Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation

Paes, Bárbara Cristina Martins Fernandes; Moço, Pablo Diego; Pereira, Cristiano G.; Porto, Geciâne Silveira; Russo, Elisa Maria de Sousa; Reis, Luiza Campos; Covas, Dimas Tadeu; Picanço‐Castro, Virgínia

doi:10.1007/s10565-016-9377-2

Cited by 28 publications

(18 citation statements)

References 110 publications

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“…Hematopoietic differentiation from hiPSCs enables the investigation of early development and promises to be a source of cellbased therapies in the future [5,23]. Besides the generation of distinct hematopoietic lineages, the generation of HSCs from hiPSCs is a central purpose of biomedical research and transfusion medicine in particular [24,25].…”

Section: Discussionmentioning

confidence: 99%

Emergence of CD43-Expressing Hematopoietic Progenitors from Human Induced Pluripotent Stem Cells

Kessel¹,

Bluemke²,

Schöler³

et al. 2017

Transfus Med Hemother

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Background: The ex vivo generation of human hematopoietic stem cells (HSCs) with long-term repopulating capacity and multi-lineage differentiation potential represents the holy grail of hematopoiesis research. In principle, human induced pluripotent stem cells (hiPSCs) provide the tool for both studying molecular mechanisms of hematopoietic development and the ex vivo production of ‘true' HSCs for transplantation purposes and lineage-specific cells, e.g. red blood cells, for transfusion purposes. CD43-expressing cells have been reported as the first hematopoietic cells during development, but whether or not these possess multilineage differentiation and long-term engraftment potential is incompletely understood. Methods: We performed ex vivo generation of hematopoietic cells from hiPSCs using an embryoid body(EB)-based, xeno-product-free differentiation protocol. We investigated the multilineage differentiation potential of different FACS-sorted CD43-expressing cell subsets by colony-forming assays in semisolid media. Further, erythroid differentiation was investigated in more detail using established protocols. Results: By using CD43, we were able to measure hematopoietic induction efficiency during hiPSC-derived EB differentiation. Further, we determined CD43+ cells as the cell population of origin for in vitro erythropoiesis. Furthermore, colony formation demonstrates that the multipotent hematopoietic stem and progenitor cell fraction is particulary enriched in the CD43^hi CD45+ population.

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Section: Discussionmentioning

confidence: 99%

Emergence of CD43-Expressing Hematopoietic Progenitors from Human Induced Pluripotent Stem Cells

Kessel¹,

Bluemke²,

Schöler³

et al. 2017

Transfus Med Hemother

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“…First, iPSCs are applied for research as models of disease development, so called "disease-in-a-dish" [3]. Second, iPSCs provided new possibilities in drug screening for efficacy and potential toxicities [4]. Third, iPSC technology is widely applied in regenerative medicine for the development of stem cell-based therapies, including the therapies of the skin, heart, neural tissues, eye, and blood diseases [5].…”

Section: Introductionmentioning

confidence: 99%

Donor information in research and drug evaluation with induced pluripotent stem cells (iPSCs)

Orzechowski¹,

Schochow²,

Kühl

et al. 2020

Stem Cell Res Ther

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Background: The discovery of induced pluripotent stem cells (iPSCs) opened the possibilities for reprogramming cells back to a pluripotent state. Because of no apparent ethical issues connected with donation and derivation of biomaterial, iPSCs are considered as a research alternative to ethically highly disputed human embryonic stem cells (hESCs). However, the unique character of iPSCs leads to numerous ethical considerations, which mainly concern the issue of donor information and consent for the use of biospecimen in research and drug evaluation. Methods: For the purpose of this analysis, we conducted a review of the literature in the PubMed/MEDLINE and Web of Science databases. The search algorithm led to the identification of 1461 results. After removing duplicates and screening of title and abstract, 90 articles were found to be relevant to the study's objective. Full texts of these articles were apprised and 62 articles were excluded at this step for not properly addressing the study's objective. In the final step, 28 articles were included in the analysis. Analyzed were both research and non-research manuscripts published in peer-reviewed journals. Results: In the case of iPSC research, the information process should be guided by general frameworks established for research on human subjects but also by specific characteristics of iPSCs. We determined four main domains and 12 thematic subdomains that should be included in donor information. Our results show that majority of authors agree to the content of information with regard to the areas of general information, storage of cells, and protection of privacy. Two main issues that are discussed in the literature are donor's consent for use in future studies and the process of donor information. Conclusions: Given the unique character of iPSCs and the possibility of their various uses in the future, the content of donor information should contain specific information central to iPSC research. Effective methods of communicating information to donors should combine written and oral information with the possible use of multimedia.

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“…During the past decade, enormous progress has been made in the ex vivo manufacture of human RBCs [7][8][9][10][11]. Hematopoietic stem cells (HSC) obtained from cord blood and bone marrow have been used to produce functional enucleated RBCs [12][13][14][15][16].…”

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confidence: 99%

Human induced pluripotent stem cell line banking for the production of rare blood type erythrocytes

et al. 2020

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Background: The in vitro production of mature human red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) has been the focus of research to meet the high demand for blood transfusions. However, limitations like high costs and technological requirements restrict the use of RBCs produced by iPSC differentiation to specific circumstances, such as for patients with rare blood types or alloimmunized patients. In this study, we developed a detailed protocol for the generation of iPSC lines derived from peripheral blood of donors with O D-positive blood and rare blood types (D-and Jr(a-)) and subsequent erythroid differentiation. Methods: Mononuclear cells separated from the peripheral blood of O D-positive and rare blood type donors were cultured to produce and expand erythroid progenitors and reprogrammed into iPSCs. A 31-day serum-free, xeno-free erythroid differentiation protocol was used to generate reticulocytes. The stability of iPSC lines was confirmed with chromosomal analysis and RT-PCR. Morphology and cell counts were determined by microscopy observations and flow cytometry. Results: Cells from all donors were successfully used to generate iPSC lines, which were differentiated into erythroid precursors without any apparent chromosomal mutations. This differentiation protocol resulted in moderate erythrocyte yield per iPSC. Conclusions: It has previously only been hypothesized that erythroid differentiation from iPSCs could be used to produce RBCs for transfusion to patients with rare blood types or who have been alloimmunized. Our results demonstrate the feasibility of producing autologous iPSC-differentiated RBCs for clinical transfusions in patients without alternative options.

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Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation

Cited by 28 publications

References 110 publications

Emergence of CD43-Expressing Hematopoietic Progenitors from Human Induced Pluripotent Stem Cells

Emergence of CD43-Expressing Hematopoietic Progenitors from Human Induced Pluripotent Stem Cells

Donor information in research and drug evaluation with induced pluripotent stem cells (iPSCs)

Human induced pluripotent stem cell line banking for the production of rare blood type erythrocytes

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