Generation of human induced pluripotent stem cells from dermal fibroblasts

Lowry, William E.; Richter, Laura; Yachechko, Robin; Pyle, April D.; Tchieu, Jason; Sridharan, Rupa; Clark, Amander T.; Plath, Kathrin

doi:10.1073/pnas.0711983105

Cited by 942 publications

(728 citation statements)

References 21 publications

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“…The recently demonstrated dedifferentiation capacity from terminally differentiated mammalian somatic cells via genetic manipulations to induced pluripotent stem cells (iPSCs) has great impact on cell-based therapy [60][61][62]. The cells are forced to express specific transcription factors, such as Oct4, Sox-2, c-Myc, and Klf4, and subsequently reprogrammed to exhibit features reminiscent of embryonic stem cells, termed iPS.…”

Section: Discussionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and micro-RNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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“…It was recently revealed that ES cell-like pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, can be generated by the simultaneous introduction of several genes for reprogramming factors, such as Oct3/4, Sox2, Klf4, and c-Myc, into somatic cells [13][14][15][16][17][18][19][20]. The issue of histoincompatibility between patients to be treated and ES cells may be overcome by the generation of iPS cells from somatic cells of the patients such as fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Dendritic Cells and Macrophages Generated by Directed Differentiation from Mouse Induced Pluripotent Stem Cells

et al. 2009

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Methods have been established to generate dendritic cells (DCs) from mouse and human embryonic stem (ES) cells. We designated them as ES-DCs and mouse models have demonstrated the induction of anti-cancer immunity and prevention of autoimmune disease by in vivo administration of genetically engineered ES-DCs. For the future clinical application of ES-DCs, the histoincompatibility between patients to be treated and available human ES cells and the ethical concerns associated with human ES cells may be serious obstacles. However, recently developed induced pluripotent stem (iPS) cell technology is expected to resolve these issues. This report describes the generation and characterization of DCs derived from mouse iPS cells. The iPS cell-derived DCs (iPS-DCs) possessed the characteristics of DCs including the capacity of T-cell-stimulation, antigen-processing and presentation and cytokine production. DNA microarray analyses revealed the upregulation of genes related to antigen-presenting functions during differentiation into iPS-DCs and similarity in gene expression profile in iPS-DCs and bone marrow cell-derived DCs. Genetically modified iPS-DCs expressing antigenic protein primed T-cells specific to the antigen in vivo and elicited efficient antigen-specific antitumor immunity. In addition, macrophages were generated from iPS cells (iPS-MP). iPS-MP were comparable with bone marrow cell-derived macrophages in the cell surface phenotype, functions, and gene expression profiles.

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“…iPS cells have been generated from human somatic cells, like fibroblasts, peripheral blood cells, keratinocytes, neural stem cells and others (Aasen et al 2008;Kim et al 2009;Loh et al 2009;Lowry et al 2008;Park et al 2008;Takahashi et al 2007;Yu et al 2007). These cells may provide an alternative source of stem cells for the treatment of type I diabetes.…”

Section: Differentiation Of Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Pokrywczyńska

Krzyzanowska

Jundziłł

et al. 2013

Arch. Immunol. Ther. Exp.

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Diabetes mellitus is one of the most serious public health challenges of the twenty-first century. Allogenic islet transplantation is an efficient therapy for type 1 diabetes. However, immune rejection, side effects of immunosuppressive treatment as well as lack of sufficient donor organs limits its potential. In recent years, several promising approaches for generation of new pancreatic b cells have been developed. This review provides an overview of current status of pancreatic and extra-pancreatic stem cells differentiation into insulin-producing cells and the possible application of these cells for diabetes treatment. The PubMed database was searched for English language articles published between 2001 and 2012, using the keyword combinations: diabetes mellitus, differentiation, insulin-producing cells, stem cells.

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Generation of human induced pluripotent stem cells from dermal fibroblasts

Cited by 942 publications

References 21 publications

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

Characterization of Dendritic Cells and Macrophages Generated by Directed Differentiation from Mouse Induced Pluripotent Stem Cells

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

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