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A unique feature of Epistemonikos is that it connects systematic reviews and their included studies. This allows clustering systematic reviews based on the primary studies they have in common. The concept of 'systematic reviews sharing included studies' is a proxy of 'systematic reviews answering a similar question'.

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7 Primary studies 28.6%Randomized controlled trial (RCT)2 / 7
Zhao D2012Wang BL2010Hernigou P2009Sen RK2012Gangji V2011Gangji V2005Liu Y2013
2 Systematic reviews
Lau RL2014Li X2014
10 References ( articles) loading Revert Studify

Primary study

Unclassified

The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head.

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Authors Sun Y , Feng Y , Zhang C
Journal Joint, bone, spine : revue du rhumatisme
Year 2009
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OBJECTIVE: We examined whether implantation of autologous bone marrow mononuclear cells (BM-MNC) can augment neovascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. METHODS: Sixty-five 28-week-old male New Zealand white rabbits were divided into group I (left untreated, N=20), group II (core decompression, N=20) and group III (core decompression+autologous bone marrow cells implantation, N=25) after receiving an established inductive protocol for inducing steroid-associated ON. Four weeks later, these rabbits were euthanized, bilateral femora were dissected for micro-CT-based microangiography to assess vascularization, and then the osteonecrotic changes and repair processes were examined histopathologically. RESULTS: Quantitative analysis showed that new vessel formation in group III was significantly greater compared with other groups at 4 weeks after treatment. Penetrating capillary vessels number vessels number in group III (44.5+/-5.11) was significantly larger than that of group II (11.4+/-2.46) and group I (3.10+/-0.33) (p<0.01). The histologic and histomorphometric analysis revealed that the new bone volume was significantly higher in the group III than in the group I and II, 4 weeks after treatment. CONCLUSION: In this animal model, a combination of bone marrow mononuclear cells and core decompression enhance the neovascularization and the osteoinductive ability, resulting in bone regeneration. These findings confirm the preliminary clinical results obtained in humans that the implantation of bone marrow mononuclear cells is an effective and feasible method for treating early osteonecrosis.

Primary study

Unclassified

Treatment of avascular necrosis of the femoral head by hepatocyte growth factor-transgenic bone marrow stromal stem cells.

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Authors Wen Q , Ma L , Chen YP , Yang L , Luo W , Wang XN
Journal Gene therapy
Year 2008
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The treatment of hormone-induced early-stage avascular necrosis of the femoral head (ANFH) with transplantation of hepatocyte growth factor (HGF)-transgenic bone marrow stromal stem cells (BMSCs) was examined. A rabbit model of hormone-induced early ANFH was first established. BMSCs were transplanted by core decompression under the guidance of computed tomography (CT). A supportive fibrinogen drug delivery mixture (FG) was tested for mechanical enhancement of stem cell delivery. Therapeutic efficacy was evaluated by CT, magnetic resonance imaging (MRI), CT perfusion imaging, ink artery infusion angiography, hematoxylin-and-eosin staining and immunohistochemical staining for extracellular signal-regulated kinase-1/2 of pathological sections. A regular arrangement of trabeculae and obvious bone regeneration were observed in the animals receiving transplanted transgenic BMSCs with FG. Newly generated capillaries were visible on the bone plates of the trabeculae, and the bone marrow was rich in hematopoietic tissue. These results demonstrate that the combination of core decompression and transplantation of HGF transgenic autologous BMSCs enhanced blood vessel regeneration and bone reconstruction in the ANFH model. This study provides experimental data that motivate possible clinical use of this therapeutic strategy.

Primary study

Unclassified

Treatment of early avascular necrosis of femoral head by small intestinal submucosal matrix with peripheral blood stem cells.

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Journal Transplantation proceedings
Year 2011
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BACKGROUND: Avascular necrosis of the femoral head (ANFH) is a highly mutilating disease. There are no effective ways to treat early femoral head ischemia. Peripheral blood stem cell (PBSC) transplantation may be superior to conventional bone marrow transplantation. Small intestinal submucosae matrix (SIS) is composed of highly conserved collagens, glycoproteins, proteoglycans, and glycoaminoglycans in their natural configuration and concentrations. When implanted in a number of microenvironments in vivo, SIS has been used to induce proliferation, remodeling, and regeneration of host tissues. This study was designed to verify the curative effects of PBSC and SIS transplantation-induced vascular regeneration to improve ischemic femoral head necrosis in rabbits. METHODS: 32 New Zealand white rabbits underwent ischemic femoral head necrosis modeling in both hindlimbs by liquid-nitrogen refrigeration. All rabbits were intraperitoneally injected with grannlocytectomy-stimulating factor (250 μg/kg/d), except for normal control subjects injected with equivalent saline solution. After separation of peripheral blood stem cells (PBSCs), 64 femoral heads in 32 rabbits were randomly divided into 4 groups: group A, cancellous bone and peripheral blood stem cells cultured with small intestinal submucosa; group B, cancellous bone and PBSCs; group C, cancellous bone autografts; and group D, no treatment. The specimens were harvested at 4 and 8 weeks after surgery. All specimens were examined to observe angiogenesis and osteogenesis repairing the avascular necrosis of the femoral head by using gross observation, x-ray, histology, and immunohistochemical staining. RESULTS: In 4 weeks after peripheral stem cell transplantation, the standing ability and activity of the transplanted hindlimbs were improved remarkably, but there were no obvious changes in the control limbs. X-rays showed a greater density of grafts than the host bone in groups A,B, and group C was unchanged at 4 weeks. Histology revealed many osteoprogenitor cells and osteoblasts and no inflammatory cell infiltration at 4 weeks with much new bone formed at 8 weeks in group A and at 4 weeks in group B. The cancellous bone autograft was absorbed completely at 8 weeks in group C. There was little osteoid tissue formed in group D at 8 weeks. The zone of new bone formation in group A was greater than that in group B (P < .05), but there was no significant difference between groups A and C (P > .05). Immunohistochemical staining with CD31 mouse antibody showed greater amounts and zones of new blood vessels in groups A and B at 4 and 8 weeks and little evidence in group D. There was no significant difference between groups A and B (P > .05) and significant differences between groups A and B versus C and D (P < .05). CONCLUSION: Transplantation of PBSCs cultured with SIS effectively improved ischemic femoral head necrosis.

Primary study

Unclassified

Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head.

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Authors Yan Z , Hang D , Guo C , Chen Z
Journal Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Year 2009
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The purpose of this study was to investigate the survival and differentiation status of MSCs transplanted to ONFH. Traumatic ONFH was surgically produced in skeletally mature mongrel dogs. Osteonecrosis was treated with either saline (control) or autologous mesenchymal stem cells (MSCs) transplantation after decompression. Green fluorescent protein (GFP) was used to track the transplanted MSCs, the differentiation of MSCs were evaluated by fluorescent double-labeling with GFP between osteocalcin or von Willebrand factor (vWF) at 2nd, 8th, and 12th week after the transplantation. It was demonstrated that GFP-positive cells were present in the necrotic area up to 12 weeks after the transplantation, their number increased from 15% at 2nd week to 38% at 12th week (p < 0.05). Neither osteocalcin nor vWF was detected by immunocytochemistry in GFP-labeled MSCs in vitro, but osteocalcin was immunohistochemically positive in 90% of the GFP-labeled MSCs in vivo, while vWF was still negative. The vWF expression was of no significant difference between the control group and MSCs-transplanted group. The percentages of trabeculae bone volume were 9.36% and 8.42% at 2nd week (p > 0.05), 22.82% and 14.72% at 8th week, and 31.08% and 20.66% at 12th week (p < 0.05) in MSCs-transplanted group and control group, respectively; new trabeculae bone in MSCs-transplanted group was significantly increased as compared to that of control group at 8th and 12th week. The results demonstrated that the transplanted MSCs could survive, proliferate, and differentiate into osteoblasts directly, which contributed to the accelerated repair process. The possible mechanism is site-dependant differentiation.

Primary study

Unclassified

Successful transplant of mesenchymal stem cells in induced osteonecrosis of the ovine femoral head: preliminary results.

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Journal Acta cirúrgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia
Year 2010
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PURPOSE: Evaluate the bone tissue recovery following transplantation of ovine mesenchymal stem cells (MSC) from bone marrow and human immature dental-pulp stem cells (hIDPSC) in ovine model of induced osteonecrosis of femoral head (ONFH). METHODS: Eight sheep were divided in three experimental groups. First group was composed by four animals with ONFH induced by ethanol through central decompression (CD), for control group without any treatment. The second and third group were compose by two animals, six weeks after ONFH induction received transplantation of heterologous ovine MSC (CD + oMSC), and hIDPSC (CD + hIDPSC), respectively. In both experiments the cells were transplanted without application of any type of immunosupression protocol. RESULTS: Our data indicate that both cell types used in experiments were able to proliferate within injured site providing bone tissue recovery. The histological results obtained from CD+hIDPSC suggested that the bone regeneration in such animals was better than that observed in CD animals. CONCLUSION: Mesenchymal stem cell transplant in induced ovine osteonecrosis of femoral head by central decompression technique is safe, and apparently favors bone regeneration of damaged tissues.

Primary study

Unclassified

Beneficial effect of autologous transplantation of endothelial progenitor cells on steroid-induced femoral head osteonecrosis in rabbits.

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Authors Sun Y , Feng Y , Zhang C , Cheng X , Chen S , Ai Z , Zeng B
Journal Cell transplantation
Year 2011
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Femoral head osteonecrosis (ON) is a serious complication of steroid administration. We examined whether implantation of autologous bone marrow-derived endothelial progenitor cells (EPCs) can augment neovascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. Forty 12-week-old male New-Zealand white rabbits were divided into group I (left untreated, n=12), group II (core decompression, n=12), and group III (core decompression + autologous EPCs implantation, n=16) after receiving an established inductive protocol for inducing steroid-associated ON. Four weeks later, these rabbits were euthanized, bilateral femora were dissected for Micro-CT-based microangiography to assess vascularization, and then the osteonecrotic changes and repair processes were examined histopathologically. Quantitative analysis showed that new vessel formation in group III was significantly greater compared with other groups at 4 weeks after treatment. The histologic and histomorphometric analyses revealed that the new bone volume was significantly higher in group III than in groups I and II 4 weeks after treatment. A combination of EPCs and core decompression enhances the neovascularization and bone regeneration in rabbit steroid-induced femoral head ON. Local implantation of EPCs may provide a novel and effective therapeutic option for early corticosteroid-induced ON.

Primary study

Unclassified

Therapeutic effect of osteogenically induced adipose derived stem cells on vascular deprivation-induced osteonecrosis of the femoral head in rabbits.

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Journal Chinese journal of traumatology = Zhonghua chuang shang za zhi / Chinese Medical Association
Year 2011
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OBJECTIVE: To explore the therapeutic effect of osteogenically induced adipose-derived stem cells (ADSCs) on vascular deprivation-induced osteonecrosis of the femoral head (ONFH) in rabbit model. METHODS: Vascular deprivation-induced ONFH was established by intramuscular injection of methylpre- dnisolone, and vascular occlusion of the capital femoral epiphysis by electrocoagulation in adult New Zealand white rabbits. Eight weeks after the establishment of vascular deprivation-induced ONFH, animals were randomly divided into three equal groups. In Group A (control), no therapy was given. In Group B, core decompression was performed by drilling a hole (1.2 mm in diameter) from the outer cortex 2.5 cm distal to the proximal end of the greater trochanter. In Group C, 1 multiply 10(7) osteogenically induced ADSCs were resuspended in 0.5 ml PBS, and then injected directly into the femoral head. Femoral head specimens were obtained at postoperative 8 weeks. The bone formation and three-dimensional microstructure of the femoral head was evaluated by micro-computed tomography scans. Immunohistochemical analysis was performed to detect the expression of osteocalcin. Angiogenesis and repair of the femoral head were observed histologically. RESULTS: In trabecular bone at the proximal femur region, the trabecular volume was higher in Group C (130.70 mm(3)+/-4.33 mm(3)) than that in Groups A (101.07 mm(3)+/-7.76 mm(3)) and B (107.89 mm(3)+/-8.68 mm(3), P less than 0.01). Bone volume was significantly increased in Group C (40.09 mm(3)+/-6.35 mm(3)) than in Groups A (29.65 mm(3)+/-4.61 mm(3)) and B (31.80 mm(3)+/-4.01 mm(3), P less than 0.01). The trabecular number was higher in Groups C (1.58+/-0.25) than other two groups (1.15+/-0.18, 1.16+/-0.21, P less than 0.01). Bone mineral density showed statistically significant difference between Groups C and A or B (375.38+/-23.06) mg HA/ccm, vs (313.73+/-19.30) mg HA/ccm and (316.09+/-16.45) mg HA/ccm, P less than 0.01). Histological examination indicated that there was more new bone formation in Group C than in other groups. CONCLUSION: Treatment with autologous osteogeni-cally induced ADSCs transplantation results in an enhanced osteogenesis and microstructure of the vascular deprivation-induced osteonecrosis in rabbits.

Primary study

Unclassified

HGF-transgenic MSCs can improve the effects of tissue self-repair in a rabbit model of traumatic osteonecrosis of the femoral head.

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Authors Wen Q , Jin D , Zhou CY , Zhou MQ , Luo W , Ma L
Journal PloS one
Year 2012
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BACKGROUND: Osteonecrosis of the femoral head (ONFH) is generally characterized as an irreversible disease and tends to cause permanent disability. Therefore, understanding the pathogenesis and molecular mechanisms of ONFH and developing effective therapeutic methods is critical for slowing the progress of the disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study, an experimental rabbit model of early stage traumatic ONFH was established, validated, and used for an evaluation of therapy. Computed tomography (CT) and magnetic resonance (MR) imaging confirmed that this model represents clinical Association Research Circulation Osseous (ARCO) phase I or II ONFH, which was also confirmed by the presence of significant tissue damage in osseous tissue and vasculature. Pathological examination detected obvious self-repair of bone tissue up to 2 weeks after trauma, as indicated by revascularization (marked by CD105) and expression of collagen type I (Col I), osteocalcin, and proliferating cell nuclear antigen. Transplantation of hepatocyte growth factor (HGF)-transgenic mesenchymal stem cells (MSCs) 1 week after trauma promoted recovery from ONFH, as evidenced by a reversed pattern of Col I expression compared with animals receiving no therapeutic treatment, as well as increased expression of vascular endothelial growth factor. CONCLUSIONS/SIGNIFICANCE: These results indicate that the transplantation of HGF-transgenic MSCs is a promising method for the treatment for ONFH and suggest that appropriate interference therapy during the tissue self-repair stage contributes to the positive outcomes. This study also provides a model for the further study of the ONFH etiology and therapeutic interventions.

Primary study

Unclassified

Promotion of bone repair by implantation of cryopreserved bone marrow-derived mononuclear cells in a rabbit model of steroid-associated osteonecrosis.

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Authors Xie XH , Wang XL , He YX , Liu Z , Sheng H , Zhang G , Qin L
Journal Arthritis and rheumatism
Year 2012
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OBJECTIVE: Cytotherapy is an insufficient method for promoting bone repair in steroid-associated osteonecrosis (SAON), and this has been attributed to impairment of the bioactivity of bone marrow-derived stem cells (BMSCs) after pulsed administration of steroids. Cryopreserved autologous bone marrow-derived mononuclear cells (BMMNCs), which contain BMSCs, might maintain their bioactivity in vitro. This study sought to investigate the effects of cryopreserved BMMNCs, before steroid administration, on the enhancement of bone repair in an established rabbit model of SAON. METHODS: For in vitro study, bone marrow was harvested 4 weeks before SAON induction from the iliac crests of rabbits (n = 10) to isolate fresh BMMNCs, and the BMMNCs were then cryopreserved for 8 weeks. Both the fresh and the cryopreserved BMMNCs were evaluated for their bioactivity and osteogenic differentiation capacity. In addition, BMMNCs were isolated 2 weeks after SAON induction and subjected to the same evaluations. For in vivo study, cryopreserved BMMNCs were implanted into the bone tunnel during core decompression of the femur (n = 12 rabbits) after the induction of SAON, and tissue regeneration was evaluated by micro-computed tomography and histologic analyses at 12 weeks postoperation. RESULTS: In vitro, there were no significant differences in the bioactivity or ability to undergo osteogenic differentiation between fresh BMMNCs and cryopreserved BMMNCs, but after SAON induction, both features were decreased significantly. In vivo, the bone mineral density, ratio of bone volume to total volume of bone, and volume and diameter of neovascularization within the bone tunnel were significantly higher in the BMMNC-treated group compared to the nontreated control group at 12 weeks postoperation. CONCLUSION: Cryopreserved BMMNCs maintained their bioactivity and promoted bone regeneration and neovascularization within the bone tunnel after core decompression in this rabbit model of SAON.

Primary study

Unclassified

Adipose-derived stem cells enhance bone regeneration in vascular necrosis of the femoral head in the rabbit.

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Journal The Journal of international medical research
Year 2011
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Osteonecrosis of the femoral head was induced in rabbits by intramuscular injection of methylprednisolone and vascular occlusion of the capital femoral epiphysis by electrocoagulation. Eight weeks later the animals received no treatment (group A), core decompression by drilling a hole (diameter 1.2 mm) from the outer cortex 2.5 cm distal to the proximal end of the greater trochanter (group B), or injection of 10(7) autologous adipose-derived stem cells (ADSCs) directly into the femoral head (group C). Eight weeks later, microcomputed tomography scans indicated that bone and trabecular volume and density were significantly higher in group C than in other groups. Histology indicated more new bone formation in group C than in other groups. Group C showed strong osteocalcin immunoreactivity in subchondral bone osteoblasts in the necrotic femoral head, whereas few osteocalcin-positive cells were found among osteoblasts in other groups. Thus, autologous ADSC transplantation improved osteogenesis and the microstructure of vascular deprivation-induced osteonecrotic tissue.
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