Substrate-mediated reprogramming of human fibroblasts into neural crest stem-like cells and their applications in neural repair

Tseng, Ting-Chen; Hsieh, Fu-Yu; Dai, Niann‐Tzyy; Hsu, Shan‐hui

doi:10.1016/j.biomaterials.2016.06.020

Cited by 24 publications

(23 citation statements)

References 60 publications

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“…As Oct4 acts as a stem cell marker, 16 we evaluated the presence of HIF motifs around the Oct4-occupied regions in the data from vselMSCs and ESC. There were 16 genes that were expressed by more than 2- fold relative to GAPDH in vselMSCs, and there were seven shared genes that were uniquely common to vselMSCs and hESCs data sets (HIF-1, HIF-2, Oct4, bFGF, VEGF, Survivin, and Bcl2).…”

Section: Resultsmentioning

confidence: 99%

HIF-2α and Oct4 have synergistic effects on survival and myocardial repair of very small embryonic-like mesenchymal stem cells in infarcted hearts

et al. 2017

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Poor cell survival and limited functional benefits have restricted mesenchymal stem cell (MSC) efficacy for treating myocardial infarction (MI), suggesting that a better understanding of stem cell biology is needed. The transcription factor HIF-2α is an essential regulator of the transcriptional response to hypoxia, which can interact with embryonic stem cells (ESCs) transcription factor Oct4 and modulate its signaling. Here, we obtained very small embryonic-like mesenchymal stem cells (vselMSCs) from MI patients, which possessed the very small embryonic-like stem cells' (VSELs) morphology as well as ESCs' pluripotency. Using microarray analysis, we compared HIF-2α-regulated gene profiles in vselMSCs with ESC profiles and determined that HIF-2α coexpressed Oct4 in vselMSCs similarly to ESCs. However, this coexpression was absent in unpurified MSCs (uMSCs). Under hypoxic condition, vselMSCs exhibited stronger survival, proliferation and differentiation than uMSCs. Transplantation of vselMSCs caused greater improvement in cardiac function and heart remodeling in the infarcted rats. We further demonstrated that HIF-2α and Oct4 jointly regulate their relative downstream gene expressions, including Bcl2 and Survivin; the important pluripotent markers Nanog, Klf4, and Sox2; and Ang-1, bFGF, and VEGF, promoting angiogenesis and engraftment. Importantly, these effects were generally magnified by upregulation of HIF-2α and Oct4 induced by HIF-2α or Oct4 overexpression, and the greatest improvements were elicited after co-overexpressing HIF-2α and Oct4; overexpressing one transcription factor while silencing the other canceled this increase, and HIF-2α or Oct4 silencing abolished these effects. Together, these findings demonstrated that HIF-2α in vselMSCs cooperated with Oct4 in survival and function. The identification of the cooperation between HIF-2α and Oct4 will lead to deeper characterization of the downstream targets of this interaction in vselMSCs and will have novel pathophysiological implications for the repair of infarcted myocardium.

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Section: Resultsmentioning

confidence: 99%

HIF-2α and Oct4 have synergistic effects on survival and myocardial repair of very small embryonic-like mesenchymal stem cells in infarcted hearts

et al. 2017

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“…Han and Hsu reported that chitosan may provide an ECM‐like environment to drive the interaction and the morphological assembly between NSCs and MSCs and further improve the therapeutic efficacy for the treatment of neuronal disorders in vivo . A chitosan substrate was also used as a gene‐transfer vehicle to deliver naked FOXD3 plasmid into human fibroblasts and showed good feasibility in reprogramming somatic cells for neural repair . The chitosan‐mediated reprogramming method may be used as an easily accessible cellular source for treating neural diseases.…”

Section: Classes Of Nanomaterials For the Imaging And Treatment Of Nementioning

confidence: 99%

Nanomaterials in Neural‐Stem‐Cell‐Mediated Regenerative Medicine: Imaging and Treatment of Neurological Diseases

et al. 2018

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Patients are increasingly being diagnosed with neuropathic diseases, but are rarely cured because of the loss of neurons in damaged tissues. This situation creates an urgent clinical need to develop alternative treatment strategies for effective repair and regeneration of injured or diseased tissues. Neural stem cells (NSCs), highly pluripotent cells with the ability of self-renewal and potential for multidirectional differentiation, provide a promising solution to meet this demand. However, some serious challenges remaining to be addressed are the regulation of implanted NSCs, tracking their fate, monitoring their interaction with and responsiveness to the tissue environment, and evaluating their treatment efficacy. Nanomaterials have been envisioned as innovative components to further empower the field of NSC-based regenerative medicine, because their unique physicochemical characteristics provide unparalleled solutions to the imaging and treatment of diseases. By building on the advantages of nanomaterials, tremendous efforts have been devoted to facilitate research into the clinical translation of NSC-based therapy. Here, recent work on emerging nanomaterials is highlighted and their performance in the imaging and treatment of neurological diseases is evaluated, comparing the strengths and weaknesses of various imaging modalities currently used. The underlying mechanisms of therapeutic efficacy are discussed, and future research directions are suggested.

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“…Three groups of gene expression in chitosan‐mediated transfected cells were upregulated most significantly: stemness transcriptional factors including NANOG, OCT4, and Sox2, neural crest transcription factors including FOXD3, CD271, and SOX10, and neural lineage‐related genes including GFAP, nestin, and β‐tubulin. This substrate‐mediated trans‐differentiation method is effective and has low cytotoxicity, although its efficiency needs to be improved …”

Section: Trans‐differentiationmentioning

confidence: 99%

Materials for Neural Differentiation, Trans‐Differentiation, and Modeling of Neurological Disease

et al. 2018

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Neuron regeneration from pluripotent stem cells (PSCs) differentiation or somatic cells trans-differentiation is a promising approach for cell replacement in neurodegenerative diseases and provides a powerful tool for investigating neural development, modeling neurological diseases, and uncovering the mechanisms that underlie diseases. Advancing the materials that are applied in neural differentiation and trans-differentiation promotes the safety, efficiency, and efficacy of neuron regeneration. In the neural differentiation process, matrix materials, either natural or synthetic, not only provide a structural and biochemical support for the monolayer or three-dimensional (3D) cultured cells but also assist in cell adhesion and cell-to-cell communication. They play important roles in directing the differentiation of PSCs into neural cells and modeling neurological diseases. For the trans-differentiation of neural cells, several materials have been used to make the conversion feasible for future therapy. Here, the most current applications of materials for neural differentiation for PSCs, neuronal trans-differentiation, and neurological disease modeling is summarized and discussed.

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Substrate-mediated reprogramming of human fibroblasts into neural crest stem-like cells and their applications in neural repair

Cited by 24 publications

References 60 publications

HIF-2α and Oct4 have synergistic effects on survival and myocardial repair of very small embryonic-like mesenchymal stem cells in infarcted hearts

HIF-2α and Oct4 have synergistic effects on survival and myocardial repair of very small embryonic-like mesenchymal stem cells in infarcted hearts

Nanomaterials in Neural‐Stem‐Cell‐Mediated Regenerative Medicine: Imaging and Treatment of Neurological Diseases

Materials for Neural Differentiation, Trans‐Differentiation, and Modeling of Neurological Disease

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