Background: The aim was to observe the distribution of autologous bone marrow mesenchymal stem cells with intra-arterial infusion in osteonecrosis of the femoral head (ONFH) in dogs.
Methods: Twelve mature male Beagle dogs were randomly divided into two groups: MSCs group and control group. ONFH models were established by a liquid nitrogen freezing method. MSCs were isolated, cultured, identified, and labelled. Three weeks after establishment of ONFH models, intra-arterial infusion was performed. 6 dogs in MSCs group were injected with 1 ml MSCs (5X1061X107/ml), while 0.9% normal saline was used in control group. The dogs were sacrificed at eight weeks after intra-arterial infusion. Changes in general architecture of the femoral heads were determined by hematoxylin and eosin stain. The differentiation of grafted cells in the femoral heads was observed by immunofluorescence, and distributions of grafted cells in vital organs were observed through immunohistochemistry (IHC) and histomorphometry.
Results: Trabecular bone volume was increased and empty lacunae rate was decreased in MSCs group (p<0.05). Most of the BrdU-positive MSCs in necrotic region of MSC-transplanted femoral heads co-stained together with osteocalcin. Simultaneously, the BrdU-positive MSCs were nonuniformly distributed in vital organs and the number of BrdU-positive cells in kidney (IOD/Area=0.050±0.0013), gallbladder (IOD/Area=0.032±0.0020) and liver (IOD/Area=0.023±0.0026) were obviously higher than those in small bowel (IOD/Area=0.005±0.0009), prostate (IOD/Area=0.005±0.0006), testicle (IOD/Area=0.003±0.0004) and spleen (IOD/Area=0.003±0.0002). Furthermore, no immunological rejection and graft versus host disease appeared in dogs after transplantation.
Conclusions: MSCs with intra-arterial infusion can migrate into the necrotic field of femoral head and directionally differentiate into osteoblasts, and then improve repair of femoral head. Furthermore, MSCs were unequally distributed in vital organs but no conflict with physical condition could appear. Autologous bone marrow MSCs with intra-arterial infusion may be a feasible and safe avenue for the treatment of femoral head necrosis.
Disclosure: he authors declared no competing interests. This work was supported by the National Natural Science Foundation of China (Grants No.81202710 and 81273770) and the Science Technology Department of Zhejiang Province (Grants No.2011R50022-01 and 2012C37087).