Human iPS cell–derived hematopoietic progenitor cells induce T-cell anergy in in vitro–generated alloreactive CD8+ T cells

Kim, Eun‐Mi; Manzar, Gohar; Zavazava, Nicholas

doi:10.1182/blood-2012-11-467753

Cited by 30 publications

(35 citation statements)

References 52 publications

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“…Previous reports have also shown that human iPSCs display low expression of HLA class I molecules 23 and that iCD34 1 cells express nonclassical major histocompatibility complex molecules, such as HLA-G and HLA-E. 24 In this study, we also observed that iPSCs derived from monocytes of AA patients poorly expressed HLA molecules, but the HLA expression gradually increased as the cells differentiated into iCD34 1 cells, which allowed for the investigation of their sensitivity to CTLs. transplanted into the mice, we were able to determine the in vivo behavior of the individual clones in the mice, resulting in an unanticipated consistency of clonal behavior in the recipients.…”

Section: Discussionsupporting

confidence: 56%

Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack

et al. 2018

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Section: Discussionsupporting

confidence: 56%

Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack

et al. 2018

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“…Such low levels of MHC-I expression also reflect the undifferentiated nature of ESCs and their derivatives [42]. However, human iPSC-derived CD34 + hematopoietic progenitor cells have been found to poorly express MHC-I, which leads to T cell anergy [45]. Our results showed that the level of MHC-I expression in iPSCs was as low as that in ESCs.…”

Section: Discussionmentioning

confidence: 74%

Induced Pluripotent Stem Cells Can Effectively Differentiate into Multiple Functional Lymphocyte Lineages In Vivo with Negligible Bias

Lan

Wang

et al. 2016

Stem Cells and Development

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Lymphohematopoietic stem cells (L-HSCs) generated from self-somatic cell-derived induced pluripotent stem cells (iPSCs) are a potential source of cells for the treatment of hematological disorders. However, the generation of truly functional L-HSCs from iPSCs has yet to be achieved. Thus, whether iPSCs have the inherent potential to generate a normal differentiated phenotype and functional population of multiple lineages of terminally differentiated lymphocytes needs to be assessed. Here, we used tetraploid embryo complementation to provide a normal environment for the differentiation of hematopoietic cells from iPSCs and embryonic stem cells (ESCs). We then evaluated the characteristics, populations, and functions of lymphocytes derived from iPSCs, ESCs, and naïve isogenic C57BL/6 mice. The results showed that iPSC-derived lymphocytes (iPSLs) expressed normal levels of major histocompatibility complex-I (MHC-I) and exhibited a fully pluripotent capacity to differentiate into CD4(+) T, CD8(+) T, regulatory T, B, and natural killer cells. Following in vitro stimulation with either concanavalin A or an alloantigen, iPSLs exhibited the same capacities for proliferation and cytokine secretion as ESC-derived or isogenic lymphocytes. Furthermore, iPSC-derived bone marrow cells could differentiate into multiple lymphocyte lineages that reconstituted the lymphocyte population in syngeneic lethally irradiated recipient animals. Our results demonstrated that iPSCs have the inherent potential to differentiate into multiple lineages of functional lymphocytes without bias, and further support the practical application of iPSC-based treatments to hematological disorders.

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“…Induced pluripotent stem cells (iPSCs) are pluripotent cells derived from terminally differentiated cells by dedifferentiation. The generation of iPSCs creates the possibility of generating tissue-specific cells, including HSCs [63][64][65][66][67][68] or MSCs [69][70][71][72][73][74][75][76], but further study is required before clinical application of iPSCs can commence. Taken together, immune reconstruction and modification of genetic predisposition of hematopoietic stem cells are important for radical cure of IBD.…”

Section: Intestinal Stem Cells and Other Stem Cells In Ibdmentioning

confidence: 99%

Stem cell therapy for inflammatory bowel disease

2015

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Inflammatory bowel disease (IBD) could be curable by ''immune rest'' and correction of the genetic predisposition inherent in allogeneic hematopoietic stem cell transplantation. However, balancing risks against benefits remains challenging. The application of mesenchymal stem cells (MSCs) serving as a site-regulated ''drugstore'' is a recent concept, which suggests the possibility of an alternative treatment for many intractable diseases such as IBD. Depending on the required function of MSC, such as a cell provider, immune moderator, and/or trophic resource, MSC therapy should be optimized to maximize its therapeutic benefit. Therapeutic effects do not always require full engraftment of MSCs. Therefore, optimization of pleiotropic gut trophic factors produced by MSCs, which favoring not only regulating immune responses but also promoting tissue repair, must directly enhance new drug discoveries for treatment of IBD. Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and patients. However, the translational arm of stem cell science remains in a relatively primitive state.Although several clinical studies using MSCs have been initiated, early results suggest several inherent problems. In each study, optimization of MSC therapy appears to be the most urgent problem, and can be resolved only by scientifically unveiling the mechanisms of therapeutic action. In the present review, the authors outline how such information would facilitate the critical steps in the paradigm shift from basic research on stem cell biology to clinical practice of regenerative medicine for conquering IBD in the near future.

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Human iPS cell–derived hematopoietic progenitor cells induce T-cell anergy in in vitro–generated alloreactive CD8+ T cells

Abstract: Key Points Human iPSCs differentiate into CD34+ HPCs. iPSC-derived HPCs induce T-cell anergy.

Cited by 30 publications

References 52 publications

Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack

Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack

Induced Pluripotent Stem Cells Can Effectively Differentiate into Multiple Functional Lymphocyte Lineages In Vivo with Negligible Bias

Stem cell therapy for inflammatory bowel disease

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