A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells
Abstract Background The efficient generation of hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (iPSCs) holds great promise in personalized transplantation therapies. However, the derivation of functional and transplantable HSCs from iPSCs has had very limited success thus...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2016-09-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-016-0326-6 |
| _version_ | 1818908929400242176 |
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| author | Yulin Xu Wei Shan Xia Li Binsheng Wang Senquan Liu Yebo Wang Yan Long Ruxiu Tie Limengmeng Wang Shuyang Cai Hao Zhang Yu Lin Mingming Zhang Weiyan Zheng Yi Luo Xiaohong Yu Jiing-Kuan Yee Junfeng Ji He Huang |
| author_facet | Yulin Xu Wei Shan Xia Li Binsheng Wang Senquan Liu Yebo Wang Yan Long Ruxiu Tie Limengmeng Wang Shuyang Cai Hao Zhang Yu Lin Mingming Zhang Weiyan Zheng Yi Luo Xiaohong Yu Jiing-Kuan Yee Junfeng Ji He Huang |
| author_sort | Yulin Xu |
| collection | DOAJ |
| description | Abstract Background The efficient generation of hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (iPSCs) holds great promise in personalized transplantation therapies. However, the derivation of functional and transplantable HSCs from iPSCs has had very limited success thus far. Methods We developed a synthetic 3D hematopoietic niche system comprising nanofibers seeded with bone marrow (BM)-derived stromal cells and growth factors to induce functional hematopoietic cells from human iPSCs in vitro. Results Approximately 70 % of human CD34+ hematopoietic cells accompanied with CD43+ progenitor cells could be derived from this 3D induction system. Colony-forming-unit (CFU) assay showed that iPSC-derived CD34+ cells formed all types of hematopoietic colonies including CFU-GEMM. TAL-1 and MIXL1, critical transcription factors associated with hematopoietic development, were expressed during the differentiation process. Furthermore, iPSC-derived hematopoietic cells gave rise to both lymphoid and myeloid lineages in the recipient NOD/SCID mice after transplantation. Conclusions Our study underscores the importance of a synthetic 3D niche system for the derivation of transplantable hematopoietic cells from human iPSCs in vitro thereby establishing a foundation towards utilization of human iPSC-derived HSCs for transplantation therapies in the clinic. |
| first_indexed | 2024-12-19T22:18:49Z |
| format | Article |
| id | doaj.art-5c7d3ea880b6494b839e829347ed5584 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-19T22:18:49Z |
| publishDate | 2016-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-5c7d3ea880b6494b839e829347ed55842022-12-21T20:03:41ZengBMCJournal of Hematology & Oncology1756-87222016-09-019111610.1186/s13045-016-0326-6A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cellsYulin Xu0Wei Shan1Xia Li2Binsheng Wang3Senquan Liu4Yebo Wang5Yan Long6Ruxiu Tie7Limengmeng Wang8Shuyang Cai9Hao Zhang10Yu Lin11Mingming Zhang12Weiyan Zheng13Yi Luo14Xiaohong Yu15Jiing-Kuan Yee16Junfeng Ji17He Huang18Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Diabetes and Metabolic Diseases Research, City of HopeCenter of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang UniversityBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityAbstract Background The efficient generation of hematopoietic stem cells (HSCs) from human-induced pluripotent stem cells (iPSCs) holds great promise in personalized transplantation therapies. However, the derivation of functional and transplantable HSCs from iPSCs has had very limited success thus far. Methods We developed a synthetic 3D hematopoietic niche system comprising nanofibers seeded with bone marrow (BM)-derived stromal cells and growth factors to induce functional hematopoietic cells from human iPSCs in vitro. Results Approximately 70 % of human CD34+ hematopoietic cells accompanied with CD43+ progenitor cells could be derived from this 3D induction system. Colony-forming-unit (CFU) assay showed that iPSC-derived CD34+ cells formed all types of hematopoietic colonies including CFU-GEMM. TAL-1 and MIXL1, critical transcription factors associated with hematopoietic development, were expressed during the differentiation process. Furthermore, iPSC-derived hematopoietic cells gave rise to both lymphoid and myeloid lineages in the recipient NOD/SCID mice after transplantation. Conclusions Our study underscores the importance of a synthetic 3D niche system for the derivation of transplantable hematopoietic cells from human iPSCs in vitro thereby establishing a foundation towards utilization of human iPSC-derived HSCs for transplantation therapies in the clinic.http://link.springer.com/article/10.1186/s13045-016-0326-6Induced pluripotent stem cellsHematopoietic stem cellsNicheThree dimensionTransplantation |
| spellingShingle | Yulin Xu Wei Shan Xia Li Binsheng Wang Senquan Liu Yebo Wang Yan Long Ruxiu Tie Limengmeng Wang Shuyang Cai Hao Zhang Yu Lin Mingming Zhang Weiyan Zheng Yi Luo Xiaohong Yu Jiing-Kuan Yee Junfeng Ji He Huang A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells Journal of Hematology & Oncology Induced pluripotent stem cells Hematopoietic stem cells Niche Three dimension Transplantation |
| title | A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells |
| title_full | A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells |
| title_fullStr | A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells |
| title_full_unstemmed | A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells |
| title_short | A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells |
| title_sort | synthetic three dimensional niche system facilitates generation of functional hematopoietic cells from human induced pluripotent stem cells |
| topic | Induced pluripotent stem cells Hematopoietic stem cells Niche Three dimension Transplantation |
| url | http://link.springer.com/article/10.1186/s13045-016-0326-6 |
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