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

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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Increased Internal Porosity and Surface Area of Hydroxyapatite Accelerates Healing and Compensates for Low Bone Marrow Mesenchymal Stem Cell Concentrations in Critically-Sized Bone Defects

Applied Sciences ◽

10.3390/app8081366 ◽

2018 ◽

Vol 8 (8) ◽

pp. 1366 ◽

Cited By ~ 5

Author(s):

Eileen Dawson ◽

Richard Suzuki ◽

Melissa Samano ◽

Matthew Murphy

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Bone Regeneration ◽

Autologous Bone Marrow ◽

Bone Defects ◽

Porous Hydroxyapatite ◽

Handling Characteristics ◽

Skeletal Defects

For clinical treatment of skeletal defects, osteoinductive scaffolds must have the ability to conform to the unique geometry of the injury site without sacrificing biologically favorable properties, including porosity. This investigation seeks to combine the osteoinductive properties of porous hydroxyapatite (HA) scaffolds with the beneficial handling characteristics of granules or putties, while evaluating the effects of mesenchymal stem cell (MSC) concentration on the composite grafts’ ability to regenerate bone in vivo. The results demonstrate that porous HA granules regenerate significantly larger volumes of bone compared to non-porous HA. Increased MSC concentrations in autologous bone marrow aspirate (BMA) contributed to greater bone regeneration. This effect was most predominant with non-porous HA. While the extent of bone regeneration using non-porous HA was strongly correlated with MSC concentration of the marrow, porous HA microparticles combined with autologous BMA were successful in faster treatment of critically-sized bone defects and with less dependence on the MSC concentration than non-porous HA.

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

The International Journal of Artificial Organs ◽

10.1177/03913988211025538 ◽

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.

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