A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells.
A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells.
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合成的三维生态位系统有助于从人类诱导的多能干细胞生成功能性造血细胞
DOI：
10.1186/s13045-016-0326-6
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发表时间：
2016-09-29
影响因子：
28.5
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Xu Y;Shan W;Li X;Wang B;Liu S;Wang Y;Long Y;Tie R;Wang L;Cai S;Zhang H;Lin Y;Zhang M;Zheng W;Luo Y;Yu X;Yee JK;Ji J;Huang H
背景从人诱导多能干细胞 (iPSC) 中高效生成造血干细胞 (HSC) 在个性化移植治疗中具有广阔的前景。然而，迄今为止，从 iPSC 衍生出功能性和可移植的 HSC 的成功非常有限。方法我们开发了一种合成的 3D 造血生态位系统，其中包含接种了骨髓 (BM) 来源的基质细胞和生长因子的纳米纤维，以在体外诱导人类 iPSC 产生功能性造血细胞。结果大约 70% 的人类 CD34+ 造血细胞伴随着CD43+祖细胞可以源自该3D诱导系统。集落形成单位（CFU）测定显示，iPSC 衍生的 CD34+ 细胞形成包括 CFU-GEMM 在内的所有类型的造血集落。TAL-1 和 MIXL1（与造血发育相关的关键转录因子）在分化过程中表达。此外，iPSC 衍生的造血细胞在移植后在受体 NOD/SCID 小鼠中产生淋巴和骨髓谱系。结论我们的研究强调了合成 3D 生态位系统对于在体外从人 iPSC 衍生可移植造血细胞的重要性，从而为在临床中利用人 iPSC 衍生的 HSC 进行移植治疗奠定了基础。
BackgroundThe 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.MethodsWe 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.ResultsApproximately 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-1andMIXL1, 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.ConclusionsOur 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.
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影响因子：
4.6
作者：
Pearson, Stella;Sroczynska, Patrycja;Kouskoff, Valerie
通讯作者：
Kouskoff, Valerie
纳米神经编织：用于大脑修复和轴突再生以及视力功能恢复的肽纳米纤维支架
DOI：
10.1073/pnas.0600559103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Ellis-Behnke, RG;Liang, YX;Schneider, GE
通讯作者：
Schneider, GE
影响因子：
3.7
作者：
Kumada Y;Zhang S
通讯作者：
Zhang S
影响因子：
20.3
作者：
Amabile, Giovanni;Welner, Robert S.;Tenen, Daniel G.
通讯作者：
Tenen, Daniel G.
影响因子：
8.8
作者：
Kennedy, Marion;Awong, Geneve;Keller, Gordon
通讯作者：
Keller, Gordon