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
复制标题
自组装肽水凝胶3D培养系统中小鼠多能干细胞生成造血细胞
DOI：
10.1002/jcp.29110
复制
发表时间：
2019-08-06
影响因子：
5.6
通讯作者：
Huang，He
中科院分区：
文献类型：
--
作者：
Shan，Wei;Wang，Binsheng;Huang，He
从多能干细胞(PSCs)体外培养造血干细胞可作为替代骨髓移植的一种新的治疗方法，无免疫排斥反应或移植物抗宿主病。到目前为止，人们已经评价了许多不同的方法来引导PSCs向不同的造血细胞类型分化，然而，低效率和无功能限制了进一步的造血细胞分化研究，本研究旨在开发一种三维(3D)造血细胞分化方法，以重现胚胎体外发育的复杂程度，这是二维培养系统所不能达到的。我们首次发现，c-kit、CD41、CD45等造血细胞标志物在自组装多肽水凝胶中的表达可以有效地诱导小鼠PSCs向造血细胞分化。集落形成细胞实验结果表明，小鼠骨髓间充质干细胞(MPSCs)可分化为多潜能祖细胞，3D诱导系统来源的造血祖细胞具有向淋巴细胞分化的潜能。体内动物移植实验表明，移植3周后，mPSCs(CD45.2)可植入非肥胖型糖尿病/严重联合免疫缺陷小鼠(CD45.1)体内，植入率约为3%。本研究表明，我们建立的三维诱导方法能有效地促进骨髓间充质干细胞在体外的造血分化，并获得了具有短期植入潜能的多潜能祖细胞。
In vitro generation of hematopoietic stem cells from pluripotent stem cells (PSCs) can be regarded as novel therapeutic approaches for replacing bone marrow transplantation without immune rejection or graft versus host disease. To date, many different 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 aims to develop a three dimension (3D) hematopoietic differentiation approach that serves as recapitulation of embryonic development in vitro to a degree of complexity not achievable in a two dimension culture system. We first found that mouse PSCs could be efficiently induced to hematopoietic differentiation with an expression of hematopoietic makers, such as c‐kit, CD41, and CD45 within self‐assembling peptide hydrogel. Colony‐forming cells assay results suggested mouse PSCs (mPSCs) could be 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 be embedded into nonobese diabetic/severe combined immunodeficiency 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 promote the hematopoietic differentiation of mPSCs in vitro and obtained the multipotential progenitors that possessed the short‐term engraftment potential.