Fate of Bone Marrow Stromal Cells in a Syngenic Model of Bone Formation

Boukhechba, Florian; Balaguer, Thierry; Bouvet-Gerbettaz, Sébastien; Michiels, Jean‐François; Bouler, Jean‐Michel; Carle, Georges F.; Scimeca, Jean‐Claude; Rochet, Nathalie

doi:10.1089/ten.tea.2010.0461

Cited by 31 publications

(24 citation statements)

References 48 publications

(73 reference statements)

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“…Cells were shown to survive at least two weeks in vivo , but with a decreasing bioluminescent signal after one week. This has been supported in a similar subcutaneous model, as applied in the present work, where implanted MSCs did not survive more than three weeks after implantation [30]. Without perivascular cells, vascular maturation is impaired leading to an endothelium prone to regression [10,11].…”

Section: Discussionsupporting

confidence: 71%

Mesenchymal stem cells induce endothelial cell quiescence and promote capillary formation

et al. 2014

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IntroductionRapid establishment of functional blood vessels is a prerequisite for successful tissue engineering. During vascular development, endothelial cells (ECs) and perivascular cells assemble into a complex regulating proliferation of ECs, vessel diameter and production of extracellular matrix proteins. The aim of this study was to evaluate the ability of mesenchymal stem cells (MSCs) to establish an endothelial-perivascular complex in tissue-engineered constructs comprising ECs and MSCs.MethodsPrimary human ECs and MSCs were seeded onto poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) scaffolds and grown in dynamic culture before subcutaneous implantation in immunocompromised mice for 1 and 3 weeks. Cellular activity, angiogenic stimulation and vascular assembly in cell/scaffold constructs seeded with ECs or ECs/MSCs in a 5:1 ratio was monitored with real-time RT-PCR, ELISA and immunohistochemical microscopy analysis.ResultsA quiescent phenotype of ECs was generated, by adding MSCs to the culture system. Decreased proliferation of ECs, in addition to up-regulation of selected markers for vascular maturation was demonstrated. Baseline expression of VEGFa was higher for MSCs compared with EC (P <0.001), with subsequent up-regulated VEGFa-expression for EC/MSC constructs before (P <0.05) and after implantation (P <0.01). Furthermore, an inflammatory response with CD11b + cells was generated from implantation of human cells. At the end of the 3 week experimental period, a higher vascular density was shown for both cellular constructs compared with empty control scaffolds (P <0.01), with the highest density of capillaries being generated in constructs comprising both ECs and MSCs.ConclusionsInduction of a quiescent phenotype of ECs associated with vascular maturation can be achieved by co-seeding with MSCs. Hence, MSCs can be appropriate perivascular cells for tissue-engineered constructs.

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Section: Discussionsupporting

confidence: 71%

Mesenchymal stem cells induce endothelial cell quiescence and promote capillary formation

et al. 2014

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“…The lack of bone formation could also be related to the death of implanted cells. Indeed, converging data have recently reported that grafted MSC do not survive more than 3 weeks, notably after subcutaneous implantation into nude mice [11].…”

Section: Discussionmentioning

confidence: 98%

Direct comparison of current cell-based and cell-free approaches towards the repair of craniofacial bone defects – A preclinical study

et al. 2015

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“…Also, a major concern related to procedures involving MSC is the fate of cells after they enter the host via massive implantation. It remains unknown whether these MSC remain at the grafted site and are specifically responsible for new bone formation, as suggested by some authors [23], [24], or if they die early after implantation and release mediators for cell recruitment from the local environment, as suggested in more recent studies [25]–[27].…”

Section: Introductionmentioning

confidence: 98%

Determining a Clinically Relevant Strategy for Bone Tissue Engineering: An “All-in-One” Study in Nude Mice

et al. 2013

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PurposeAutologous bone grafting (BG) remains the standard reconstruction strategy for large craniofacial defects. Calcium phosphate (CaP) biomaterials, such as biphasic calcium phosphate (BCP), do not yield consistent results when used alone and must then be combined with cells through bone tissue engineering (BTE). In this context, total bone marrow (TBM) and bone marrow-derived mesenchymal stem cells (MSC) are the primary sources of cellular material used with biomaterials. However, several other BTE strategies exist, including the use of growth factors, various scaffolds, and MSC isolated from different tissues. Thus, clinicians might be unsure as to which method offers patients the most benefit. For this reason, the aim of this study was to compare eight clinically relevant BTE methods in an “all-in-one” study.MethodsWe used a transgenic rat strain expressing green fluorescent protein (GFP), from which BG, TBM, and MSC were harvested. Progenitor cells were then mixed with CaP materials and implanted subcutaneously into nude mice. After eight weeks, bone formation was evaluated by histology and scanning electron microscopy, and GFP-expressing cells were tracked with photon fluorescence microscopy.Results/ConclusionsBone formation was observed in only four groups. These included CaP materials mixed with BG or TBM, in which abundant de novo bone was formed, and BCP mixed with committed cells grown in two- and three-dimensions, which yielded limited bone formation. Fluorescence microscopy revealed that only the TBM and BG groups were positive for GFP expressing-cells, suggesting that these donor cells were still present in the host and contributed to the formation of bone. Since the TBM-based procedure does not require bone harvest or cell culture techniques, but provides abundant de novo bone formation, we recommend consideration of this strategy for clinical applications.

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Fate of Bone Marrow Stromal Cells in a Syngenic Model of Bone Formation

Cited by 31 publications

References 48 publications

Mesenchymal stem cells induce endothelial cell quiescence and promote capillary formation

Mesenchymal stem cells induce endothelial cell quiescence and promote capillary formation

Direct comparison of current cell-based and cell-free approaches towards the repair of craniofacial bone defects – A preclinical study

Determining a Clinically Relevant Strategy for Bone Tissue Engineering: An “All-in-One” Study in Nude Mice

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