Engineering Robust and Functional Vascular Networks In Vivo With Human Adult and Cord Blood–Derived Progenitor Cells

Melero‐Martin, Juan M.; Obaldia, Maria Elena De; Kang, Soo Young; Khan, Zia A.; Yuan, Lei; Oettgen, Peter; Bischoff, Joyce

doi:10.1161/circresaha.108.178590

Cited by 446 publications

(530 citation statements)

References 41 publications

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“…Furthermore, it is suggested that 10T1/2 cells differentiate into SMCs or pericytes through heterotypic interactions with ECs (23,24,26). Recently, the perivascular/pericyte origin of bone marrow MSCs (32,33) has been identified, and the ability of these cells to differentiate to SMCs and stabilize nascent blood vessels (22,34,35) is being characterized.…”

Section: Discussionmentioning

confidence: 99%

Engineered vascularized bone grafts

Tsigkou

Pomerantseva²,

Spencer

et al. 2010

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

206

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: Discussionmentioning

confidence: 99%

Engineered vascularized bone grafts

Tsigkou

Pomerantseva²,

Spencer

et al. 2010

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

206

184

View full text Add to dashboard Cite

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“…Compared with mature endothelial cells that possess limited regenerative capacity 46 , ECFCs are endowed with high proliferative potential and robust vasculogenic properties that render these cells a promising opportunity for clinical use 47 . Our pre-clinical approach allowed ECFCs-MFSD2A to increase in situ EpDPE production, which in turn showed inhibitory effects on angiogenesis, vascular permeability and expression of inflammatory cytokines, thus leading to the clinical amelioration of intestinal inflammation ( Figure 7B).…”

Section: Discussionmentioning

confidence: 99%

MFSD2A Promotes Endothelial Generation of Inflammation-Resolving Lipid Mediators and Reduces Colitis in Mice

et al. 2017

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“…Several groups have cocultured putative EPC with MSC or osteoblast-like cell types on the premise that this strategy will generate prevascular networks within bone tissue-engineered grafts to aid bone repair [13][14][15][16][17][18]. However, the majority of studies used ECs [19][20][21][22][23] rather than ECFC.…”

Section: Discussionmentioning

confidence: 99%

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

et al. 2012

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Umbilical cord blood‐derived endothelial colony‐forming cells (UCB‐ECFC) show utility in neovascularization, but their contribution to osteogenesis has not been defined. Cocultures of UCB‐ECFC with human fetal‐mesenchymal stem cells (hfMSC) resulted in earlier induction of alkaline phosphatase (ALP) (Day 7 vs. 10) and increased mineralization (1.9×; p < .001) compared to hfMSC monocultures. This effect was mediated through soluble factors in ECFC‐conditioned media, leading to 1.8–2.2× higher ALP levels and a 1.4–1.5× increase in calcium deposition (p < .01) in a dose‐dependent manner. Transcriptomic and protein array studies demonstrated high basal levels of osteogenic (BMPs and TGF‐βs) and angiogenic (VEGF and angiopoietins) regulators. Comparison of defined UCB and adult peripheral blood ECFC showed higher osteogenic and angiogenic gene expression in UCB‐ECFC. Subcutaneous implantation of UCB‐ECFC with hfMSC in immunodeficient mice resulted in the formation of chimeric human vessels, with a 2.2‐fold increase in host neovascularization compared to hfMSC‐only implants (p = .001). We conclude that this study shows that UCB‐ECFC have potential in therapeutic angiogenesis and osteogenic applications in conjunction with MSC. We speculate that UCB‐ECFC play an important role in skeletal and vascular development during perinatal development but less so in later life when expression of key osteogenesis and angiogenesis genes in ECFC is lower. Stem Cells2012;30:1911–1924

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Engineering Robust and Functional Vascular Networks In Vivo With Human Adult and Cord Blood–Derived Progenitor Cells

Cited by 446 publications

References 41 publications

Engineered vascularized bone grafts

Engineered vascularized bone grafts

MFSD2A Promotes Endothelial Generation of Inflammation-Resolving Lipid Mediators and Reduces Colitis in Mice

Vasculogenic and Osteogenesis-Enhancing Potential of Human Umbilical Cord Blood Endothelial Colony-Forming Cells

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