Bone regeneration potential of allogeneic or autogeneic mesenchymal stem cells loaded onto cancellous bone granules in a rabbit radial defect model

Abstract

For developing a clinically effective bone regeneration strategy, we compare the bone regeneration potential of cultured allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) and of autologous BM-MSCs loaded onto allogeneic cancellous bone granule scaffolds. A critical-sized segmental bone defect was made at the mid-shaft of both radiuses in 19 New Zealand White rabbits (NWRs). In the experimental group, allogeneic BM-MSCs loaded onto small-sized allogeneic cancellous bone granules (300~700 um in diameter) were implanted in one side of a bone defect. In the control group, autologous BM-MSCs loaded onto allogeneic cancellous granules were grafted in the other side. Bone regeneration was assessed by radiographic evaluation at 4, 8, 12 and 16 weeks post-implantation and by micro-computed tomography (micro-CT) and histological evaluation at 8 and 16 weeks. The experimental groups showed lower bone quantity indices (BQIs) than the control groups at 12 and 16 weeks (p < 0.05), although no significant difference was observed at 4 and 8 weeks (p > 0.05). Micro-CT analysis revealed that both groups had similar mean total bone volume and other parameters including trabecular thickness, number and separation at either 8 or 16 weeks. Only bone surface area revealed less area in the experimental group at 16 weeks. Histological evaluation of 8-week and 16-week specimens showed similar biologic processes of new bone formation and maturation. There was no inflammatory reaction indicating an adverse immune response in both allogeneic and autologous MSC groups. In conclusion, allogeneic BM-MSCs loaded onto allogeneic cancellous bone granules had comparable bone regeneration potential to autologous BM-MSCs in a rabbit radial defect model.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Considering the wide diversity of conducted research, investigators should be extremely cautious to translate conclusion in-between models and species and pay special attention in designing the animal studies to draw valuable and reproducible results. Mouse: [185], [186] Rat: [187] (DM), [188] Rabbit: [189], [190], [191], [192] Dog: [193], [194] Sheep/Goat: [167], [170], [176], [195], [196], [197] human BM-derived MPCs…”

The Effect of Autologous Platelet-Rich Plasma on Bone Regeneration by Autologous Mesenchymal Stem Cells Loaded onto Allogeneic Cancellous Bone Granules

“…The entire process was performed as in previous studies from our lab [Lee et al, 2010[Lee et al, , 2014Kim et al, 2012;Kang et al, 2014]. In brief, rabbits were anesthetized, and 10 mL BM were aspirated by penetrating the cortex of the posterior iliac crest of each animal using an 18-gauge needle attached to a 50-mL syringe containing 0.6 mL heparinized saline solution (3,000 U heparin).…”

“…This process was also performed as in previous studies from our lab [Lee et al, 2010[Lee et al, , 2014Kim et al, 2012;Kang et al, 2014]. Allogeneic cancellous bone was harvested from iliac crests, proximal and distal femurs, and the proximal tibias of NWR weighing 2.5 kg.…”

“…Three independent examiners assessed the plain radiograph images in terms of the volume (V) and density (D) of regenerated bone using our 5 criteria ( Table 1 ), 3 times, respectively, at 3-week intervals. The quantity of regenerated bone (bone quantity index; BQI) was calculated using the following equation: BQI 2 = V × D, where V denotes the assessed mean bone volume and D denotes the assessed mean bone density [Lee et al, 2010[Lee et al, , 2014Kim et al, 2012;Kang et al, 2014].…”

Porous biphasic calcium phosphate ceramics coated with nano-hydroxyapatite and seeded with mesenchymal stem cells for reconstruction of radius segmental defects in rabbits

“…The grafts were covered with the surrounding muscle sutured in place with an absorbable 2-0 polyglactin suture. Finally, the skin was sutured closed with 3-0 silk threads, and 400,000 U of penicillin was administered each day for 3 days to prevent infection [35].…”