Effects of Extracellular Matrix Density and Mesenchymal Stem Cells on Neovascularization <i>In Vivo</i>

Kniazeva, Ekaterina; Kachgal, Suraj; Putnam, Andrew J.

doi:10.1089/ten.tea.2010.0275

Cited by 63 publications

(64 citation statements)

References 28 publications

(36 reference statements)

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“…34 There are also a number of studies that have explored the utility of BMSCs co-delivered with ECs to build functional vasculature. 22,25 The results presented here show that all four of the experimental groups (EC-alone, EC-NHLFs, EC-AdSCs, and EC-BMSCs) yielded new human-derived vessels that inosculated with mouse vasculature and perfused the implant with blood. However, functional differences in the capillary networks were also revealed, depending on the identity of the co-delivered stromal cells.…”

Section: Discussionmentioning

confidence: 74%

“…Fibrin is a naturally occurring biopolymer that acts as the provisional matrix during wound healing in the human body, and has been widely shown in the literature to support neovascularization. 22,33,35,39,40 The animal model used here has also been widely exploited in the literature to approximate wound healing and test the ability of transplanted human cells to form vasculature, 19,22,29,[33][34][35] in part because the human cells injected into SCID mice are not rejected.…”

Section: Discussionmentioning

confidence: 99%

“…hCD31, alpha-smooth muscle actin (a-SMA), and calponin were immunohistochemically stained in our laboratory on unstained serial sections provided by AML. Paraffin sections were rehydrated according to a standard protocol 22 and then steamed in a vegetable steamer for 25 min in an antigen retrieval solution (Dako). Slides were equilibrated in TBS-T, and then a DakoEnVision System-HRP (DAB) kit (Dako) was used for all subsequent staining.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…19,20 In the case of engineered capillary networks, our laboratory and many others have had some previous success in inducing capillary growth in both 3D in vitro cultures, 21 and in vivo subcutaneous implants. 22 The results from such studies have led to the consensus that co-delivery of ECs and a secondary mesenchymal cell type produces the necessary cues to induce tubular sprouting of ECs, and stromal cell differentiation toward a pericytic phenotype. 23 Despite the consensus of this paradigm, there is virtually no consensus with respect to the choice of cells to co-deliver with ECs.…”

Section: Introductionmentioning

confidence: 99%

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Stromal Cell Identity Influences the In Vivo Functionality of Engineered Capillary Networks Formed by Co-delivery of Endothelial Cells and Stromal Cells

Grainger

Carrion

Ceccarelli

et al. 2013

Tissue Engineering Part A

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A major translational challenge in the fields of therapeutic angiogenesis and tissue engineering is the ability to form functional networks of blood vessels. Cell-based strategies to promote neovascularization have been widely explored, and have led to the consensus that co-delivery of endothelial cells (ECs) (or their progenitors) with some sort of a supporting stromal cell type is the most effective approach. However, the choice of stromal cells has varied widely across studies, and their impact on the functional qualities of the capillaries produced has not been examined. In this study, we injected human umbilical vein ECs alone or with normal human lung fibroblasts (NHLFs), human bone marrow-derived mesenchymal stem cells (BMSCs), or human adipose-derived stem cells (AdSCs) in a fibrin matrix into subcutaneous pockets in SCID mice. All conditions yielded new human-derived vessels that inosculated with mouse vasculature and perfused the implant, but there were significant functional differences in the capillary networks, depending heavily on the identity of the co-delivered stromal cells. EC-alone and EC-NHLF implants yielded immature capillary beds characterized by high levels of erythrocyte pooling in the surrounding matrix. EC-BMSC and EC-AdSC implants produced more mature capillaries characterized by less extravascular leakage and the expression of mature pericyte markers. Injection of a fluorescent tracer into the circulation also showed that EC-BMSC and EC-AdSC implants formed vasculature with more tightly regulated permeability. These results suggest that the identity of the stromal cells is key to controlling the functional properties of engineered capillary networks.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Stromal Cell Identity Influences the In Vivo Functionality of Engineered Capillary Networks Formed by Co-delivery of Endothelial Cells and Stromal Cells

Grainger

Carrion

Ceccarelli

et al. 2013

Tissue Engineering Part A

Self Cite

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“…In addition to chemical factors, mechanical forces also control angiogenesis 23,37 . The stiffness of fibrin gel changes in a fibrinogen concentration-dependent manner 57 and manipulating the fibrinogen concentration may affect angiogenesis not only through chemical signals but also through physical cues 58,59 . Therefore, physicochemical properties of the fibrin gels may need to be optimized carefully to recapitulate physiological organ-specific angiogenesis in the future.…”

Section: Discussionmentioning

confidence: 99%

Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis

Mammoto

2014

JoVE

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Recent significant advances in stem cell research and bioengineering techniques have made great progress in utilizing biomaterials to regenerate and repair damage in simple tissues in the orthopedic and periodontal fields. However, attempts to regenerate the structures and functions of more complex three-dimensional (3D) organs such as lungs have not been very successful because the biological processes of organ regeneration have not been well explored. It is becoming clear that angiogenesis, the formation of new blood vessels, plays key roles in organ regeneration. Newly formed vasculatures not only deliver oxygen, nutrients and various cell components that are required for organ regeneration but also provide instructive signals to the regenerating local tissues. Therefore, to successfully regenerate lungs in an adult, it is necessary to recapitulate the lung-specific microenvironments in which angiogenesis drives regeneration of local lung tissues. Although conventional in vivo angiogenesis assays, such as subcutaneous implantation of extracellular matrix (ECM)-rich hydrogels (e.g., fibrin or collagen gels or Matrigel -ECM protein mixture secreted by Engelbreth-Holm-Swarm mouse sarcoma cells), are extensively utilized to explore the general mechanisms of angiogenesis, lung-specific angiogenesis has not been well characterized because methods for orthotopic implantation of biomaterials in the lung have not been well established. The goal of this protocol is to introduce a unique method to implant fibrin gel on the lung surface of living adult mouse, allowing for the successful recapitulation of host lung-derived angiogenesis inside the gel. This approach enables researchers to explore the mechanisms by which the lung-specific microenvironment controls angiogenesis and alveolar regeneration in both normal and pathological conditions. Since implanted biomaterials release and supply physical and chemical signals to adjacent lung tissues, implantation of these biomaterials on diseased lung can potentially normalize the adjacent diseased tissues, enabling researchers to develop new therapeutic approaches for various types of lung diseases. Video LinkThe video component of this article can be found at

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Fabrication of multi‐well chips for spheroid cultures and implantable constructs through rapid prototyping techniques

Lopa

Piraino

Kemp

et al. 2015

Biotech & Bioengineering

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1"Three-dimensional culture models, such as cell spheroids, are widely used in basic and translational 2" research. Since handling a high number of cell spheroids is more complex and time consuming than 3"handling monolayer cultures, we exploited laser ablation and replica molding to fabricate 4" polydimethylsiloxane (PDMS) multi-well chips for the generation and culture of multiple cell 5"spheroids. Articular chondrocytes (ACs) were used to validate the multi-well PDMS chips. Multi-6" well spheroids were comparable or superior to standard spheroids in terms of chondrogenic 7" differentiation. Moreover, the use of multi-well chips significantly reduced the operation time for 8" cell seeding and medium refresh. 9"Using a similar approach, clinical-grade fibrin was used to generate implantable multi-well 10"constructs, allowing differential cell seeding in the construct structure and in the wells. Multi-well 11"fibrin constructs with high cell density regions were compared with constructs where ACs were 12" homogeneously distributed. Expression of chondrogenic genes was increased after 7 days in vitro in regions can be precisely generated in multi-well constructs and that they are still detectable after 5 16" weeks in vivo. 17"In conclusion, multi-well chips for the generation and culture of multiple cell spheroids can be 18" fabricated by low-cost rapid prototyping techniques. Furthermore, these techniques can be used to 19"generate implantable constructs with defined architecture and spatially controlled cell distribution, 20"allowing the in vitro and in vivo investigation of cell interactions in a 3D environment.

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Effects of Extracellular Matrix Density and Mesenchymal Stem Cells on Neovascularization In Vivo

Cited by 63 publications

References 28 publications

Stromal Cell Identity Influences the In Vivo Functionality of Engineered Capillary Networks Formed by Co-delivery of Endothelial Cells and Stromal Cells

Stromal Cell Identity Influences the In Vivo Functionality of Engineered Capillary Networks Formed by Co-delivery of Endothelial Cells and Stromal Cells

Implantation of Fibrin Gel on Mouse Lung to Study Lung-specific Angiogenesis

Fabrication of multi‐well chips for spheroid cultures and implantable constructs through rapid prototyping techniques

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