Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell–derived lin–CD34+CD43+CD45+ progenitors

Choi, Kwang-Soo; Vodyanik, Maxim A.; Slukvin, Igor I.

doi:10.1172/jci38591

Cited by 192 publications

(210 citation statements)

References 47 publications

Supporting

Mentioning

199

Contrasting

Unclassified

Order By: Relevance

“…Thus, if a sufficient number of neutrophils could be prepared, allogenic neutrophils could be a potential source of cell therapy for cirrhosis. Development of neutrophil differentiation from human‐induced pluripotent stem cells30, 31 would be supportive of such a strategy. Furthermore, delivery of chemoattractive chemokines for neutrophils as well as MMP8 and MMP9 in the liver might be an alternative strategy for the treatment of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils alleviate fibrosis in the CCl4‐induced mouse chronic liver injury model

Saijou

Enomoto

Matsuda

et al. 2018

Hepatology Communications

View full text Add to dashboard Cite

Tribbles pseudokinase 1 (Trib1) is a negative regulator of CCAAT/enhancer binding protein α (C/EBPα) and is known to induce granulopoiesis while suppressing monocyte differentiation. Loss of Trib1 was previously shown to increase the neutrophil population in the spleen but lead to M2‐like macrophage reduction. Because M2 macrophages are anti‐inflammatory and promote tissue repair by producing fibrogenic factors, we investigated liver fibrosis in Trib1‐deficient mice. Interestingly, loss of Trib1 suppressed fibrosis in the CCl4‐induced chronic liver injury model. Trib1 knockout increased neutrophils but had a minimal effect on the macrophage population in the liver. Hepatic expressions of neutrophil matrix metalloproteinases (Mmp)8 and Mmp9 were increased, but the production of fibrogenic factors, including transforming growth factor β1, was not affected by loss of Trib1. These results suggest that neutrophils are responsible for the suppression of fibrosis in Trib1‐deficient liver. Consistently, transplantation of Trib1‐deficient bone marrow cells into wild‐type mice alleviated CCl4‐induced fibrosis. Furthermore, expression of chemokine (C‐X‐C motif) ligand 1 (Cxcl1) by adeno‐associated viral vector in the normal liver recruited neutrophils and suppressed CCl4‐induced fibrosis; infusion of wild‐type neutrophils in CCl4‐treated mice also ameliorated fibrosis. Using recombinant adeno‐associated virus‐mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4‐induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis. (Hepatology Communications 2018;2:703‐717)

show abstract

Section: Discussionmentioning

confidence: 99%

Neutrophils alleviate fibrosis in the CCl4‐induced mouse chronic liver injury model

Saijou

Enomoto

Matsuda

et al. 2018

Hepatology Communications

View full text Add to dashboard Cite

show abstract

“…Although conventional DC have been differentiated previously from human iPS cells, 14,15 the reliance on animal products and the mouse OP-9 stromal cell line precludes their downstream clinical application. We therefore directed the differentiation of C19 towards the DC lineage by adapting protocols we had established previously for the differentiation of DC from human ES cells in the absence of animal products with the sole exception of matrigel, required for the routine passage of undifferentiated ES cells and iPS cells.…”

Section: Differentiation Of Clinical-grade DC From Human Ips Cellsmentioning

confidence: 99%

Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141+XCR1+ dendritic cells

Silk

Ichiryu

et al. 2011

Gene Ther

View full text Add to dashboard Cite

Monocyte-derived dendritic cells (moDC) have been widely used in cancer immunotherapy but show significant donor-to-donor variability and low capacity for the cross-presentation of tumour-associated antigens (TAA) to CD8 þ T cells, greatly limiting the success of this approach. Given recent developments in induced pluripotency and the relative ease with which induced pluripotent stem (iPS) cell lines may be generated from individuals, we have succeeded in differentiating dendritic cells (DC) from human leukocyte antigen (HLA)-A*0201 þ iPS cells (iPS cell-derived DC (ipDC)), using protocols compliant with their subsequent clinical application. Unlike moDC, a subset of ipDC was found to coexpress CD141 and XCR1 that have been shown previously to define the human equivalent of mouse CD8a þ DC, in which the capacity for cross-presentation has been shown to reside. Accordingly, ipDC were able to cross-present the TAA, Melan A, to a CD8 þ T-cell clone and stimulate primary Melan A-specific responses among naïve T cells from an HLA-A*0201 þ donor. Given that CD141 þ XCR1 þ DC are present in peripheral blood in trace numbers that preclude their clinical application, the ability to generate a potentially unlimited source from iPS cells offers the possibility of harnessing their capacity for cross-priming of cytotoxic T lymphocytes for the induction of tumourspecific immune responses.

show abstract

“…Although hematopoietic differentiation has been explored, [15][16][17] no terminal erythroid differentiation has been reported to date.…”

Section: Introductionmentioning

confidence: 99%

Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine

Lapillonne¹,

Kobari²,

Mazurier³

et al. 2010

Haematologica

213

253

View full text Add to dashboard Cite

The online version of this article has a a Supplementary Appendix. BackgroundEx vivo manufacture of red blood cells from stem cells is a potential means to ensure an adequate and safe supply of blood cell products. Advances in somatic cell reprogramming of human induced pluripotent stem cells have opened the door to generating specific cells for cell therapy. Human induced pluripotent stem cells represent a potentially unlimited source of stem cells for erythroid generation for transfusion medicine. Design and MethodsWe characterized the erythroid differentiation and maturation of human induced pluripotent stem cell lines obtained from human fetal (IMR90) and adult fibroblasts (FD-136) compared to those of a human embryonic stem cell line (H1). Our protocol comprises two steps: (i) differentiation of human induced pluripotent stem cells by formation of embryoid bodies with indispensable conditioning in the presence of cytokines and human plasma to obtain early erythroid commitment, and (ii) differentiation/maturation to the stage of cultured red blood cells in the presence of cytokines. The protocol dispenses with major constraints such as an obligatory passage through a hematopoietic progenitor, co-culture on a cellular stroma and use of proteins of animal origin. ResultsWe report for the first time the complete differentiation of human induced pluripotent stem cells into definitive erythrocytes capable of maturation up to enucleated red blood cells containing fetal hemoglobin in a functional tetrameric form. ConclusionsRed blood cells generated from human induced pluripotent stem cells pave the way for future development of allogeneic transfusion products. This could be done by banking a very limited number of red cell phenotype combinations enabling the safe transfusion of a great number of immunized patients. © F e r r a t a S t o r t i F o u n d a t i o n

show abstract

Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell–derived lin–CD34+CD43+CD45+ progenitors

Cited by 192 publications

References 47 publications

Neutrophils alleviate fibrosis in the CCl4‐induced mouse chronic liver injury model

Neutrophils alleviate fibrosis in the CCl4‐induced mouse chronic liver injury model

Cross-presentation of tumour antigens by human induced pluripotent stem cell-derived CD141+XCR1+ dendritic cells

Red blood cell generation from human induced pluripotent stem cells: perspectives for transfusion medicine

Contact Info

Product

Resources

About