一种合成三维微环境系统有助于从人诱导多能干细胞生成功能性造血细胞。
A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells.
作者信息
Xu Yulin, Shan Wei, Li Xia, Wang Binsheng, Liu Senquan, Wang Yebo, Long Yan, Tie Ruxiu, Wang Limengmeng, Cai Shuyang, Zhang Hao, Lin Yu, Zhang Mingming, Zheng Weiyan, Luo Yi, Yu Xiaohong, Yee Jiing-Kuan, Ji Junfeng, Huang He
机构信息
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310012, China.
Department of Diabetes and Metabolic Diseases Research, City of Hope, Duarte, CA, 91010, USA.
出版信息
J Hematol Oncol. 2016 Sep 29;9(1):102. doi: 10.1186/s13045-016-0326-6.
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.
背景
从人诱导多能干细胞（iPSC）高效生成造血干细胞（HSC）在个性化移植治疗中具有巨大潜力。然而，迄今为止，从iPSC中获得功能性且可移植的HSC的成功率非常有限。
方法
我们开发了一种合成三维造血微环境系统，该系统由接种有骨髓（BM）来源的基质细胞和生长因子的纳米纤维组成，用于在体外诱导人iPSC生成功能性造血细胞。
结果
大约70%的人CD34造血细胞以及CD43祖细胞可从这个三维诱导系统中获得。集落形成单位（CFU）分析表明，iPSC来源的CD34细胞形成了包括CFU-GEMM在内的所有类型的造血集落。在分化过程中表达了与造血发育相关的关键转录因子TAL-1和MIXL1。此外，iPSC来源的造血细胞在移植后在受体NOD/SCID小鼠中产生了淋巴系和髓系谱系。
结论
我们的研究强调了合成三维微环境系统对于在体外从人iPSC中获得可移植造血细胞的重要性，从而为在临床上利用人iPSC来源的HSC进行移植治疗奠定了基础。
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