Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels

Au, Patrick; Dahéron, Laurence; Duda, Dan G.; Cohen, Kenneth S.; Tyrrell, James; Lanning, Ryan M.; Fukumura, Dai; Scadden, David T.; Jain, Rakesh K.

doi:10.1182/blood-2007-06-094318

Cited by 319 publications

(285 citation statements)

References 14 publications

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“…3A-D). In agreement with previous observations (22,25,26), when constructs with HUVECs alone were implanted, circular structures formed by day 4 after implantation, but the engineered vessels appeared counterfeit, remained immature, and eventually regressed. Implanted constructs generally showed relative behavior similar to in vitro culture, with endothelial-only scaffolds showing poor survival and marginal lumen formation and no evidence of anastomosis.…”

Section: Formation Of Engineered Vessels Within the 3d Porous Scaffolsupporting

confidence: 78%

Engineered vascularized bone grafts

Tsigkou

Pomerantseva²,

Spencer

et al. 2010

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

210

184

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Clinical protocols utilize bone marrow to seed synthetic and decellularized allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow-derived cytokines induce host neovascularization at the graft surface, but hypoxic conditions cause cell death at the core. Addition of cellular components that generate an extensive primitive plexus-like vascular network that would perfuse the entire scaffold upon anastomosis could potentially yield significantly higher-quality grafts. We used a mouse model to develop a two-stage protocol for generating vascularized bone grafts using mesenchymal stem cells (hMSCs) from human bone marrow and umbilical cord-derived endothelial cells. The endothelial cells formed tube-like structures and subsequently networks throughout the bone scaffold 4–7 days after implantation. hMSCs were essential for stable vasculature both in vitro and in vivo; however, contrary to expectations, vasculature derived from hMSCs briefly cultured in medium designed to maintain a proliferative, nondifferentiated state was more extensive and stable than that with hMSCs with a TGF-β-induced smooth muscle cell phenotype. Anastomosis occurred by day 11, with most hMSCs associating closely with the network. Although initially immature and highly permeable, at 4 weeks the network was mature. Initiation of scaffold mineralization had also occurred by this period. Some human-derived vessels were still present at 5 months, but the majority of the graft vasculature had been functionally remodeled with host cells. In conclusion, clinically relevant progenitor sources for pericytes and endothelial cells can serve to generate highly functional microvascular networks for tissue engineered bone grafts.

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Section: Formation Of Engineered Vessels Within the 3d Porous Scaffolsupporting

confidence: 78%

Engineered vascularized bone grafts

Tsigkou

Pomerantseva²,

Spencer

et al. 2010

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

210

184

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“…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%

“…S9) with 10T1/2 MPCs in vivo using the tissue-engineered model in the cranial window of SCID mice (26,27). We found that T1D-iPS cell-derived ECs could generate a functional vasculature within 2 wk of coimplantation.…”

mentioning

confidence: 98%

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

140

112

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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.

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“…Many studies have verified the ability of MSCs in supporting the long-term survival and stability of endothelial cells [16], [17] when they are co-cultured in the same niche. Stable and functional blood vessel network can be regenerated in vivo by injecting mixed mesenchymal precursor cells and HUVECs, whereas tubular network formed by HUVECs alone tend to regress and disappear over time [12].…”

Section: B Cell Morphologymentioning

confidence: 99%

Endothelialization of Acellular Porcine ECM with Chemical Modification

Wang¹,

Bronshtein²,

Sarig³

et al. 2012

IJBBB

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Abstract-Vascularization remains a critical requirement for the long term survival of engineered tissue constructs, especially thick ones. Such thick constructs for cardiac tissue engineering has been reported by our group and others based on decellularized porcine cardiac extracellular matrix (pcECM) that has been shown to resemble the native tissue both structurally and chemically. The network of inherent vasculature, which was largely retained within our pcECM, can be used as primers for re-endothelialization and neo-vascularization with regenerative cells. Endothelial cells alone, seeded onto the ECM, not only attached and survived but also rearranged into typical confluent monolayer with self-alignment. Sequential co-cultures of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC) were shown to support the growth of both lineages on the surface and in the vasculature of reseeded pcECM. After ECM treatment with gelatin or fibronectin, cell proliferation increased significantly for both MSCs and HUVECs. Preliminary results showed that future efforts combining co-culture, treated scaffolds and dynamic culture environment may result in re-endothelialization leading to functional blood vessels in thick engineered tissue for partial cardiac replacement therapy.

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Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels

Cited by 319 publications

References 14 publications

Engineered vascularized bone grafts

Engineered vascularized bone grafts

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

Endothelialization of Acellular Porcine ECM with Chemical Modification

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