2021
DOI: 10.1371/journal.pone.0250107
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Generation of cryopreserved macrophages from normal and genetically engineered human pluripotent stem cells for disease modelling

Abstract: Macrophages are innate immune cells that play critical roles in tissue homeostasis, inflammation, and immune oncology. Macrophages differentiated from human induced pluripotent stem cells (iPSCs) overcome many limitations of using peripheral blood derived macrophages. The ability to scale up and cryopreserve a large amount of end stage macrophages from single clonal iPSCs from normal and disease specific donors offers a unique opportunity for genomic analysis and drug screening. The present study describes the… Show more

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Cited by 6 publications
(7 citation statements)
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“…Munn and co-authors [ 57 ] modeled several neurodegenerative disorders, including PD, by introducing mutations SNCA A53T (PD-associated), GRN2/GRN R493X (associated with neuronal ceroid lipofuscinosis) and MECP2-Knockout (responsible for Rett syndrome) to the same isogenic iPSC line and differentiating the modified iPSCs to iMphs (EB-F). All iMphs expressed macrophage-specific markers, were phagocytic and responded to specific stimuli.…”
Section: Hereditary Disease Modelingmentioning
confidence: 99%
See 1 more Smart Citation
“…Munn and co-authors [ 57 ] modeled several neurodegenerative disorders, including PD, by introducing mutations SNCA A53T (PD-associated), GRN2/GRN R493X (associated with neuronal ceroid lipofuscinosis) and MECP2-Knockout (responsible for Rett syndrome) to the same isogenic iPSC line and differentiating the modified iPSCs to iMphs (EB-F). All iMphs expressed macrophage-specific markers, were phagocytic and responded to specific stimuli.…”
Section: Hereditary Disease Modelingmentioning
confidence: 99%
“…Therefore, the specificity and the stability of modifications introduced into iPSCs need to be additionally and carefully controlled at the iMph level. Furthermore, the phenotypes, transcriptomic signatures and functional activities of genetically modified iMphs should be carefully examined, as they may be influenced by the introduced mutations [ 57 ].…”
Section: Imph-based Cell Therapy: Safety and Other Questions To Explorementioning
confidence: 99%
“…In the past few years, the differentiation schemes of iPSC-derived macrophages (IPSDMs) have been constantly inproved and used in disease models [10][11][12][13][14][15], macrophagepathogen interaction modeling [16,17], and cell therapy [18]. Initially, cells in some methods were required to coculture with OP9 mouse stromal cells [10,19,20], but this approach was gradually obsoleted because of the use of xenogeneic cells that limited the clinical application.…”
Section: Introductionmentioning
confidence: 99%
“…The differentiation efficiency was not consistent, and the protocol was laborious. To improve the efficiency of differentiation and to standardize macrophage products, we developed a method of cryopreserving PSC-MP (34). For this purpose, we established PSC-derived immortalized myeloid cell lines (PSC-MLs) by introducing MYC, BMI1, and MDM2 into iPSC-derived floating monocytic cells (Figure 1) (6, 10).…”
Section: Pluripotent Stem Cell-derived Macrophagesmentioning
confidence: 99%
“…In addition to monocytes/macrophages, neutrophils are important innate immune cells that are involved in the pathogenesis of autoinflammatory disorders. While it is now possible to cryopreserve PSC-MPs at the progenitor level (6,10), or as the final product (34), cryopreservation of PSC-derived neutrophils has yet to be reported. Improvements in the differentiation protocol may enable the utilization of PSC-derived neutrophils for autoinflammatory disease research.…”
Section: Future Directionsmentioning
confidence: 99%