><topic>Mesoderm</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Pregnancy</topic><topic>Primitive streak</topic><topic>Progenitor cells</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - genetics</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - metabolism</topic><topic>Regenerative Medicine/Tissue Engineering</topic><topic>Stem cell transplantation</topic><topic>Stem Cells</topic><topic>Vascular endothelial growth factor receptor 2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Şenkal, Selinay</creatorcontrib><creatorcontrib>Hayal, Taha Bartu</creatorcontrib><creatorcontrib>Sağraç, Derya</creatorcontrib><creatorcontrib>Şişli, Hatice Burcu</creatorcontrib><creatorcontrib>Asutay, Ayla Burçin</creatorcontrib><creatorcontrib>Kıratlı, Binnur</creatorcontrib><creatorcontrib>Sümer, Engin</creatorcontrib><creatorcontrib>Rizvanov, Albert A.</creatorcontrib><creatorcontrib>Şahin, Fikrettin</creatorcontrib><creatorcontrib>Doğan, Ayşegül</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Stem cell reviews and reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Şenkal, Selinay</au><au>Hayal, Taha Bartu</au><au>Sağraç, Derya</au><au>Şişli, Hatice Burcu</au><au>Asutay, Ayla Burçin</au><au>Kıratlı, Binnur</au><au>Sümer, Engin</au><au>Rizvanov, Albert A.</au><au>Şahin, Fikrettin</au><au>Doğan, Ayşegül</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human ESC-derived Neuromesodermal Progenitors (NMPs) Successfully Differentiate into Mesenchymal Stem Cells (MSCs)</atitle><jtitle>Stem cell reviews and reports</jtitle><stitle>Stem Cell Rev and Rep</stitle><addtitle>Stem Cell Rev Rep</addtitle><date>2022</date><risdate>2022</risdate><volume>18</volume><issue>1</issue><spage>278</spage><epage>293</epage><pages>278-293</pages><issn>2629-3269</issn><eissn>2629-3277</eissn><abstract>Mesenchymal Stem Cells (MSCs), as an adult stem cell type, are used to treat various disorders in clinics. However, derivation of homogenous and adequate amount of MSCs limits the regenerative treatment potential. Although mesoderm is the main source of mesenchymal progenitors during embryonic development, neuromesodermal progenitors (NMPs), reside in the primitive streak during development, is known to differentiate into paraxial mesoderm. In the current study, we generated NMPs from human embryonic stem cells (hESC), subsequently derived MSCs and characterized this cell population
in vitro
and
in vivo
. Using a bFGF and CHIR induced NMP formation protocol followed by serum containing culture conditions; here we show that MSCs can be generated from NMPs identified by not only the expression of T/Bra and Sox 2 but also FLK-1/PDGFRα in our study. NMP-derived MSCs were plastic adherent fibroblast like cells with colony forming capacity and trilineage (osteo-, chondro- and adipo-genic) differentiation potential. In the present study, we demonstrate that NMP-derived MSCs have an endothelial tendency which might be related to their FLK-1+/PDGFRα + NMP origin. NMP-derived MSCs displayed a protein expression profile of characterized MSCs. Growth factor and angiogenesis related pathway proteins were similarly expressed in NMP-derived MSCs and characterized MSCs. NMP-derived MSCs keep characteristics after short-term and long-term freeze-thaw cycles and localized into bone marrow followed by tail vein injection into NOD/SCID mice. Together, these data showed that hESC-derived NMPs might be used as a precursor cell population for MSC derivation and could be used for
in vitro
and
in vivo
research.
Graphical abstract</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34669151</pmid><doi>10.1007/s12015-021-10281-0</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-4160-2270</orcidid></addata></record> |
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subjects | Angiogenesis Animals Biomedical and Life Sciences Biomedical Engineering and Bioengineering Bone marrow Cell Biology Cell culture Cell differentiation Embryo cells Embryogenesis Female Fibroblast growth factor 2 Freeze-thawing Humans Life Sciences Mesenchymal Stem Cells Mesoderm Mice Mice, Inbred NOD Mice, SCID Pregnancy Primitive streak Progenitor cells Receptor, Platelet-Derived Growth Factor alpha - genetics Receptor, Platelet-Derived Growth Factor alpha - metabolism Regenerative Medicine/Tissue Engineering Stem cell transplantation Stem Cells Vascular endothelial growth factor receptor 2 |
title | Human ESC-derived Neuromesodermal Progenitors (NMPs) Successfully Differentiate into Mesenchymal Stem Cells (MSCs) |
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