A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells

被引:14
作者
Xu, Yulin [1 ]
Shan, Wei [1 ]
Li, Xia [1 ]
Wang, Binsheng [1 ]
Liu, Senquan [1 ]
Wang, Yebo [1 ]
Long, Yan [1 ]
Tie, Ruxiu [1 ]
Wang, Limengmeng [1 ]
Cai, Shuyang [1 ]
Zhang, Hao [1 ]
Lin, Yu [1 ]
Zhang, Mingming [1 ]
Zheng, Weiyan [1 ]
Luo, Yi [1 ]
Yu, Xiaohong [1 ]
Yee, Jiing-Kuan [2 ]
Ji, Junfeng [3 ]
Huang, He [1 ]
机构
[1] Zhejiang Univ, Sch Med, Bone Marrow Transplantat Ctr, Affiliated Hosp 1, Hangzhou 310012, Zhejiang, Peoples R China
[2] City Hope Natl Med Ctr, Dept Diabet & Metab Dis Res, Duarte, CA 91010 USA
[3] Zhejiang Univ, Sch Med, Ctr Stem Cell & Regenerat Med, Hangzhou 310012, Zhejiang, Peoples R China
关键词
Induced pluripotent stem cells; Hematopoietic stem cells; Niche; Three dimension; Transplantation; PROGENITOR CELLS; STROMAL CELLS; DIFFERENTIATION; MOUSE; SPECIFICATION; TRANSPLANTATION; FIBROBLASTS; TECHNOLOGY; COMMITMENT; INDUCTION;
D O I
10.1186/s13045-016-0326-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
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页码:1 / 16
页数:16
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