Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells

Hu, Kejin; Yu, Junying; Suknuntha, Kran; Tian, Shulan; Montgomery, Karen Dyer; Choi, Kyung Dal; Stewart, Ron; Thomson, James A.; Slukvin, Igor I.

doi:10.1182/blood-2010-07-298331

Cited by 232 publications

(200 citation statements)

References 35 publications

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“…The efficiencies for reprogramming adult blood MNCs are generally 20-50 folds lower; however, multiple iPSC lines can be established from a few milliliters of blood samples [10]. In another independent study, bone marrow MNCs were also efficiently reprogrammed to iPSCs using similar episomal vectors although a different expansion condition was employed before plasmid transfection [11]. In both studies, the established iPSCs have been shown to be free of V(D)J rearrangement and vector DNA in the genomes.…”

Section: Generation Of Patient-specific Ipscsmentioning

confidence: 87%

“…However, further improvement of the methods is needed to enhance the reprogramming efficiencies and to make them reproducible widely in other laboratories [7,8]. Plasmidmediated reprogramming is currently the most reliable method for integration-free reprogramming [9][10][11]. The procedure is also less complicated than viral protocols which require the separated steps of virus-making and viral infection of target cells; therefore, more suitable as a routine laboratory procedure.…”

Section: Generation Of Patient-specific Ipscsmentioning

confidence: 99%

“…Blood sample collection and storage are among the routine procedures in hospitals and clinics. Therefore, significant efforts have been made to develop efficient and safe procedures for reprogramming various types of blood cells (Table 1) [10,11,[13][14][15][16][17][18][19][20][21]. Umbilical cord blood (UCB) cell banks provide another rich source for cells with diverse HLA types.…”

Section: Generation Of Patient-specific Ipscsmentioning

confidence: 99%

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Promise and challenges of human iPSC-based hematologic disease modeling and treatment

Chou

Cheng

2012

Int J Hematol

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Postnatal hematopoietic stem cells (HSCs) from umbilical cord blood and adult marrow/blood have been successfully used for treating various human diseases in the past several decades. However, the availability of optimal numbers of HSCs from autologous patients or allogeneic donors with adequate match remains a great barrier to improve and extend HSC and marrow transplantation to more needing patients. In addition, the inability to expand functional human HSCs to sufficient quantity in the laboratory has hindered our research and understanding of human HSCs and hematopoiesis. Recent development in reprogramming technology has provided patient-specific pluripotent stem cells (iPSCs) as a powerful enabling tool for modeling disease and developing therapeutics. Studies have demonstrated the potential of human iPSCs, which can be expanded exponentially and amenable for genome engineering, for using in modeling both inherited and acquired blood diseases. Proof-of-principle studies have also shown the feasibility of iPSCs in gene and cell therapy. Here, we review the recent development in iPSC-based blood disease modeling, and discuss the unsolved issues and challenges in this new and promising field.

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Section: Generation Of Patient-specific Ipscsmentioning

confidence: 87%

Section: Generation Of Patient-specific Ipscsmentioning

confidence: 99%

Section: Generation Of Patient-specific Ipscsmentioning

confidence: 99%

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Promise and challenges of human iPSC-based hematologic disease modeling and treatment

Chou

Cheng

2012

Int J Hematol

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“…Recent data clearly demonstrated that Lin28, a major pluripotency regulator, is involved on the progression of CML from a chronic to blast phase (13). Interestingly, the overexpression of pluripotency genes, among which, Lin28, in CML cells has been shown to allow generation of ES-like pluripotent stem cells (iPSC) with the ability to generate hematopoietic cells in vitro (24). These findings establish therefore the proof of concept of the feasibility of programming of malignant cells and show also the close relationships between pluripotency and malignancy.…”

Section: Future Directionsmentioning

confidence: 99%

Chronic Myeloid Leukemia Stem Cells: Lessons from a Lead Paradigm

Turhan¹

2012

AACR Education book

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“…Uncontrolled silencing of retroviral vectors (RVs) also compromises reprogramming efficiency and quality. Ever since the establishment of iPSC technology, great efforts have been invested in developing new approaches to address the various issues mentioned previously [4][5][6]. To achieve these goals, many distinct technologies are employed in current reprogramming protocols.…”

mentioning

confidence: 99%

Vectorology and Factor Delivery in Induced Pluripotent Stem Cell Reprogramming

2014

Stem Cells and Development

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Induced pluripotent stem cell (iPSC) reprogramming requires sustained expression of multiple reprogramming factors for a limited period of time (10-30 days). Conventional iPSC reprogramming was achieved using lentiviral or simple retroviral vectors. Retroviral reprogramming has flaws of insertional mutagenesis, uncontrolled silencing, residual expression and re-activation of transgenes, and immunogenicity. To overcome these issues, various technologies were explored, including adenoviral vectors, protein transduction, RNA transfection, minicircle DNA, excisable PiggyBac (PB) transposon, Cre-lox excision system, negative-sense RNA replicon, positive-sense RNA replicon, Epstein-Barr virus-based episomal plasmids, and repeated transfections of plasmids. This review provides summaries of the main vectorologies and factor delivery systems used in current reprogramming protocols.

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Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells

Cited by 232 publications

References 35 publications

Promise and challenges of human iPSC-based hematologic disease modeling and treatment

Promise and challenges of human iPSC-based hematologic disease modeling and treatment

Chronic Myeloid Leukemia Stem Cells: Lessons from a Lead Paradigm

Vectorology and Factor Delivery in Induced Pluripotent Stem Cell Reprogramming

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