Vascularization converts the lineage fate of bone mesenchymal stem cells to endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK signaling

Li, Donglin; Cheng, Pengzhen; Jiang, Huijie; Cao, Tianqing; Wang, Jimeng; Gao, Yi; Lin, Yangjing; Wang, Chunmei; Zhang, Shuaishuai; Li, Junqin; Liu, Bin; Song, Yong; Yang, Liu; Pei, Guoxian

doi:10.1038/s41419-018-0999-6

Cited by 15 publications

(12 citation statements)

References 49 publications

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“…18 The higher levels of cell retention and engraftment (human CD90-positive cells were observed inside the scaffolds seeded with human BM-MSCs explanted after 2 months) probably also justify in part the greater observed number of blood vessels, as already described by Shafiee et al 19 Under our experimental conditions, we observed the differentiation of implanted BM-MSCs into ECs (vWF + cells were detected in scaffolds seeded with BM-MSCs alone), as reported for some in vivo studies. 20,21 Our results confirm that transplanted BM-MSCs survived after transplantation and subsequently induced the formation of a vascular network via a paracrine effect and via direct integration into neovessels after differentiation into ECs. Since the transplantation of BM-MSCs alone promotes neovascularization, it might not be worth adding the ECs; this would simplify the treatment process.…”

Section: Discussionsupporting

confidence: 73%

An Alginate-Based Hydrogel with a High Angiogenic Capacity and a High Osteogenic Potential

Barre

Naudot

Colin

et al. 2020

BioResearch Open Access

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In bone tissue engineering, autologous cells are combined with osteoconductive scaffolds and implanted into bone defects. The major challenge is the lack of post-implantation vascular growth into biomaterial. The objective of the present study was to develop a new alginate-based hydrogel that enhances the regeneration of bone defects after surgery. The viability of human bone marrow-derived mesenchymal stem cells (BM-MSCs) or human endothelial cells (ECs) cultured alone or together on the hydrogel was analyzed for 24 and 96 h. After seeding, the cells self-assembled and aggregated to form clusters. For functional validation, empty or cellularized hydrogel matrices were implanted ectopically at subcutaneous sites in nude mice. After 2 months, the matrices were explanted. Transplanted human cells were present, and we observed vessels expressing human von Willebrand factor (resulting from the incorporation of transplanted ECs into neovessels and/or the differentiation of BM-MSCs into ECs). The addition of BM-MSCs improved host vascularization and neovessel formation from human cells, relative to ECs alone. Although we did not observe bone formation, the transplanted BM-MSCs were able to differentiate into osteoblasts. This new biomaterial provided an appropriate three-dimensional environment for transplanted cells and has a high angiogenic capacity and an osteogenic potential.

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Section: Discussionsupporting

confidence: 73%

An Alginate-Based Hydrogel with a High Angiogenic Capacity and a High Osteogenic Potential

Barre

Naudot

Colin

et al. 2020

BioResearch Open Access

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“…Activation of the RhoA/ROCK signaling pathway reduces NO availability, upregulates the expression of the leukocyte adhesion factor ICAM-1 and participates in various inflammatory responses (30,32-34). In addition, RhoA/ROCK signaling causes EC shedding, increases serum levels of vWF and increases the permeability of the vascular endothelium (35). RhoA activation has been demonstrated to be involved in oxidative stress (30).…”

Section: Discussionmentioning

confidence: 99%

Neuregulin‑1 protects cardiac function in septic rats through multiple targets based on endothelial cells

et al. 2019

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The primary mechanism underlying sepsis-induced cardiac dysfunction is loss of endothelial barrier function. Neuregulin-1 (NRG-1) exerts its functions on multiple targets. The present study aimed to identify the protective effects of NRG-1 in myocardial cells, including endothelial, anti-inflammatory and anti-apoptotic effects. Subsequent to lipopolysaccharide (LPS)-induced sepsis, rats were administered with either a vehicle or recombinant human NRG-1 (rhNRG-1; 10 µ g/kg/day) for one or two days. H9c2 cardio-myoblasts were subjected to LPS (10 µ g/ml) treatment for 12 and 24 h with or without rhNRG-1 (1 µ g/ml). Survival rates were recorded at 48 h following sepsis induction. The hemo-dynamic method was performed to evaluate cardiac function, and myocardial morphology was observed. Von Willebrand Factor levels were detected using an immunofluorescence assay. Serum levels of tumor necrosis factor α, interleukin-6, intercellular cell adhesion molecule-1 and vascular endothelial growth factor were detected using an enzyme-linked immuno-sorbent assay; the reductase method was performed to detect serum nitric oxide levels. Apoptosis rates were determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Ras homolog family member A (RhoA) and Rho-associated protein kinase 1 (ROCK1) protein levels were assessed using western blotting. Transmission electron microscopy was used to observe endothelial cells and myocardial ultrastructure changes. Results revealed that NRG-1-treated rats displayed less myocardial damage compared with sham rats. NRG-1 administration strengthened the barrier function of the vasculature, reduced the secretion of endothelial-associated biomarkers and exerted anti-inflammatory and anti-apoptotic effects. In addition, NRG-1 inhibited RhoA and ROCK1 signaling. The results revealed that NRG-1 improves cardiac function, increases the survival rate of septic rats and exerts protective effects via multiple targets throughout the body. The present results contribute to the development of a novel approach to reverse damage to myocardial and endothelial cells during sepsis.

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“…Several mechanisms have been claimed by which MSC exert their therapeutic immunomodulatory effects. This includes, but is not restricted to, cell-to-cell contact or the release of various mediators, including immunosuppressive molecules, growth factors, exosomes, secretomes, chemokines, complement components and various other metabolites [67]. Bioactive cargo in extracellular vesicles (EV) including proteins, microRNA, and mRNA species can impact signaling responses in target cells to modify inflammatory and repair responses.…”

Section: Msc-dependent Immunomodulation and Interaction With The Vmentioning

confidence: 99%

Substantial Overview on Mesenchymal Stem Cell Biological and Physical Properties as an Opportunity in Translational Medicine

Abdelrazik

Giordano

Bròdano

et al. 2019

IJMS

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Mesenchymal stem cells (MSC) have piqued worldwide interest for their extensive potential to treat a large array of clinical indications, their unique and controversial immunogenic and immune modulatory properties allowing ample discussions and debates for their possible applications. Emerging data demonstrating that the interaction of biomaterials and physical cues with MSC can guide their differentiation into specific cell lineages also provide new interesting insights for further MSC manipulation in different clinical applications. Moreover, recent discoveries of some regulatory molecules and signaling pathways in MSC niche that may regulate cell fate to distinct lineage herald breakthroughs in regenerative medicine. Although the advancement and success in the MSC field had led to an enormous increase in the amount of ongoing clinical trials, we still lack defined clinical therapeutic protocols. This review will explore the exciting opportunities offered by human and animal MSC, describing relevant biological properties of these cells in the light of the novel emerging evidence mentioned above while addressing the limitations and challenges MSC are still facing.

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Vascularization converts the lineage fate of bone mesenchymal stem cells to endothelial cells in tissue-engineered bone grafts by modulating FGF2-RhoA/ROCK signaling

Cited by 15 publications

References 49 publications

An Alginate-Based Hydrogel with a High Angiogenic Capacity and a High Osteogenic Potential

An Alginate-Based Hydrogel with a High Angiogenic Capacity and a High Osteogenic Potential

Neuregulin‑1 protects cardiac function in septic rats through multiple targets based on endothelial cells

Substantial Overview on Mesenchymal Stem Cell Biological and Physical Properties as an Opportunity in Translational Medicine

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