Generation of hematopoietic cells from mouse pluripotent stem cells in a 3D culture system of self-assembling peptide hydrogel.
Generation of hematopoietic cells from mouse pluripotent stem cells in a 3D culture system of self-assembling peptide hydrogel.
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在自组装肽水凝胶 3D 培养系统中从小鼠多能干细胞生成造血细胞。
DOI：
10.1002/jcp.26509
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发表时间：
2018-01
影响因子：
5.6
通讯作者：
He Huang
中科院分区：
文献类型：
--
作者：
Wei Shan;Weiyan Zheng;He Huang
多能干细胞（pluripotent stem cells，PSC）体外诱导造血干细胞（HSCs）是一种替代骨髓移植而不产生免疫排斥反应或移植物抗宿主病（graft versus host disease，GVHD）的新的治疗方法。迄今为止，许多分化方法已经在将PSC导向不同造血细胞类型方面进行了评估，然而，低效率和无功能限制了进一步的造血分化研究，我们的研究目的是开发一种三维（3D）造血分化方法，该方法可以再现胚胎体外发育的复杂程度，这在二维（2D）中是无法实现的。培养体系我们首次发现小鼠PSC在自组装肽水凝胶中可以有效地诱导向造血细胞分化，并表达c-kit、CD 41和CD 45等造血标志物。集落形成细胞检测结果表明mPSC可分化为多能祖细胞，3D诱导系统来源的造血集落具有向淋巴细胞分化的潜能。此外，体内动物移植实验表明，mPSC（CD45.2）可在NOD/SCID小鼠（CD45.1）体内包埋，移植3周后的植入率约为3%。本研究建立了一种三维诱导方法，可以有效地促进mPSCs的体外造血分化，获得具有短期植入潜能的多能祖细胞。本文受版权保护。All rights reserved.
In vitro generation of HSCs from pluripotent stem cells (PSCs) can be regarded as novel therapeutic approaches for replacing bone marrow (BM) transplantation without immune rejection or graft versus host disease(GVHD). To date, many differentiation approaches have been evaluated in terms of directing PSCs toward different hematopoietic cell types, yet, low efficiency and no function restrict the further hematopoietic differentiation study, our research aim to develop a three dimention (3D) hematopoietic differentiation approach that serve as recapitulation of embryonic development in vitro to a degree of complexity not achievable in a two dimention (2D) culture system. We first found that mouse PSCs could be efficiently induced to hematopoietic differentiation with expression of hematopoietic makers such as c-kit, CD41 and CD45 within self-assembling peptide hydrogel. Colony-forming cells assay results suggested mPSCs could differentiated into multipotential progenitor cells and 3D induction system derived hematopoietic colonies owned potential of differentiating into lymphocyte cells. In addition, in vivo animal transplantation experiment showed that mPSCs(CD45.2) could embedded into NOD/SCID mice(CD45.1) with about 3% engraftment efficiency after 3 weeks transplantation. This study demonstrated that we developed the 3D induction approach that could efficiently promoted the hematopoietic differentiation of mPSCs in vitro and obtained the multipotential progenitors that possessed the short-term engraftment potential. This article is protected by copyright. All rights reserved.
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