The delayed addition of human mesenchymal stem cells to pre-formed endothelial cell networks results in functional vascularization of a collagen–glycosaminoglycan scaffold in vivo

McFadden, Tara M.; Duffy, Garry P.; Allen, Ashley; Stevens, Hazel Y.; Schwarzmaier, Susanne M.; Plesnila, Nikolaus; Murphy, Mary; Barry, Frank; Guldberg, Robert E.; O’Brien, Fergal J.

doi:10.1016/j.actbio.2013.08.014

Cited by 113 publications

(117 citation statements)

References 67 publications

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“…[4][5][6][7][8]53,77,78 Previous studies have investigated whether prevascularizing 3D constructs in vitro would eradicate this limitation, through the coculture of endothelial stem cells with MSCs [40][41][42][43][79][80][81][82][83] or osteoblasts, 45,84,85 and found that prevascular networks are formed both in vitro and in vivo. Our previous study previously found that rudimentary vessels were formed in vitro when both MSCs and HUVECs were added to the already formed cartilage template.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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In vitro bone regeneration strategies that prime mesenchymal stem cells (MSCs) with chondrogenic factors, to mimic aspects of the endochondral ossification process, have been shown to promote mineralization and vascularization by MSCs both in vitro and when implanted in vivo. However, these approaches required the use of osteogenic supplements, namely dexamethasone, ascorbic acid, and b-glycerophosphate, none of which are endogenous mediators of bone formation in vivo. Rather MSCs, endothelial progenitor cells, and chondrocytes all reside in proximity within the cartilage template and might paracrineally regulate osteogenic differentiation. Thus, this study tests the hypothesis that an in vitro bone regeneration approach that mimics the cellular niche existing during endochondral ossification, through coculture of MSCs, endothelial cells, and chondrocytes, will obviate the need for extraneous osteogenic supplements and provide an alternative strategy to elicit osteogenic differentiation of MSCs and mineral production. The specific objectives of this study were to (1) mimic the cellular niche existing during endochondral ossification and (2) investigate whether osteogenic differentiation could be induced without the use of any external growth factors. To test the hypothesis, we evaluated the mineralization and vessel formation potential of (a) a novel methodology involving both chondrogenic priming and the coculture of human umbilical vein endothelial cells (HUVECs) and MSCs compared with (b) chondrogenic priming of MSCs alone, (c) addition of HUVECs to chondrogenically primed MSC aggregates, (d-f) the same experimental groups cultured in the presence of osteogenic supplements and (g) a noncoculture group cultured in the presence of osteogenic growth factors alone. Biochemical (DNA, alkaline phosphatase [ALP], calcium, CD31 + , vascular endothelial growth factor [VEGF]), histological (alcian blue, alizarin red), and immunohistological (CD31 + ) analyses were conducted to investigate osteogenic differentiation and vascularization at various time points (1, 2, and 3 weeks). The coculture methodology enhanced both osteogenesis and vasculogenesis compared with osteogenic differentiation alone, whereas osteogenic supplements inhibited the osteogenesis and vascularization (ALP, calcium, and VEGF) induced through coculture alone. Taken together, these results suggest that chondrogenic and vascular priming can obviate the need for osteogenic supplements to induce osteogenesis of human MSCs in vitro, while allowing for the formation of rudimentary vessels.

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Section: Discussionmentioning

confidence: 99%

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Freeman

Stevens

Owens

et al. 2016

Tissue Engineering Part A

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show abstract

“…For example, formation of microvasculature is most successful after a delayed addition of MSCs to ECs encapsulated in collagen scaffolds and cocultured in an in vitro environment. 35 This setup emulates the in vivo environment most accurately because MSCs are recruited to the site of vascularization after the ECs have begun the initial formation of nascent microstructures. 35,36 The interaction between ECs and MSCs has been most pronounced in the application of wound healing.…”

Section: Interactions With Ecsmentioning

confidence: 99%

“…35 This setup emulates the in vivo environment most accurately because MSCs are recruited to the site of vascularization after the ECs have begun the initial formation of nascent microstructures. 35,36 The interaction between ECs and MSCs has been most pronounced in the application of wound healing. MSCs near the location of the wound secrete paracrine factors, such as VEGF, to recruit macrophages and ECs, accelerating the wound healing process.…”

Section: Interactions With Ecsmentioning

confidence: 99%

Mesenchymal Stem Cells: Roles and Relationships in Vascularization

Melchiorri

Nguyen

Fisher

2014

Tissue Engineering Part B: Reviews

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“…It is based on the anastomosis between in vitro pre-engineered vessels and those of the host, so that the grafts do not have to rely solely on the host vessel invasion. 40,42 The mechanism, by which this anastomosis occurs between the pre-engineered vessels and the host vasculature, has recently been determined. The pre-engineered vessels surround the nearby host vessels and disrupt the underlying host endothelium, leading to the links between both networks.…”

Section: Discussionmentioning

confidence: 99%

Study of the involvement of allogeneic MSCs in bone formation using the model of transgenic mice

Kuznetsova

Prodanets

Rodimova

et al. 2016

Cell Adhesion & Migration

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Mesenchymal stem cells (MSCs) are thought to be the most attractive type of cells for bone repair. However, much still remains unknown about MSCs and needs to be clarified before this treatment can be widely applied in the clinical practice. The purpose of this study was to establish the involvement of allogeneic MSCs in the bone formation in vivo, using a model of transgenic mice and genetically labeled cells. Polylactide scaffolds with hydroxyapatite obtained by surface selective laser sintering were used. The scaffolds were sterilized and individually seeded with MSCs from the bone marrow of 5-week-old GFP(C) transgenic C57/Bl6 or GFP(¡)C57/Bl6 mice. 4-mm-diameter critical-size defects were created on the calvarial bone of mice using a dental bur. Immediately after the generation of the cranial bone defects, the scaffolds with or without seeded cells were implanted into the injury sites. The cranial bones were harvested at either 6 or 12 weeks after the implantation. GFP(C) transgenic mice having scaffolds with unlabeled MSCs were used for the observation of the host cell migration into the scaffold. GFP(¡) mice having scaffolds with GFP(C) MSCs were used to assess the functioning of the seeded MSCs. The obtained data demonstrated that allogeneic MSCs were found on the scaffolds 6 and 12 weeks post-implantation. By week 12, a newly formed bone tissue from the seeded cells was observed, without an osteogenic predifferentiation. The host cells did not appear, and the control scaffolds without seeded cells remained empty. Besides, a possibility of vessel formation from seeded MSCs was shown, without a preliminary cell cultivation under controlled conditions.

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The delayed addition of human mesenchymal stem cells to pre-formed endothelial cell networks results in functional vascularization of a collagen–glycosaminoglycan scaffold in vivo

Cited by 113 publications

References 67 publications

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Osteogenic Differentiation of Mesenchymal Stem Cells by Mimicking the Cellular Niche of the Endochondral Template

Mesenchymal Stem Cells: Roles and Relationships in Vascularization

Study of the involvement of allogeneic MSCs in bone formation using the model of transgenic mice

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