Application of mesenchymal stem cells to enhance non‐union bone fracture healing

Abstract

ECM components include a number of osteoinductive and osteoconductive factors, which are involved in bone fracture healing. In this study, a combination of adipose derived mesenchymal stem cells (Ad-MSCs), cancellous bone graft (CBG), and chitosan hydrogel (CHI) was applied to the non-union bone fracture and healing effects were evaluated for the first time. After creation of animal models with non-union fracture in rats, they were randomly classified into seven groups. Radiography at 0, 2, 4, and 8 weeks after surgery, indicated the positive effects of Ad-MSCs + CBG + CHI and Ad-MSCs + CBG in treatment of bone fractures as early as 2 weeks after the surgery. These data were confirmed with both biomechanical and histological studies. Gene expression analyses of Vegf and Bmp2 showed a positive effect of Ad-MSCs on vascularization and osteogenic differentiation in all groups receiving Ad-MSCs, as shown by real-time PCR. Immunofluorescence analysis and RT-PCR results indicated existence of human Ad-MSCs in the fractured region 8 weeks post-surgery. In conclusion, we suggest that application of Ad-MSCs, CBG, and CHI, could be a suitable combination for osteoinduction and osteoconduction to improve non-union bone fracture healing. Further investigations are required to determine the exact mechanisms involved in this process before moving to clinical studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2018.

Allogenic Bone Graft Enriched by Periosteal Stem Cell and Growth Factors for Osteogenesis in Critical Size Bone Defect in Rabbit Model: Histopathological and Radiological Evaluation

“…Thus, we hypothesize that a decellularized allogeneic bone tissue-engineered graft enriched with periosteum derived stem cell and growth factors would provide sustained delivery of growth factors, support stem cell delivery, and improve allograft incorporation in a critical-sized rabbit radius defect. The positive effects of MSCs in the treatment of bone fractures have been demonstrated in several studies (39). Similarly, our results demonstrated that MSCs and cortical bone graft with or without platelet growth factors were effective in accelerating non-union bone fracture healing in rabbits.…”

Adipose-Derived Mesenchymal Stem Cells: A Promising Tool in the Treatment of Musculoskeletal Diseases

“…Around 5 billion dollars are annually spend in treating bone defects in the US, mainly on bone grafts and implants for bone injuries and other pathologies associated with defective fracture healing, such as non-union [98]. Conventional treatments, including autologous bone grafts, and distraction osteogenesis (DO) have some limitations, such as long immobilization periods, donor site morbidity, muscular atrophy and surgical complications such as infection, pain, or hemorrhage [17,99,100]. Tissue engineering and cell-based therapies have been adopted as alternatives therapies to promote bone repair, and AMSCs have been proposed to treat CSDs [100,101,102,103,104,105,106] and delayed fracture healing and the resulting segmental bone defects [99,107,108,109,110].…”

“…Despite advances in fractures treatments, annually, over 5–10% of bone fractures are not able to union [99]. In a study carried out by Ghasroldasht et al, a combination of AMSCs, cancellous bone graft and chitostan hydrogel was applied to non-union bone fractures in rats [99].…”

“…Despite advances in fractures treatments, annually, over 5–10% of bone fractures are not able to union [99]. In a study carried out by Ghasroldasht et al, a combination of AMSCs, cancellous bone graft and chitostan hydrogel was applied to non-union bone fractures in rats [99]. As early as 2 weeks after surgery, radiological assessment revealed that callus formation started at the fracture site and higher healing grade was observed in the AMSCs group.…”

Stammzellen in der Regenerativen Medizin – Translationale Hürden und Möglichkeiten zur Überwindung

“…Als neuer und vielversprechender Ansatz gilt das mechanische Anfrischen der Pseudarthrose und die anschließende Behandlung mit MSCs. Diese werden mit Trägersubstanzen wie Chitosan-oder Hydroxyapatit-fragmenten vermengt und in die Frakturregion eingebracht [81,82].…”