| 摘要: |
Dingkun Peng, Meilin Li, Zhuoran Yu, Tingsheng Yan, Meng Yao, Su Li, Zhonghua Liu, Lian-Feng Li, Hua-Ji Qiu
Cell Prolif.2024 Nov 13:e13770.doi: 10.1111/cpr.13770. Online ahead of print.
Review
Abstract
As crucial phagocytes of the innate immune system, macrophages (M?s) protect mammalian hosts, maintain tissue homeostasis and influence disease pathogenesis. Nonetheless, M?s are susceptible to various pathogens, including bacteria, viruses and parasites, which cause various infectious diseases, necessitating a deeper understanding of pathogen-M? interactions and therapeutic insights. Pluripotent stem cells (PSCs) have been efficiently differentiated into PSC-derived M?s (PSCdM?s) resembling primary M?s, advancing the modelling and cell therapy of infectious diseases. However, the mass production of PSCdM?s, which lack proliferative capacity, relies on large-scale expansions of PSCs, thereby increasing both costs and culture cycles. Notably, M?s deficient in the MafB/c-Maf genes have been reported to re-enter the cell cycle with the stimulation of specific growth factor cocktails, turning into self-renewing M?s (SRM?s). This review summarizes the applications of PSCdM?s in the modelling and cell therapy of infectious diseases and strategies for establishing SRM?s. Most importantly, we innovatively propose that PSCs can serve as a gene editing platform to creating PSC-derived SRM?s (termed PSRM?s), addressing the resistance of M?s against genetic manipulation. We discuss the challenges and possible solutions in creating PSRM?s. In conclusion, this review provides novel insights into the development of physiologically relevant and expandable M? models, highlighting the enormous potential of PSRM?s as a promising avenue for the modelling and cell therapy of infectious diseases.
Keywords: differentiation; infectious diseases; macrophages; pluripotent stem cells; self‐renewal. |
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