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

Wang, Zack Z.; Au, Patrick; Chen, Tong; Shao, Ying; Dahéron, Laurence; Bai, Hao; Arzigian, Melanie; Fukumura, Dai; Jain, Rakesh K.; Scadden, David T.

doi:10.1038/nbt1287

Cited by 273 publications

(260 citation statements)

References 13 publications

Supporting

Mentioning

246

Contrasting

Unclassified

Order By: Relevance

“…Although various 3D culture systems (e.g., embryoid bodies) have been proposed for efficient generation of ECs (8), we found that a 2D approach is far more efficient than a 3D method for EC derivation from hESCs (20). However, the superiority of 2D culture was not known for iPS-EC differentiation.…”

Section: Discussionmentioning

confidence: 87%

“…We previously reported successful generation of durable engineered blood vessels in vivo using HUVECs (19) or ECs derived from cord blood-derived EPCs (26) or hESCs (20). In all cases, coimplantation with murine MPC 10T1/2 cells (19,20,26) or human MSCs (29) was required to sustain these engineered blood vessels in vivo. Translation of our previous findings will thus require patientcompatible sources of both ECs and mesenchymal cells in a large quantity.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the vasculogenic potential of different stem cell lines appears to be much more variable for hiPS cells than for hESCs, and this could have a direct impact on differentiation capability (31). We have previously reported on a recently developed 2D approach of deriving ECs from hESCs using CD34 sorting, implicating CD34 as a primitive EPC marker (20). CD34 + progenitor cells from peripheral blood appear to be a popular starting material from which to derive hiPS cells (32).…”

Section: Discussionmentioning

confidence: 99%

“…CD34 + progenitor cells from peripheral blood appear to be a popular starting material from which to derive hiPS cells (32). We used magnetic bead sorting to obtain up to 6% CD34 + cells using the healthy hiPS cell lines (SI Appendix, Table S1), and we used endothelial differentiation culture conditions as described for hESCs (20). In our experience, the hiPS-ECs derived from CD34 + cells were unable to expand further in culture.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, we tested whether hiPS cells derived from patients harboring diseases with potential vascular complications, such as type 1 diabetes (T1D), We first established a robust protocol for EPC derivation. The previously established method for EC differentiation from hESCs using CD34 sorting (20) was not optimal for hiPS cells (SI Appendix, Table S1). Thus, we sorted the CD34 + cell subpopulation coexpressing the early EPC markers neuropilin 1 (NRP1) (21) and VEGF receptor 2, human kinase insert domaincontaining receptor (KDR) (22).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells

Samuel

Dahéron

Liao

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

139

112

View full text Add to dashboard Cite

Fig. 2. Rapid induction of interchromosomal interactions by nuclear hormone signaling. (A) 3D-FISH confirmation of E 2 -induced (60 min) TFF1:GREB1 interchromosomal interactions in HMECs with the distribution of loci distances measured (box plot with scatter plot) and quantification of colocalization (bar graph) before and after E 2 treatment. Cells exhibiting mono-or biallelic interactions were combined for comparison with cells showing no colocalization; statistical significance in the bar graph was determined by χ 2 test (**, P < 0.001). (B) 2D FISH confirmation of the interchromosomal interactions in HMEC cells by combining chromosome paint (aqua) and specific DNA probes (green and red). (Upper) Illustrates two examples of mock-treated cells. (Lower) Shows the biallelic interactions/ nuclear reorganization after E 2 treatment for 60 min, exhibiting kissing events between chromosome 21 and chromosome 2. (C) Similar analysis on HMECs, but in this case using 3D FISH to paint chromosome 2 (red) and chromosome 21 (green), showing E 2 -induced chromosome 2-chromosome 21 interaction. Both assays revealed neither chromosome 21-chromosome 21 nor chromosome 2-chromosome 2 interactions in response to E 2. (D) Temporal kinetics of GREB1:TFF1 interactions by 3D FISH in HMECs (**, P < 0.001 by χ 2 ). (E-G) Nuclear microinjection of siRNA against ERα, CBP/p300, or SRC1/pCIP prevented E 2 -induced interchromosomal interactions, counting both mono-and biallelic interactions (**, P < 0.001 by χ 2 ). The injection of siER and siDLC1 were done in the same experiment, sharing the same control group. (H) Nuclear microinjection of siRNA against LSD1, which was shown to be required for estrogen-induced gene expression (22), did not block E 2 -induced interchromosomal interactions. The injection of siLSD1 and SRC1/pCIP were done in a single experiment, sharing the same control group.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells

Samuel

Dahéron

Liao

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

139

112

View full text Add to dashboard Cite

show abstract

Endothelial Differentiation of Embryonic Stem Cells

Blancas

Lauer

McCloskey

2008

CP Stem Cell Biology

View full text Add to dashboard Cite

Vascular progenitor cells derived from stem cells could potentially lead to a variety of clinically relevant applications, including cell‐based therapies and tissue engineering. Here, we describe methods for isolating purified proliferating populations of vascular endothelial cells from mouse embryonic stem cells (mESC) using Flk‐1 positive sorted cells, VEGF supplementation, and a rigorous manual selection technique required for endothelial cell purification and expansion. Using this in vitro derivation procedure, it is possible to obtain millions of cells at various stages of differentiation, with the potential for up to 25 population doublings. Curr. Protoc. Stem Cell Biol. 6:1F.5.1‐1F.5.19. © 2008 by John Wiley & Sons, Inc.

show abstract

Lentiviral Transduction and Clonal Selection of hESCs with Endothelial‐Specific Transgenic Reporters

James

Kloss

Zaninović

et al. 2011

CP Stem Cell Biology

View full text Add to dashboard Cite

Generation of vascular endothelial cells (EC) from human embryonic stem cells (hESC) is a vital component of cell‐based strategies for treatment of cardiovascular disease. Before hESC‐derived ECs can be administered in therapeutic modalities, however, chemically defined culture conditions must be developed that reproducibly and robustly induce vascular differentiation. One approach to screening for culture conditions that support differentiation of hESCs to any cell type is their genetic modification with exogenous DNA sequence comprising a tissue‐specific gene promoter driving reporters such as fluorescent protein or antibiotic drug resistance. The protocols herein provide instructions for the generation of clonal hESC lines containing a reporter transgene that is specifically expressed in vascular endothelial derivatives. Additionally, they demonstrate the methodology employed to assess vascular differentiation from clonal lines. Together, these protocols provide a solid foundation for study of vascular differentiation, and may also be applied, in principle, to studies of other specialized cell types derived from hESCs. Curr. Protoc. Stem Cell Biol. 17:1F.12.1‐1F.12.14. © 2011 by John Wiley & Sons, Inc.

show abstract

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

Cited by 273 publications

References 13 publications

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells

Generation of functionally competent and durable engineered blood vessels from human induced pluripotent stem cells

Endothelial Differentiation of Embryonic Stem Cells

Lentiviral Transduction and Clonal Selection of hESCs with Endothelial‐Specific Transgenic Reporters

Contact Info

Product

Resources

About