Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steady-state blood using a polypeptide-forming 3D culture. Issue 11 (1st March 2022)

• Record Type: Journal Article
• Authors: Xu, Yulin; Zeng, Xiangjun; Zhang, Mingming; Wang, Binsheng; Guo, Xin; Shan, Wei; Cai, Shuyang; Luo, Qian; Li, Honghu; Li, Xia; Li, Xue; Zhang, Hao; Wang, Limengmeng; Lin, Yu; Liu, Lizhen; Li, Yanwei; Zhang, Meng; Yu, Xiaohong; Qian, Pengxu; Huang, He
• Is Part Of: Protein & cell. Volume 13:Issue 11(2022)
• Page Start: 808
• Page End: 824
• Publication Date: 2022-03-01
• Subjects: hematopoietic stem/progenitor cell transplantation -- peripheral blood mononuclear cells -- expansion -- mobilization -- three-dimensional culture -- self-renewal and multilineage differentiation; Proteins -- Periodicals; Cells -- Periodicals; Cytology -- Periodicals; 572.6
• DOI: 10.1007/s13238-021-00900-4
• Languages: English
• ISSNs: 1674-800X

Abstract

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.