Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steadystate blood using a polypeptide-forming 3D culture

doi:10.1007/s13238-021-00900-4

Protein & Cell

2022, Vol. 13

Issue (11): 808-824 https://doi.org/10.1007/s13238-021-00900-4

本期目录

Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steadystate blood using a polypeptide-forming 3D culture

Yulin Xu^1,^2,^3,⁴(

), Xiangjun Zeng^1,^2,^3,⁴, Mingming Zhang^1,^2,^3,⁴, Binsheng Wang^1,^2,^3,⁴, Xin Guo^1,^2,^3,⁴, Wei Shan^1,^2,^3,⁴, Shuyang Cai^1,^2,^3,⁴, Qian Luo^1,^2,^3,⁴, Honghu Li^1,^2,^3,⁴, Xia Li^1,^2,^3,⁴, Xue Li^1,^2,^3,⁴, Hao Zhang^1,^2,^3,⁴, Limengmeng Wang^1,^2,^3,⁴, Yu Lin^1,^2,^3,⁴, Lizhen Liu¹, Yanwei Li⁵, Meng Zhang^1,^2,^3,⁴, Xiaohong Yu^2,^3,⁴, Pengxu Qian^1,^2,^3,^4,⁶(

), He Huang^1,^2,^3,⁴(

)

¹. Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310012, China
². Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311121, China
³. Institute of Hematology, Zhejiang University, Hangzhou 310012, China
⁴. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310012, China
⁵. Core Facilities, Zhejiang University School of Medicine, Hangzhou 310012, China
⁶. Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310012, China

全文: PDF(6993 KB)

Abstract：

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.

Key words： hematopoietic stem/progenitor cell transplantation peripheral blood mononuclear cells expansion mobilization three-dimensional culture selfrenewal and multilineage differentiation

收稿日期: 2021-09-13 出版日期: 2022-11-10

Corresponding Author(s): Yulin Xu,Pengxu Qian,He Huang

引用本文:

. [J]. Protein & Cell, 2022, 13(11): 808-824.
Yulin Xu, Xiangjun Zeng, Mingming Zhang, Binsheng Wang, Xin Guo, Wei Shan, Shuyang Cai, Qian Luo, Honghu Li, Xia Li, Xue Li, Hao Zhang, Limengmeng Wang, Yu Lin, Lizhen Liu, Yanwei Li, Meng Zhang, Xiaohong Yu, Pengxu Qian, He Huang. Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steadystate blood using a polypeptide-forming 3D culture. Protein Cell, 2022, 13(11): 808-824.

链接本文:

https://academic.hep.com.cn/pac/CN/10.1007/s13238-021-00900-4
https://academic.hep.com.cn/pac/CN/Y2022/V13/I11/808

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