Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells
Here we report the successful generation and long-term expansion of SOX9-expressing CD271+PDGFRα+CD73+ chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1−CD271hiPDGFRαloCD73− neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemen...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-04-01
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| Series: | Stem Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671115000685 |
| _version_ | 1817971107121070080 |
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| author | Katsutsugu Umeda Hirotsugu Oda Qing Yan Nadine Matthias Jiangang Zhao Brian R. Davis Naoki Nakayama |
| author_facet | Katsutsugu Umeda Hirotsugu Oda Qing Yan Nadine Matthias Jiangang Zhao Brian R. Davis Naoki Nakayama |
| author_sort | Katsutsugu Umeda |
| collection | DOAJ |
| description | Here we report the successful generation and long-term expansion of SOX9-expressing CD271+PDGFRα+CD73+ chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1−CD271hiPDGFRαloCD73− neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemented with Nodal/Activin/transforming growth factorβ (TGFβ) inhibitor and fibroblast growth factor (FGF). When “primed” with TGFβ, such cells efficiently formed translucent cartilage particles, which were completely mineralized in 12 weeks in immunocompromized mice. The ectomesenchymal cells were expandable without loss of chondrogenic potential for at least 16 passages. They maintained normal karyotype for at least 10 passages and expressed genes representing embryonic progenitors (SOX4/12, LIN28A/B), cranial mesenchyme (ALX1/3/4), and chondroprogenitors (SOX9, COL2A1) of neural crest origin (SOX8/9, NGFR, NES). Ectomesenchyme is a source of many craniofacial bone and cartilage structures. The method we describe for obtaining a large quantity of human ectomesenchymal cells will help to model craniofacial disorders in vitro and potentially provide cells for the repair of craniofacial damage. |
| first_indexed | 2024-04-13T20:42:26Z |
| format | Article |
| id | doaj.art-7a68c48ec3a1400d8b03d78eb8d80020 |
| institution | Directory Open Access Journal |
| issn | 2213-6711 |
| language | English |
| last_indexed | 2024-04-13T20:42:26Z |
| publishDate | 2015-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Reports |
| spelling | doaj.art-7a68c48ec3a1400d8b03d78eb8d800202022-12-22T02:30:48ZengElsevierStem Cell Reports2213-67112015-04-014471272610.1016/j.stemcr.2015.02.012Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem CellsKatsutsugu Umeda0Hirotsugu Oda1Qing Yan2Nadine Matthias3Jiangang Zhao4Brian R. Davis5Naoki Nakayama6Institute of Molecular Medicine, The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USADepartment of Pediatrics, Kyoto University School of Medicine, Kyoto 606-8507, JapanInstitute of Molecular Medicine, The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USAInstitute of Molecular Medicine, The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USAInstitute of Molecular Medicine, The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USAInstitute of Molecular Medicine, The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USAInstitute of Molecular Medicine, The University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, USAHere we report the successful generation and long-term expansion of SOX9-expressing CD271+PDGFRα+CD73+ chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1−CD271hiPDGFRαloCD73− neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemented with Nodal/Activin/transforming growth factorβ (TGFβ) inhibitor and fibroblast growth factor (FGF). When “primed” with TGFβ, such cells efficiently formed translucent cartilage particles, which were completely mineralized in 12 weeks in immunocompromized mice. The ectomesenchymal cells were expandable without loss of chondrogenic potential for at least 16 passages. They maintained normal karyotype for at least 10 passages and expressed genes representing embryonic progenitors (SOX4/12, LIN28A/B), cranial mesenchyme (ALX1/3/4), and chondroprogenitors (SOX9, COL2A1) of neural crest origin (SOX8/9, NGFR, NES). Ectomesenchyme is a source of many craniofacial bone and cartilage structures. The method we describe for obtaining a large quantity of human ectomesenchymal cells will help to model craniofacial disorders in vitro and potentially provide cells for the repair of craniofacial damage.http://www.sciencedirect.com/science/article/pii/S2213671115000685 |
| spellingShingle | Katsutsugu Umeda Hirotsugu Oda Qing Yan Nadine Matthias Jiangang Zhao Brian R. Davis Naoki Nakayama Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells Stem Cell Reports |
| title | Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells |
| title_full | Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells |
| title_fullStr | Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells |
| title_full_unstemmed | Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells |
| title_short | Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells |
| title_sort | long term expandable sox9 chondrogenic ectomesenchymal cells from human pluripotent stem cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213671115000685 |
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