Evaluation of Endothelial Cells Differentiated from Amniotic Fluid-Derived Stem Cells

Benavides, Omar M.; Petsche, Jennifer; Moise, Kenneth J.; Johnson, Anthony J.; Jacot, Jeffrey G.

doi:10.1089/ten.tea.2011.0392

Cited by 44 publications

(62 citation statements)

References 30 publications

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“…[26][27][28][29][30] Alternatively, broad potential for differentiation and high proliferation rates make AFSC well suited for use in regenerative medicine therapies such as engineered skeletal/cardiac muscles, tendons, heart valves, and blood vessels. 11,17,[31][32][33][34][35] This study confirms our previous work on the capacity for VEGF-mediated differentiation of c-kit + AFSC into endothelial-like cells, 14 as well as illustrates the vasculogenic and perivasculogenic potential of AFSC within a threedimensional fibrin/PEG scaffold in vitro.…”

Section: Discussionsupporting

confidence: 86%

“…11,14,36 The subpopulation of CD31 + cells within these c-kit-sorted AFSC is minor ( < 0.25%), but warrants further investigation to determine the degree of endothelial enrichment compared to endothelial differentiation. Recent studies suggest that 1 mL of human AF contains *10 4 cells, 80% of which are viable, and 1% of which are c-kit + .…”

Section: Discussionmentioning

confidence: 97%

“…11 AFSC could also prove to be a significant source for autologous therapies in neonates such as in an engineered cardiovascular patch for Tetralogy of Fallot repair 12 or to aid in vascular reconstruction of other congenital defects. 13 AFSC isolated and differentiated into endothelial cells in previous studies from our group express key endothelial molecular markers (vWF, eNOS, and CD31), display functional phenotypes associated with endothelial cells (nitric oxide production and ac-LDL uptake), and form networks when encapsulated in Matrigel, 14 all of which suggest vasculogenic potential. In addition, AFSC have a similar morphology, surface marker expression, and differentiation capacity compared to MSC, a proven source of perivascular cells, suggesting the potential use of AFSC as a vascular support cell source.…”

Section: Introductionmentioning

confidence: 93%

“…In addition, AFSC have a similar morphology, surface marker expression, and differentiation capacity compared to MSC, a proven source of perivascular cells, suggesting the potential use of AFSC as a vascular support cell source. 11,[14][15][16][17] Fibrin-based hydrogels stimulate vascularization and are used in clinical applications, such as growth factor delivery and cell encapsulation, making them an appropriate platform for assessing the vasculogenic potential of AFSC. 18 The main limitation associated with fibrin in tissue engineering is rapid degradation, which leads to loss of implant volume within days.…”

Section: Introductionmentioning

confidence: 99%

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Capillary-Like Network Formation by Human Amniotic Fluid-Derived Stem Cells Within Fibrin/Poly(Ethylene Glycol) Hydrogels

Benavides

Quinn

Pok

et al. 2015

Tissue Engineering Part A

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A major limitation in tissue engineering strategies for congenital birth defects is the inability to provide a significant source of oxygen, nutrient, and waste transport in an avascular scaffold. Successful vascularization requires a reliable method to generate vascular cells and a scaffold capable of supporting vessel formation. The broad potential for differentiation, high proliferation rates, and autologous availability for neonatal surgeries make amniotic fluid-derived stem cells (AFSC) well suited for regenerative medicine strategies. AFSC-derived endothelial cells (AFSC-EC) express key proteins and functional phenotypes associated with endothelial cells. Fibrin-based hydrogels were shown to stimulate AFSC-derived network formation in vitro but were limited by rapid degradation. Incorporation of poly(ethylene glycol) (PEG) provided mechanical stability (65% -9% weight retention vs. 0% for fibrin-only at day 14) while retaining key benefits of fibrin-based scaffolds-quick formation (10 -3 s), biocompatibility (88% -5% viability), and vasculogenic stimulation. To determine the feasibility of AFSC-derived microvasculature, we compared AFSC-EC as a vascular cell source and AFSC as a perivascular cell source to established sources of these cell types-human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), respectively. Cocultures were seeded at a 4:1 endothelial-toperivascular cell ratio, and gels were incubated at 37°C for 2 weeks. Mechanical testing was performed using a stress-controlled rheometer (G¢ = 95 -10 Pa), and cell-seeded hydrogels were assessed based on morphology. Network formation was analyzed based on key parameters such as vessel thickness, length, and area, as well as the degree of branching. There was no statistical difference between individual cultures of AFSC-EC and HUVEC in regard to these parameters, suggesting the vasculogenic potential of AFSC-EC; however, the development of robust vessels required the presence of both an endothelial and a perivascular cell source and was seen in AFSC cocultures (70% -20% vessel length, 90% -10% vessel area, and 105% -10% vessel thickness compared to HUVEC/MSC). At a fixed seeding density, the coculture of AFSC with AFSC-EC resulted in a synergistic effect on network parameters similar to MSC (150% vessel length, 147% vessel area, 150% vessel thickness, and 155% branching). These results suggest that AFSC-EC and AFSC have significant vasculogenic and perivasculogenic potential, respectively, and are suited for in vivo evaluation.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Capillary-Like Network Formation by Human Amniotic Fluid-Derived Stem Cells Within Fibrin/Poly(Ethylene Glycol) Hydrogels

Benavides

Quinn

Pok

et al. 2015

Tissue Engineering Part A

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“…[19][20][21] F o r P e e r R e v i e w 4 One potential source of both endothelial and perivascular cell types is amniotic fluidderived stem cells (AFSC). [22][23][24] Previous results from our lab suggest that AFSC in threedimensional co-cultures act as a perivascular support cell source similar to MSC and that AFSCderived endothelial cells (AFSC-EC) promote vascular network formation similar to mature endothelial cell. [25] Significant advantages to using AFSC in regenerative medicine strategies include broad differentiation capacity, rapid proliferation, and the potential for use in autologous therapies in neonates, such as an engineered cardiovascular patch for repair of congenital heart defects.…”

mentioning

confidence: 99%

In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid‐derived stem cells

Benavides

Brooks

Cho

et al. 2015

J Biomedical Materials Res

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One of the greatest challenges in regenerative medicine is generating clinically-relevant engineered tissues with functional blood vessels. Vascularization is a key hurdle faced in designing tissue constructs larger than the in vivo limit of oxygen diffusion. In this study, we utilized fibrin-based hydrogels as a foundation for vascular formation, poly(ethylene glycol) (PEG) to modify fibrinogen and increase scaffold longevity, and human amniotic fluid-derived stem cells (AFSC) as a source of vascular cell types (AFSC-EC). AFSC hold great potential for use in regenerative medicine strategies, especially those involving autologus congenital applications, and we have shown previously that AFSC-seeded fibrin-PEG hydrogels have the potential to form three-dimensional vascular-like networks in vitro. We hypothesized that subcutaneously injecting these hydrogels in immunodeficient mice would both induce a fibrindriven angiogenic host response and promote in situ AFSC-derived neovascularization. Two weeks post-injection, the average maximum invasion distance of host murine cells into the subcutaneous fibrin/PEG scaffold was 147±90µm after one week and 395±138µm after two weeks, the average number of cell-lined lumen per mm 2 was significantly higher in hydrogels

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Stimulation of Therapeutic Angiogenesis Using Amniotic Fluid Stem Cells

Mirabella

2014

Perinatal Stem Cells

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Evaluation of Endothelial Cells Differentiated from Amniotic Fluid-Derived Stem Cells

Cited by 44 publications

References 30 publications

Capillary-Like Network Formation by Human Amniotic Fluid-Derived Stem Cells Within Fibrin/Poly(Ethylene Glycol) Hydrogels

Capillary-Like Network Formation by Human Amniotic Fluid-Derived Stem Cells Within Fibrin/Poly(Ethylene Glycol) Hydrogels

In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid‐derived stem cells

Stimulation of Therapeutic Angiogenesis Using Amniotic Fluid Stem Cells

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