IN VIVO OSTEOGENETIC POTENTIAL BONE MARROW MESENCHYMAL STEM CELL ON β-TRICALCIUM PHOSPHATE (β-TCP) / COLLAGEN SPONGE

ASAIO Journal ◽  
2003 ◽  
Vol 49 (2) ◽  
pp. 209
Author(s):  
T Matsuno ◽  
T Nakamura ◽  
K Kuremoto ◽  
T Satoh ◽  
Y Shimizu
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Tricalcium Phosphate ◽  
Collagen Sponge

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.

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.

Immortalized human fetal bone marrow-derived mesenchymal stem cell expressing anti-tumor suicide gene for anti-tumor therapy in vitro and in vivo

Cytotherapy ◽  
2013 ◽  
Vol 15 (4) ◽  
pp. S55
Author(s):  
W.Y. Lee ◽  
T. Zhang ◽  
C.P. Lau ◽  
C.C. Wang ◽  
K.M. Chan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Tumor Therapy ◽  
Suicide Gene ◽  
Fetal Bone

scholarly journals Human bone marrow mesenchymal stem cell-derived exosomes stimulate cutaneous wound healing mediates through TGF-β/Smad signaling pathway

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiechao Jiang ◽  
Zhongyu Wang ◽  
Ji Sun
Keyword(s):  
Bone Marrow ◽  
Wound Healing ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Signaling Pathway ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Skin Cells ◽  
Smad Signaling Pathway

Abstract Background Cutaneous wound healing represents a morphogenetic response to injury and is designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cell-derived exosomes (hBM-MSC-Ex) are a promising source for cell-free therapy and skin regeneration. Methods In this study, we investigated the cell regeneration effects and its underlying mechanism of hBM-MSC-Ex on cutaneous wound healing in rats. In vitro studies, we evaluated the role of hBM-MSC-Ex in the two types of skin cells: human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs) for the proliferation. For in vivo studies, we used a full-thickness skin wound model to evaluate the effects of hBM-MSC-Ex on cutaneous wound healing in vivo. Results The results demonstrated that hBM-MSC-Ex promote both two types of skin cells’ growth effectively and accelerate the cutaneous wound healing. Interestingly, we found that hBM-MSC-Ex significantly downregulated TGF-β1, Smad2, Smad3, and Smad4 expression, while upregulated TGF-β3 and Smad7 expression in the TGF-β/Smad signaling pathway. Conclusions Our findings indicated that hBM-MSC-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-β/Smad signal pathway. The current results provided a new sight for the therapeutic strategy for the treatment of cutaneous wounds.

scholarly journals Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model

2019 ◽  
Vol 20 (21) ◽  
pp. 5468 ◽  
Author(s):  
Sicheng Wen ◽  
Mark Dooner ◽  
Elaine Papa ◽  
Michael Del Tatto ◽  
Mandy Pereira ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Fibroblast Cell ◽  
Irradiation Damage ◽  
Hematopoietic Tissue ◽  
Human Lung Fibroblast ◽  
Post Radiation

We have previously shown that injury induced by irradiation to murine marrow can be partially or completely reversed by exposure to human or murine mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). Investigation of the biodistribution of EVs in vivo is essential for understanding EV biology. In this study, we evaluated the DiD lipid dye labeled MSC-EV biodistribution in mice under different conditions, including different MSC-EV doses and injection schedules, time post MSC-EV injection, and doses of radiation. DiD-labeled MSC-EVs appeared highest in the liver and spleen; lower in bone marrow of the tibia, femur, and spine; and were undetectable in the heart, kidney and lung, while a predominant EV accumulation was detected in the lung of mice infused with human lung fibroblast cell derived EVs. There was significantly increased MSC-EV accumulation in the spleen and bone marrow (tibia and femur) post radiation appearing with an increase of MSC-EV uptake by CD11b+ and F4/80+ cells, but not by B220 cells, compared to those organs from non-irradiated mice. We further demonstrated that increasing levels of irradiation caused a selective increase in vesicle homing to marrow. This accumulation of MSC-EVs at the site of injured bone marrow could be detected as early as 1 h after MSC- EV injection and was not significantly different between 2 and 24 h post MSC-EV injection. Our study indicates that irradiation damage to hematopoietic tissue in the spleen and marrow targets MSC-EVs to these tissues.

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