Bone Regeneration Using Mesenchymal Stem Cells: Challenges and Future Perspectives in Regenerative Surgery

Sabali, Maja; Mangano, Alessandro; Lianos, Georgios D; Boni, Luigi; Dionigi, Gianlorenzo; Mangano, Alberto

doi:10.2217/rme.15.35

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…The safety issues of genetic modification techniques have always been an intractable challenge in stem cellbased tissue engineering [5,14,[29][30][31]. For example, the viral vector used in gene therapy has genotoxicity issues [32], and the off-target mutations or effects of techniques like CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats, associated RNA guided endonuclease Cas9, [33,34]) or RNA interference [35] might exert detrimental toxic effects and induce unwanted phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria transfer enhances proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell and promotes bone defect healing

et al. 2020

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Background: Bone marrow-derived mesenchymal stem cell (BMSC) transplantation is considered a promising therapeutic approach for bone defect repair. However, during the transplantation procedure, the functions and viability of BMSCs may be impaired due to extended durations of in vitro culture, aging, and disease conditions of patients. Inspired by spontaneous intercellular mitochondria transfer that naturally occurs within injured tissues to rescue cellular or tissue function, we investigated whether artificial mitochondria transfer into pre-transplant BMSCs in vitro could improve cellular function and enhance their therapeutic effects on bone defect repair in situ.

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Section: Discussionmentioning

confidence: 99%

Mitochondria transfer enhances proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell and promotes bone defect healing

et al. 2020

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“…242 Also, several questions need to be answered before these procedures can be clinically translated. 243 First, it is important to determine the molecular immune mechanisms and cells that are involved in these responses, the dynamic fate of these implanted ASCs, assessment of its clinical efficiency and factors that influence these inconsistent results. 244 …”

Section: Challengesmentioning

confidence: 99%

Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering

2016

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Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors (GFs), it makes stem cells the ideal agents for bone regeneration. Furthermore, platelet-rich plasma (PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future.

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“…The safety issues of genetic modification techniques have always been an intractable challenge in stem-cell based tissue engineering [5,14,[29][30][31]. For example, viral vector used in gene therapy has genotoxicity issues [32], and the off-target mutations or effects of techniques like CRISPR-Cas9…”

Section: Discussionmentioning

confidence: 99%

Mitochondria transfer enhances bone marrow mesenchymal stem cell functions and promotes bone defect healing

Guo¹,

Chi²,

Wang³

et al. 2020

Preprint

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Background: Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation is considered a promising therapeutic approach for bone defect repair. However, during the transplantation procedure, the functions and viability of BMSCs may be impaired due to extended durations of in vitro culture, aging and disease conditions of patients. Inspired by spontaneous intercellular mitochondria transfer that naturally occurs within injured tissues to rescue cellular or tissue function, we investigated whether artificial mitochondria transfer into pre-transplant BMSCs in vitro could improve cellular function and enhance their therapeutic effects on bone defect repair in situ. Methods: First, mitochondria were isolated from donor BMSCs and transferred into recipient BMSCs of the same passage. Afterwards, changes in proliferative capability was evaluated by Cell Counting Kit-8, Ki67 staining, etc., while Transwell, wound scratch healing and cell motility tests were conducted to determine migration ability. Then, alkaline phosphatase (ALP) staining, Alizarin Red staining, combined with qPCR and Western Blot experiments of Runx2 and BMP2 were performed to elucidate the effect of mitochondria transfer on the osteogenic potential of BMSCs in vitro. After that, the in vivo experiments were completed by transplanting mitochondria-recipient BMSCs into a rat cranial critical-size bone defect model. Micro CT scanning and histological analysis were conducted 4 weeks and 8 weeks after transplantation to evaluate the osteogenesis effect in situ. Finally, in order to discover the potential connection between cellular behavioral changes and aerobic metabolism, OXPHOS (oxidative phosphorylation) and ATP production were assessed and inhibition of aerobic respiration by oligomycin was proceeded. Results: Mitochondria-recipient BMSCs exhibited significantly enhanced proliferation and migration, and increased osteogenic differentiation upon osteogenic induction. The in vivo results showed more new bone formation after transplantation of mitochondria-recipient BMSCs in situ. Increased OXPHOS activity and ATP production were further observed, whereas the inhibition of which impaired the enhancement of proliferation, migration and osteogenic differentiation induced by mitochondria transfer. Conclusions: Mitochondria transfer is a feasible technique to enhance BMSCs function in vitro and promote bone defect repair in situ through the up-regulation of aerobic metabolism. The results indicated that mitochondria transfer may be a novel promising technique for optimizing stem cell function.

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Bone Regeneration Using Mesenchymal Stem Cells: Challenges and Future Perspectives in Regenerative Surgery

Cited by 4 publications

References 25 publications

Mitochondria transfer enhances proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell and promotes bone defect healing

Mitochondria transfer enhances proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cell and promotes bone defect healing

Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering

Mitochondria transfer enhances bone marrow mesenchymal stem cell functions and promotes bone defect healing

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