Induction Of Pluripotent Stem Cells From Adult Human Fibroblasts By Defined Factors

Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Cell (Impact Factor: 32.24). 12/2007; 131(5):861-72. DOI: 10.1016/j.cell.2007.11.019
Source: PubMed


Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.

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Available from: Kiichiro Tomoda, Jul 28, 2014
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    • "On the other hand, iPSCs are classically generated by reprogramming fibroblasts by retroviral transduction of the transcription factors Klf4, Sox2, Oct4, and c-Myc. Once generated, iPSCs show all features of pluripotent ESCs and are capable of differentiation into cells of all three embryonic germ layers189190191. The possibility of patient-specific iPSCs offers great hope for generating genetically matched patient-specific lung progenitor cells, with the opportunity for patient specific regenerative cell therapy and drug screening as well as in vitro modelling of human diseases[87]. "
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    ABSTRACT: The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases.
    Full-text · Article · Feb 2016 · International Journal of Molecular Sciences
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    • "The generation of the human iPSC line, PG64SV.2, was carried out using non-integrative Sendai viruses containing the reprogramming factors, Oct3/4, Sox2, cMyc, Klf4 (Takahashi et al., 2007). For this purpose , fibroblasts from a patient with a defect of intergenomic communication (Hirano et al., 2001) were provided by EuroBiobank. "
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    ABSTRACT: Human iPSC line PG64SV.2 was generated from fibroblasts of a patient with a defect of intergenomic communication. This patient harbored a homozygous mutation (c.2243G>C; p.Trp748Ser) in the gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma gene (POLG). Reprogramming factors Oct3/4, Sox2, Klf4, and cMyc were delivered using a non integrative methodology that involves the use of Sendai virus.
    Full-text · Article · Jan 2016 · Stem Cell Research
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    • "Greater knowledge of the expression of these genes may be useful in future developmental biology studies or in directed differentiation experiments. Finally, given the need for new therapeutics and the exciting potential of regenerative medicine efforts, we sought to determine the expression of genes known to be important in stem cell biology232425. Previous studies note the expression of histatin-1 in ALG[18]and, minimally on the ocular surface, though there are conflicting results regarding expression on the ocular surface29303132. "
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    ABSTRACT: Background: Study of human lacrimal cell biology is limited by poor access to tissue samples, heterogeneous cell composition of tissue and a lack of established lacrimal epithelial markers. In order to further our understanding of lacrimal cell biology, we sought to find a better marker for human lacrimal epithelial cells, compared to what has been reported in the literature. Methods: We utilized human Muller's muscle conjunctival resection (MMCR) specimens containing accessory lacrimal gland (ALG) and cadaveric main lacrimal gland (MLG) as sources of lacrimal tissue. Candidate markers were sought using human ALG tissue from MMCR specimens, isolated by laser capture microdissection (LCM). Affymetrix® analysis was performed on total RNA isolated from FFPE samples to profile transcription in ALG. MMCR tissue sections were assessed by immunofluorescence using antibodies for histatin-1, lactoferrin, E-cadherin (E-cad) and alpha-smooth muscle actin (ASMA). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was performed to analyze the expression of histatin-1, E-cad and lactoferrin from cadaveric MLG. Results: Histatin-1 is expressed in ALG and MLG, localizes to lacrimal epithelium, and to a greater degree than do other putative lacrimal epithelial markers. Conclusions: Histatin-1 is a good marker for human lacrimal epithelium in ALG and MLG and can be used to identify lacrimal cells in future studies.
    Preview · Article · Jan 2016 · PLoS ONE
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