Modeling Hematological Diseases and Cancer With Patient-Specific Induced Pluripotent Stem Cells

Kim, Huensuk; Schaniel, Christoph

doi:10.3389/fimmu.2018.02243

Cited by 7 publications

(6 citation statements)

References 139 publications

(123 reference statements)

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“…iPSCs have been used to model cancer cell heterogeneity, plasticity, tumor progression, drug resistance, and for drug screening (Campbell et al, 2020; Czerwińska et al, 2018; Kim, 2015; Sharkis et al, 2012). Also, iPSC reprogramming as a strategy to study cancer cell of origin has been successfully employed in several cancers with different strategies (Friedmann‐Morvinski & Verma, 2014; Czerwińska et al, 2018; Kim & Schaniel, 2018; Marin‐Navarro et al, 2018). One strategy to study cell of origin in cancer with iPSC is by direct reprogramming of tumor cells.…”

Section: Reprogramming Cancer Cells Into Ipsc: a Model For Assessing ...mentioning

confidence: 99%

Connecting the dots: Melanoma cell of origin, tumor cell plasticity, trans‐differentiation, and drug resistance

Castro‐Pérez

Singh

Sadangi

et al. 2023

Pigment Cell Melanoma Res

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Melanoma, a lethal malignancy that arises from melanocytes, exhibits a multiplicity of clinico‐pathologically distinct subtypes in sun‐exposed and non‐sun‐exposed areas. Melanocytes are derived from multipotent neural crest cells and are present in diverse anatomical locations, including skin, eyes, and various mucosal membranes. Tissue‐resident melanocyte stem cells and melanocyte precursors contribute to melanocyte renewal. Elegant studies using mouse genetic models have shown that melanoma can arise from either melanocyte stem cells or differentiated pigment‐producing melanocytes depending on a combination of tissue and anatomical site of origin and activation of oncogenic mutations (or overexpression) and/or the repression in expression or inactivating mutations in tumor suppressors. This variation raises the possibility that different subtypes of human melanomas (even subsets within each subtype) may also be a manifestation of malignancies of distinct cells of origin. Melanoma is known to exhibit phenotypic plasticity and trans‐differentiation (defined as a tendency to differentiate into cell lineages other than the original lineage from which the tumor arose) along vascular and neural lineages. Additionally, stem cell‐like properties such as pseudo‐epithelial‐to‐mesenchymal (EMT‐like) transition and expression of stem cell‐related genes have also been associated with the development of melanoma drug resistance. Recent studies that employed reprogramming melanoma cells to induced pluripotent stem cells have uncovered potential relationships between melanoma plasticity, trans‐differentiation, and drug resistance and implications for cell or origin of human cutaneous melanoma. This review provides a comprehensive summary of the current state of knowledge on melanoma cell of origin and the relationship between tumor cell plasticity and drug resistance.

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Section: Reprogramming Cancer Cells Into Ipsc: a Model For Assessing ...mentioning

confidence: 99%

Connecting the dots: Melanoma cell of origin, tumor cell plasticity, trans‐differentiation, and drug resistance

Castro‐Pérez

Singh

Sadangi

et al. 2023

Pigment Cell Melanoma Res

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“…Second, the myeloid lineage is dominant, and lymphoid hematopoiesis have been less well reconstituted. Thus, most in vitro iPSC hematopoietic disease models are myeloid types, such as MPD, acute myeloid leukemia (AML), MDS and bone marrow failures [8]. Thirdly, the dominant types of hemoglobin in iPSC-derived erythrocytes are neonatal (HbE) or fetal (HbF), not adult-type HbA [33,[40][41][42].…”

Section: Hematopoiesis In Vivo Vs Hematopoiesis In Vitro From Ipscsmentioning

confidence: 99%

“…The versatility of iPSCs is applicable to the field of hematopoiesis. One way is to recapitulate hematopoietic diseases, ranging from monogenic congenital diseases or myeloproliferative diseases (MPD) to multifactorial hematopoietic malignancies and bone marrow failures, by using iPSCs established from patients [ 7 , 8 ]. These models will contribute to uncovering the unknown pathogenesis or drug testing, thus leading to novel treatment modalities for the diseases.…”

Section: Introductionmentioning

confidence: 99%

Generation and manipulation of human iPSC-derived platelets

Sugimoto

Eto

2021

Cell. Mol. Life Sci.

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The discovery of iPSCs has led to the ex vivo production of differentiated cells for regenerative medicine. In the case of transfusion products, the derivation of platelets from iPSCs is expected to complement our current blood-donor supplied transfusion system through donor-independent production with complete pathogen-free assurance. This derivation can also overcome alloimmune platelet transfusion refractoriness by resulting in autologous, HLA-homologous or HLA-deficient products. Several developments were necessary to produce a massive number of platelets required for a single transfusion. First, expandable megakaryocytes were established from iPSCs through transgene expression. Second, a turbulent-type bioreactor with improved platelet yield and quality was developed. Third, novel drugs that enabled efficient feeder cell-free conditions were developed. Fourth, the platelet-containing suspension was purified and resuspended in an appropriate buffer. Finally, the platelet product needed to be assured for competency and safety including non-tumorigenicity through in vitro and in vivo preclinical tests. Based on these advancements, a clinical trial has started. The generation of human iPSC-derived platelets could evolve transfusion medicine to the next stage and assure a ubiquitous, safe supply of platelet products. Further, considering the feasibility of gene manipulations in iPSCs, other platelet products may bring forth novel therapeutic measures.

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“…Direct conversion approaches to generate cells of the hematopoietic lineage from fibroblasts using a one-step approach or directed differentiation from human embryonic stem cells have been used as an alternative to somatic cell reprogramming followed by hematopoietic differentiation of iPSCs [51]. The use of iPSC model for hematological disorders with a focus on patient-specific iPSCs has been reviewed [50,[52][53][54]. The generation of isogenic pairs of normal and mutated iPSC lines using gene editing methodology helps in understanding the key role of specific mutations.…”

Section: Transposon-based Insertional Mutagenesismentioning

confidence: 99%

Harnessing the Power of Induced Pluripotent Stem Cells and Gene Editing Technology: Therapeutic Implications in Hematological Malignancies

Sidhu

Barwe

Pillai

et al. 2021

Cells

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In vitro modeling of hematological malignancies not only provides insights into the influence of genetic aberrations on cellular and molecular mechanisms involved in disease progression but also aids development and evaluation of therapeutic agents. Owing to their self-renewal and differentiation capacity, induced pluripotent stem cells (iPSCs) have emerged as a potential source of short in supply disease-specific human cells of the hematopoietic lineage. Patient-derived iPSCs can recapitulate the disease severity and spectrum of prognosis dictated by the genetic variation among patients and can be used for drug screening and studying clonal evolution. However, this approach lacks the ability to model the early phases of the disease leading to cancer. The advent of genetic editing technology has promoted the generation of precise isogenic iPSC disease models to address questions regarding the underlying genetic mechanism of disease initiation and progression. In this review, we discuss the use of iPSC disease modeling in hematological diseases, where there is lack of patient sample availability and/or difficulty of engraftment to generate animal models. Furthermore, we describe the power of combining iPSC and precise gene editing to elucidate the underlying mechanism of initiation and progression of various hematological malignancies. Finally, we discuss the power of iPSC disease modeling in developing and testing novel therapies in a high throughput setting.

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Modeling Hematological Diseases and Cancer With Patient-Specific Induced Pluripotent Stem Cells

Cited by 7 publications

References 139 publications

Connecting the dots: Melanoma cell of origin, tumor cell plasticity, trans‐differentiation, and drug resistance

Connecting the dots: Melanoma cell of origin, tumor cell plasticity, trans‐differentiation, and drug resistance

Generation and manipulation of human iPSC-derived platelets

Harnessing the Power of Induced Pluripotent Stem Cells and Gene Editing Technology: Therapeutic Implications in Hematological Malignancies

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