In vivo study of the angiogenesis potential of bone marrow-derived mesenchymal stem cell aggregates in their niche like environment

2021 ◽  
pp. 039139882110255
Author(s):  
Sara Anajafi ◽  
Azam Ranjbar ◽  
Monireh Torabi-Rahvar ◽  
Naser Ahmadbeigi
Keyword(s):  
Tissue Engineering ◽  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cultured Cells ◽  
Morphological Evidence ◽  
Cell Aggregates ◽  
Plla Scaffold ◽  
Significant Difference

Background: Sufficient blood vessel formation in bioengineered tissues is essential in order to keep the viability of the organs. Impaired development of blood vasculatures results in failure of the implanted tissue. The cellular source which is seeded in the scaffold is one of the crucial factors involved in tissue engineering methods. Materials and methods: Considering the notable competence of Bone Marrow derived Mesenchymal Stem Cell aggregates for tissue engineering purposes, in this study BM-aggregates and expanded BM-MSCs were applied without any inductive agent or co-cultured cells, in order to investigate their own angiogenesis potency in vivo. BM-aggregates and BM-MSC were seeded in Poly-L Lactic acid (PLLA) scaffold and implanted in the peritoneal cavity of mice. Result: Immunohistochemistry results indicated that there was a significant difference ( p < 0.050) in CD31+ cells between PLLA scaffolds contained cultured BM-MSC; PLLA scaffolds contained BM-aggregates and empty PLLA. According to morphological evidence, obvious connections with recipient vasculature and acceptable integration with surroundings were established in MSC and aggregate-seeded scaffolds. Conclusion: Our findings revealed cultured BM-MSC and BM-aggregates, capacity in order to develop numerous connections between PLLA scaffold and recipient’s vasculature which is crucial to the survival of tissues, and considerable tendency to develop constructs containing CD31+ endothelial cells which can contribute in vessel’s tube formation.

scholarly journals Radiation-Induced Osteocyte Senescence Alters Bone Marrow Mesenchymal Stem Cell Differentiation Potential via Paracrine Signaling

2021 ◽  
Vol 22 (17) ◽  
pp. 9323
Author(s):  
Linshan Xu ◽  
Yuyang Wang ◽  
Jianping Wang ◽  
Jianglong Zhai ◽  
Li Ren ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cellular Senescence ◽  
Adipogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Paracrine Signaling ◽  
Differentiation Potential ◽  
Radiation Induced

Cellular senescence and its senescence-associated secretory phenotype (SASP) are widely regarded as promising therapeutic targets for aging-related diseases, such as osteoporosis. However, the expression pattern of cellular senescence and multiple SASP secretion remains unclear, thus leaving a large gap in the knowledge for a desirable intervention targeting cellular senescence. Therefore, there is a critical need to understand the molecular mechanism of SASP secretion in the bone microenvironment that can ameliorate aging-related degenerative pathologies including osteoporosis. In this study, osteocyte-like cells (MLO-Y4) were induced to cellular senescence by 2 Gy γ-rays; then, senescence phenotype changes and adverse effects of SASP on bone marrow mesenchymal stem cell (BMSC) differentiation potential were investigated. The results revealed that 2 Gy irradiation could hinder cell viability, shorten cell dendrites, and induce cellular senescence, as evidenced by the higher expression of senescence markers p16 and p21 and the elevated formation of senescence-associated heterochromatin foci (SAHF), which was accompanied by the enhanced secretion of SASP markers such as IL-1α, IL-6, MMP-3, IGFBP-6, resistin, and adiponectin. When 0.8 μM JAK1 inhibitors were added to block SASP secretion, the higher expression of SASP was blunted, but the inhibition in osteogenic and adipogenic differentiation potential of BMSCs co-cultured with irradiated MLO-Y4 cell conditioned medium (CM- 2 Gy) was alleviated. These results suggest that senescent osteocytes can perturb BMSCs’ differential potential via the paracrine signaling of SASP, which was also demonstrated by in vivo experiments. In conclusion, we identified the SASP factor partially responsible for the degenerative differentiation of BMSCs, which allowed us to hypothesize that senescent osteocytes and their SASPs may contribute to radiation-induced bone loss.

Graphene Oxide Enables the Reosteogenesis of Previously Contaminated Titanium In Vitro

2020 ◽  
Vol 99 (8) ◽  
pp. 922-929
Author(s):  
W. Qin ◽  
C. Wang ◽  
C. Jiang ◽  
J. Sun ◽  
C. Yu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Graphene Oxide ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Osteogenic Potential ◽  
Implant Surface ◽  
Significant Difference ◽  
Titanium Surfaces ◽  
Group B

The main goal of peri-implantitis treatment is to control infection and arrest bone loss, which requires the removal of polymicrobial biofilms on the implant surface and the reduction of tissue invasion. Additionally, prognosis can be improved if reosseointegration occurs on previously contaminated implants. To evaluate whether graphene oxide (GO) can remove polymicrobial biofilms, biofilms were established on titanium surfaces in vitro and treated with different methods: group B, removed only with brushing; group G, treated with different GO concentrations (64, 128, 256, and 512 μg/mL); group GB, combined treatments of groups B and G; and group C, untreated. Subsequently, to evaluate reosteogenesis on previously contaminated titanium, 4 groups were used: groups C, B, GB-256, and GB-512 (treated with 256 and 512 μg/mL of GO, respectively). Intact clean titanium (IC) was used as a control. Additionally, cell behavior on IC treated with GB-256 (IGB-256) and GB-512 (IGB-512) was compared with that of the GB-256 and GB-512 groups, respectively. The results showed that at high concentrations (≥256 μg/mL), GO eliminated residual bacteria and inhibited biofilm reformation after brushing, whereas neither GO nor brushing alone could achieve this. Bone marrow–derived mesenchymal stem cell viability in groups GB-256 and IC was higher than that in groups GB-512, C, and B ( P < 0.05). No significant difference was found between group GB-256 and group IC ( P > 0.05). Osteogenic differentiation of bone marrow–derived mesenchymal stem cells in group GB-256 was higher than that in groups IC, GB-512, C, and B. No difference was found between groups IGB-256 and IGB-512 and groups GB-256 and GB-512, respectively ( P > 0.05). In conclusion, 256 μg/mL of GO combined with brushing significantly removed polymicrobial biofilms that remained on the previously contaminated titanium surfaces. The bone marrow–derived mesenchymal stem cell osteogenic potential was regained or even enhanced on the titanium surfaces treated this way in vitro, which might provide a new idea for treating peri-implantitis.

scholarly journals Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Bo Liang ◽  
Jia-Ming Liang ◽  
Jia-Ning Ding ◽  
Jia Xu ◽  
Jian-Guang Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Bone Regeneration ◽  
Rat Model ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Mtor Pathway ◽  
Calvarial Defect

Abstract Background Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved. Methods To investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization. Results DMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo. Conclusions Low doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.

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