Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results (original) (raw)
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A new preclinical femoral head osteonecrosis model in sheep
2011
Introduction Animal models have been used as insight into the pathogenesis of osteonecrosis, even though most have failed to reproduce all stages of human disease, limiting progression in experimental treatment modalities. A new surgically induced animal model of femoral head osteonecrosis in sheep is presented. Method Osteonecrosis was achieved using an improved method of intracephalic cryogenic lesion by means of a cryoprobe and vascular ligation. Results Histologic Wndings at 6 and 12 weeks showed progression to advanced stage osteonecrosis. MRI, the gold standard in diagnosis and follow-up in human osteonecrosis showed concordant results with histology. Conclusion Our model can therefore be used as a preclinical femoral head osteonecrosis model in an easily accessible animal to assess biological treatments with MRI.
Theoretical biology & medical modelling, 2005
EXPERIMENTAL OSTEONECROSIS: The authors' experience with experimentally produced femoral capital osteonecrosis in rats is reviewed: incising the periosteum at the base of the neck of the femur and cutting the ligamentum teres leads to coagulation necrosis of the epiphysis. The necrotic debris is substituted by fibrous tissue concomitantly with resorption of the dead soft and hard tissues by macrophages and osteoclasts, respectively. Progressively, the formerly necrotic epiphysis is repopulated by hematopoietic-fatty tissue, and replaced by architecturally abnormal and biomechanically weak bone. The femoral heads lose their smooth-surfaced hemispherical shape in the wake of the load transfer through the hip joint such that, together with regressive changes of the joint cartilage and inflammatory-hyperplastic changes of the articular membrane, an osteoarthritis-like disorder ensues. THERAPEUTIC CHOICES: Diverse therapeutic options are studied to satisfy the different opinions conc...
International orthopaedics, 2014
In order to evaluate new therapeutic approaches to human osteonecrosis of the femoral head (ONFH), this study proposed to improve the existing animal model by developing a new surgically induced pig model. First, ONFH was induced with an easy and minimally invasive technique: cryogenic insult with repeated freeze-thaw cycle. Then, to compare and improve the efficacy of this first method, we combined the cryogenic insult to vascular coagulation of the posterior circumflex vessels. Cryoinjury with repeated freeze-thaw cycle alone is sufficient to induce, three weeks postsurgery, a subchondral necrosis as confirmed by magnetic resonance imaging (MRI) and histological analysis. However, a bone regeneration began at four weeks and was complete at eight weeks. To optimise this result, we combined cryoinjury with posterior circumflex vessel coagulation and observed the persistence of ONFH, with progression to collapse at 14 weeks postinduction. Cryoinjury associated with partial vascular c...
Treatment of femoral head osteonecrosis with advanced cell therapy in sheep
Archives of Orthopaedic and Trauma Surgery, 2012
Background The purpose of this study was to evaluate the efficacy of core decompression associated with advanced cell therapy for the treatment of femoral head osteonecrosis in an established sheep model. Methods Early stage osteonecrosis of the right hip was induced cryogenically in 15 mature sheep. At 6 weeks, the sheep were divided into three groups, Group A: core decompression only; Group B: core decompression followed by implantation of an acellular bone matrix scaffold; Group C: core decompression followed by implantation of a cultured BMSC loaded bone matrix scaffold. At 12 weeks, MRI hip studies were performed and then the proximal femur was harvested for histological analysis. Results In the group of advanced cell therapy, Group C, there was a tendency to higher values of the relative surface of newly formed bone with a mean of 20.3 versus 11.27 % in Group A and 13.04 % in Group B but it was not statistically significant. However, the mean relative volume of immature osteoid was 8.6 % in Group A, 14.97 in Group B, and 53.49 % in Group C (p \ 0.05), revealing a greater capacity of osteoid production in the sheep treated with BMSCs. MRI findings were not conclusive due to constant bone edema artifact in all cases. Conclusions Our findings indicate that a BMCSs loaded bone matrix scaffold is capable of stimulating bone regeneration more effectively than isolated core decompression or in association with an acellular scaffold in a preclinical femoral head osteonecrosis model in sheep.
Fuel and Energy Abstracts, 1999
The reparative processes following vascular deprivationinduced necrosis of the femoral head were studied histologically in rats sacrificed 2, 7, 14,21,42 and 92 days postoperatively. The blood supply was severed by incision of the periosteum at the neck of the femoral head and transection of the ligamentum teres. Granulation tissue and a well-vascularized fibrous tissue originating from the joint capsule invaded the necrotic marrow spaces. With progressive resorption of the necrotic tissues and osteoneogenesis, both appositional and intramembranous, within the fibrotic intertrabecular spaces, the r emodeling process led to a shift of the normal spongy architecture of the femoral head to a compacta-like onc. In a few cases, osseous bridges bisected a necrotic physeal cartilage at the latest time intervals. The remodeling was associated with flattening of the femoral heads as well as with degenerative, regenerative and reparative alterations of the articular cartilage. In onc of the two femoral heads obtained three months postoperatively, cystic spaces developed in the fibrous subchondral zone. Our findings are consistent with the view that ineffective attempts at restoring the prenecrotic state of the femoral head by replacing the necrotic with viable tissue triggers the collapse of the femoral head. Thickening and condensation of the subchondral bone, leading to increased stiffness of the subchondral zone, result in the osteoarthritis-like disorder. Mimicking the well-known phases of human osteonecrosis, the model readily allows for preclinical studies of therapeutic regimens.
International orthopaedics, 2018
Osteonecrosis of the femoral head (ONFH) is a significant cause of both pain and disability that often affects young adults during what ought to be their most productive age. Two broad categories of ONFH exist: traumatic and non-traumatic. Traumatic ONFH results from acute mechanical disruption of the femoral head's blood supply. Many factors that increase the risk of non-traumatic osteonecrosis have been identified. Steroid-induced osteonecrosis of the femoral head (SONFH) is the most common form of non-traumatic ONFH. Many hypotheses as to the pathogenesis of SONFH have been proposed, including intravascular thrombosis, abnormal fat metabolism, intramedullary adipocyte hypertrophy, and osteoporosis; however, the exact mechanism of SONFH is still not clearly understood. Animal models using rats, mice, rabbits, chickens, pigs, and emus have been used to study SONFH. Unfortunately, these models each have limitations. Therefore, it is necessary to establish a reproducible model th...
International Journal of Experimental Pathology, 2002
The blood supply of rats 0 femoral heads was severed by cutting the ligamentum teres and stripping the periostium. Histologically, necrosis of the marrow was apparent on the 2nd postoperative day, necrosis of the bone on the 5th postoperative day and fibrous ingrowth on the 7th postoperative day. During the following 5 weeks, progressive resorption of the intertrabecular necrotic debris and necrotic bony trabeculae and subchondral bone plate and, concurrently, appositional and intramembranous new bone formation resulted in remodeling of the femoral heads. In 2 of 7 femoral heads, replacement of the necrotic bone by viable bone was complete at the 42-day postoperative interval. Also, the articular cartilage of the deformed and flattened femoral heads was undergoing degenerative changes. Reduplicating the pathogenically inferred clinical settings of blood supply deprivation, it is proposed that this model, in a small laboratory animal, satisfies the requirements sought for preclinical studies of treatment modalities of avascular osteonecrosis in man.
Osteoarthritis and Cartilage, 2018
OBJECTIVE: The experimental induction of cam-type femoroacetabular impingement (FAI) in sheep is established. To tap the full potential of this ovine model, one should be able to perform a femoral osteochondroplasty safely. This study was based on previous cadaver experiments on the blood supply to the ovine femoral head and on the biomechanical strength of the proximal femur following offset creation. We hypothesized that offset creation in this ovine FAI model does not lead to (1) avascular necrosis (AVN) of the ovine femoral head or (2) iatrogenic femoral neck fractures and (3) can be performed effectively. DESIGN: In this experimental, controlled, prospective study nine sheep underwent unilateral FAI induction through an intertrochanteric, varus osteotomy. Seventy days following FAI induction, femoral osteochondroplasty was performed. Sheep were sacrificed after another 140 days. Radiographs, computed tomography (CT) scans and MRI were acquired. Histologic samples were stained with hematoxylin-eosin. (1) The multimodal Association Research Circulation Osseous (ARCO) classification was used for assessment of AVN. (2) Femoral neck fractures were assessed with the multimodal imaging approach. (3) Pre-and postoperative (=after sacrifice) alpha angles and femoral neck diameters were compared. RESULTS: (1) No signs for AVN according to the ARCO classification or (2) for femoral neck fractures were detected. (3) Mean alpha angles and femoral neck diameters decreased superiorly by at least 30°respectively 4 mm after the offset creation. CONCLUSIONS: Femoral osteochondroplasty can be performed effectively and without the risk of AVN or femoral neck fractures in ovine FAI.