Pathway for Differentiation of Human Embryonic Stem Cells to Vascular Cell Components and Their Potential for Vascular Regeneration

Sone, Masakatsu; Itoh, Hiroshi; Yamahara, Kenichi; Yamashita, Jun; Yurugi-Kobayashi, Takami; Nonoguchi, Akane; Suzuki, Yutaka; Chao, Ting‐Hsing; Sawada, Naoki; Fukunaga, Yasutomo; Miyashita, Kazutoshi; Park, Kwijun; Oyamada, Naofumi; Sawada, Naoya; Taura, Daisuke; Tamura, Naohisa; Kondo, Yasushi; Nito, Shinji; Suemori, Hirofumi; Nakatsuji, Norio; Nishikawa, Shin Ichi; Nakao, Kazuwa

doi:10.1161/atvbaha.107.143149

Cited by 132 publications

(113 citation statements)

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“…Recently, we developed a similar vascular cell differentiation system using human ES cells 38 and applied that to vascular regeneration. 39 These differentiation systems for pluripotent stem cells would be applicable to human iPS cells and would greatly contribute to the generation of new-mode cardiovascular regenerative medicine with the use of iPS cells.…”

Section: Discussionmentioning

confidence: 99%

Directed and Systematic Differentiation of Cardiovascular Cells From Mouse Induced Pluripotent Stem Cells

et al. 2008

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Background-Induced pluripotent stem (iPS) cells are a novel stem cell population induced from mouse and human adult somatic cells through reprogramming by transduction of defined transcription factors. However, detailed differentiation properties and the directional differentiation system of iPS cells have not been demonstrated. Methods and Results-Previously, we established a novel mouse embryonic stem (ES) cell differentiation system that can reproduce the early differentiation processes of cardiovascular cells. We applied our ES cell system to iPS cells and examined directional differentiation of mouse iPS cells to cardiovascular cells. Flk1 (also designated as vascular endothelial growth factor receptor-2)-expressing mesoderm cells were induced from iPS cells after Ϸ4-day culture for differentiation. Purified Flk1 ϩ cells gave rise to endothelial cells and mural cells by addition of vascular endothelial growth factor and serum. Arterial, venous, and lymphatic endothelial cells were also successfully induced. Self-beating cardiomyocytes could be induced from Flk1 ϩ cells by culture on OP9 stroma cells. Time course and efficiency of the differentiation were comparable to those of mouse ES cells. Occasionally, reexpression of transgene mRNAs, including c-myc, was observed in long-term differentiation cultures. Conclusions-Various

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Section: Discussionmentioning

confidence: 99%

Directed and Systematic Differentiation of Cardiovascular Cells From Mouse Induced Pluripotent Stem Cells

et al. 2008

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“…Therefore, ES cells could be feasible as a novel cell source for therapeutic angiogenesis. Recently, we were able to clarify the differentiation process from human ES cells to mature vascular cells (Figure 1) [Sone et al 2007[Sone et al , 2003]. Unlike mouse ES cells, undifferentiated human ES cells already express VEGFR-2, but after differentiation, a VEGFR-2-positive but tumor rejection antigen 1-60 (TRA1-60; undifferentiated marker)-negative population emerged.…”

Section: Es Cell-derived Ecsmentioning

confidence: 99%

“…ES cells are known to exhibit extensive regeneration potential and functional multilineage differentiation capacity, and they are ideal resources for regenerative medicine, which requires large numbers of transplant cells including endothelial cells (ECs) [Yamashita et al 2000]. After the in vitro induction of differentiation in mouse and human ES cells, ECs can be obtained from vascular endothelial growth factor receptor (VEGFR)-2 positive cell fractions [Sone et al 2007[Sone et al , 2003Yamashita et al 2000]. ES-cell-derived ECs express endothelial-specific markers and have been found to form capillary structures in vitro and in vivo [Yamahara et al 2008;Sone et al 2007;Yurugi-Kobayashi et al 2003].…”

Section: Introductionmentioning

confidence: 99%

“…After the in vitro induction of differentiation in mouse and human ES cells, ECs can be obtained from vascular endothelial growth factor receptor (VEGFR)-2 positive cell fractions [Sone et al 2007[Sone et al , 2003Yamashita et al 2000]. ES-cell-derived ECs express endothelial-specific markers and have been found to form capillary structures in vitro and in vivo [Yamahara et al 2008;Sone et al 2007;Yurugi-Kobayashi et al 2003]. In addition, previous studies reported that transplantation of human ES-cellderived ECs accelerated vascular regeneration in mouse hindlimb ischemia [Yamahara et al 2008;Cho et al 2007].…”

Section: Introductionmentioning

confidence: 99%

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Potential use of endothelial progenitor cells for regeneration of the vasculature

Yamahara

Itoh

2009

Therapeutic Advances in Cardiovascular Disease

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Over the past decade, interest has been generated in the study of endothelial progenitor cells (EPCs). EPCs have been studied for their role in endogenous maintenance and for their therapeutic potential in vascular regenerative medicine. Despite their obvious potential in clinical practice, there still remain many controversies regarding how EPCs actually enhance endothelial repair and neovascularization. In addition, because of the limited expansion ability of EPCs, expansion of sufficient EPC populations for therapeutic angiogenesis remains a major task. On the other hand, embryonic stem (ES) cells have an extended self-renewal activity and can be expanded without limit, thus ES-cell-derived endothelial cells could be feasible as a novel cell source for therapeutic angiogenesis. In this review, we discuss recent experimental and clinical findings of EPCs and human ES-cell-derived endothelial cells for the treatment of ischemic cardiovascular diseases.

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“…We previously described the process by which mouse, monkey and human embryonic stem (ES) cells differentiate into vascular cells. 1,2,3 In addition, we used the hindlimb ischemia model with immunodeficient mice to demonstrate that transplanted vascular endothelial cells (ECs) and mural cells (MCs) derived from human (h)ES cells could be successfully incorporated into the host vasculature and significantly accelerate improvements in local blood flow. 3,4 However, immunologic and ethical problems remain to be overcome before clinical application.…”

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Induction and Isolation of Vascular Cells From Human Induced Pluripotent Stem Cells—Brief Report

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Sone

Homma

et al. 2009

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Objective-Induced pluripotent stem (iPS) cells are a novel stem cell population derived from human adult somatic cells through reprogramming using a defined set of transcription factors. Our aim was to determine the features of the directed differentiation of human iPS cells into vascular endothelial cells (ECs) and mural cells (MCs), and to compare that process with human embryonic stem (hES) cells. Methods and Results-We previously established a system for differentiating hES cells into vascular cells. We applied this system to human iPS cells and examined their directed differentiation. After differentiation, TRA1-60 Ϫ Flk1 ϩ cells emerged and divided into VE-cadherin-positive and -negative populations. The former were also positive for CD34, CD31, and eNOS and were consistent with ECs. The latter differentiated into MCs, which expressed smooth muscle ␣-actin and calponin after further differentiation. The efficiency of the differentiation was comparable to that of human ES cells. Conclusions-We succeeded in inducing and isolating human vascular cells from iPS cells and indicate that the properties of human iPS cell differentiation into vascular cells are nearly identical to those of hES cells. This work will contribute to our understanding of human vascular differentiation/development and to the development of vascular regenerative medicine.

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Pathway for Differentiation of Human Embryonic Stem Cells to Vascular Cell Components and Their Potential for Vascular Regeneration

Cited by 132 publications

References 17 publications

Directed and Systematic Differentiation of Cardiovascular Cells From Mouse Induced Pluripotent Stem Cells

Directed and Systematic Differentiation of Cardiovascular Cells From Mouse Induced Pluripotent Stem Cells

Potential use of endothelial progenitor cells for regeneration of the vasculature

Induction and Isolation of Vascular Cells From Human Induced Pluripotent Stem Cells—Brief Report

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