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Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo

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Abstract

We describe the differentiation of human embryonic stem (hES) cells into endothelial cells using a scalable two-dimensional method that avoids an embryoid-body intermediate. After transplantation into severe combined immunodeficient (SCID) mice, the differentiated cells contributed to arborized blood vessels that integrated into the host circulatory system and served as blood conduits for 150 d.

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Figure 1: Generation of hES cell–derived CD34+ cells.
Figure 2: hES cell–derived endothelial cells form functional vessels in vivo.

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Acknowledgements

This study was partially supported by National Institutes of Health grants K01DK064696 (Z.W.), P20RR018789 (Z.W.), P01CA80124 (R.K.J., D.F.), R01CA96915 (D.F.) and R01CA115767 (R.K.J.) and the Harvard Stem Cell Institute.

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Author notes

  1. Zack Z Wang, Patrick Au and Tong Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Maine Medical Center Research Institute, Scarborough, 04074, Maine, USA

    Zack Z Wang, Hao Bai & Melanie Arzigian

  2. Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Zack Z Wang, Tong Chen, Ying Shao, Laurence M Daheron & David T Scadden

  3. Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.,

    Patrick Au, Dai Fukumura & Rakesh K Jain

  4. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Patrick Au

  5. Department of Hematology, Shanghai Huashan Hospital, Fudan University, Shanghai, 200040, China

    Tong Chen

  6. Harvard Stem Cell Institute, Cambridge, 02138, Massachusetts, USA

    Laurence M Daheron & David T Scadden

Authors
  1. Zack Z Wang
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  2. Patrick Au
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  3. Tong Chen
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  4. Ying Shao
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  5. Laurence M Daheron
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  6. Hao Bai
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  7. Melanie Arzigian
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  8. Dai Fukumura
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  9. Rakesh K Jain
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  10. David T Scadden
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Contributions

Z.Z.W. designed, coordinated and performed research, analyzed data and wrote the manuscript; P.A. and T.C. performed research, analyzed data and wrote the manuscript; Y.S., L.M.D., H.B., M.A. performed research; D.F. provided useful discussions and wrote the manuscript; R.K.J. and D.T.S. designed and coordinated research, analyzed data and wrote the manuscript.

Corresponding authors

Correspondence to Zack Z Wang, Rakesh K Jain or David T Scadden.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Schematic representation of hESC culture. (PDF 108 kb)

Supplementary Fig. 2

RT-PCR analysis of CD31 and GATA-2 gene expression. (PDF 59 kb)

Supplementary Fig. 3

FACS analysis of CD34+ cells after magnetic bead selection. (PDF 58 kb)

Supplementary Fig. 4

Differentiation of hESCs with three batches of FBS. (PDF 79 kb)

Supplementary Fig. 5

Differentiation of hESCs in serum-free media. (PDF 62 kb)

Supplementary Fig. 6

Cell number of adherent and suspension cells. (PDF 50 kb)

Supplementary Fig. 7

Hematopoietic differentiation of hESC-derived CD34+ cells. (PDF 75 kb)

Supplementary Fig. 8

Gene expression analysis of hESC-derived endothelial cells by RT-PCR. (PDF 256 kb)

Supplementary Video 1

Blood flow in HESC-derived engineered vessels. (MOV 719 kb)

Supplementary Video 2

Three-dimensional image of HESC-derived engineered vessels and extracellular matrix. (MOV 283 kb)

Supplementary Methods (DOC 100 kb)

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Wang, Z., Au, P., Chen, T. et al. Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nat Biotechnol 25, 317–318 (2007). https://doi.org/10.1038/nbt1287

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  • DOI: https://doi.org/10.1038/nbt1287

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