Dataset Information

The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs.

ABSTRACT: This study aimed to investigate if autologous bone marrow mesenchymal stem cells (MSCs) could treat osteonecrosis of the femoral head (ONFH) and what the fate and distribution of the cells are in dogs. Twelve Beagle dogs were randomly divided into two groups: MSCs group and SHAM operated group. After three weeks, dogs in MSCs group and SHAM operated group were intra-arterially injected with autologous MSCs and 0.9% normal saline, respectively. Eight weeks after treatment, the necrotic volume of the femoral heads was significantly reduced in MSCs group. Moreover, the trabecular bone volume was increased and the empty lacunae rate was decreased in MSCs group. In addition, the BrdU-positive MSCs were unevenly distributed in femoral heads and various vital organs. But no obvious abnormalities were observed. Furthermore, most of BrdU-positive MSCs in necrotic region expressed osteocalcin in MSCs group and a few expressed peroxisome proliferator-activated receptor-? (PPAR-?). Taken together, these data indicated that intra-arterially infused MSCs could migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. It suggests that intra-arterial infusion of autologous MSCs might be a feasible and relatively safe method for the treatment of femoral head necrosis.

SUBMITTER: Jin H

PROVIDER: S-EPMC4686726 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs.

Jin Hongting H Xu Taotao T Chen Qiqing Q Wu Chengliang C Wang Pinger P Mao Qiang Q Zhang Shanxing S Shen Jiayi J Tong Peijian P

Stem cells international 20151208

This study aimed to investigate if autologous bone marrow mesenchymal stem cells (MSCs) could treat osteonecrosis of the femoral head (ONFH) and what the fate and distribution of the cells are in dogs. Twelve Beagle dogs were randomly divided into two groups: MSCs group and SHAM operated group. After three weeks, dogs in MSCs group and SHAM operated group were intra-arterially injected with autologous MSCs and 0.9% normal saline, respectively. Eight weeks after treatment, the necrotic volume of ...[more]

PMID: 26779265

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Project description:BACKGROUND:Osteonecrosis of the femoral head (ONFH) is a frequent orthopedic disease leading to destruction of the hip joint and disabling arthritis. Several procedures have been developed to treat the joint deterioration in case of osteonecrosis, trying to avoid or delay an intervention of total hip replacement, especially in young patients. The aim of this study was to analyze the use of autologous bone micrografts derived from cancellous bone in the management of avascular ONFH. The treatment described was implemented using the Rigenera® protocol to obtain autologous micrografts: small fragments of cancellous bone collected by femoral neck, disaggregated and injected in the necrotic area using an empty screw. MATERIALS AND METHODS:Twenty adult patients affected by avascular ONFH were enrolled in this study; all patients reported a preoperative intermittent coxo-arthrosis and limited function of intra and extra rotation of the hip. Inclusion criteria were an Oxford Hip Score between (OHS) 20 and 39, a Harris hip score (HHS) showing pre-operative poor results (lower than 70 points) and a stage II-IIIA and IIIB according with the classification proposed by the Association Research Circulation Osseous (ARCO). RESULTS:Using an MRI evaluation, after six months, the authors observed a complete regression of necrotic area and the restoration of osseous structure. Clinical outcome has been evaluated at 6-12 and 24 months follow-up. At the final F.U. the HHS rised from poor to good results (mean value at final F.U of 84) while the OHS improved significantly already after 21 days from micrografts injection (mean 35.4 ± 7.5) with an increasing trend until to two-year final FU (mean 37.4 ± 9.5). The full recovery of daily and mild sport activities was reached after 20 and 90 days from intervention, respectively. CONCLUSION:The results of this study are suggestive for a new approach in the treatment of avascular ONFH assuming a process of bone regeneration based on a dual mechanism of action, biological and mechanical, induced by micrografts and injected using an empty screw as vehicle.

Project description:Study designSystematic Review.ObjectivesWe performed this systematic overview on the overlapping meta-analyses that analyzed autologous bone marrow-derived mesenchymal stem cell(BM-MSC) therapy along with core decompression(CD) for the management of osteonecrosis of the femoral head(ONFH) and identify which study provides the current best evidence on the topic and generate recommendations for the same.Materials and methodsWe conducted independent and duplicate electronic database searches in PubMed, Web of Science, Embase, Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects till September 2020 for meta-analyses that analyzed the efficacy of BM-MSC therapy along with CD for ONFH. Methodological quality assessment was made using Oxford Levels of Evidence, AMSTAR scoring, and AMSTAR 2 grades. We then utilized the Jadad decision algorithm to identify the study with the highest quality to represent the current best evidence to generate the recommendation.Results6 meta-analyses fulfilling the eligibility criteria were included. The AMSTAR scores of the included studies varied from 4 to 9 (mean:7) and all the included studies had critically low reliability in their summary of results due to their methodological flaws according to AMSTAR 2 grades. The current best evidence showed that utilization of BM-MSC therapy along with CD for ONFH resulted in significant improvement in Harris hip scores at 12 and 24 months along with a significant reduction in the necrotic area of the femoral head and the rate of conversion to total hip arthroplasty(THA) without a significant rise in adverse events due to the procedure.ConclusionBased on this systematic overview, we give a Level II recommendation that BM-MSC therapy is more efficacious along with CD in the management of ONFH compared to CD alone. BM-MSC therapy provides better pain relief with significant functional improvement and delaying the collapse of the femoral head thereby preventing further treatment such as THA.

Project description:BackgroudOutcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH.MethodsEighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint.ResultsPreoperatively, the necrotic lesion extent was 63.0% (38.4%-96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2).ConclusionsOur outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.

Project description:The objective of this study was to determine the benefits of combination treatment with mechanical support and targeted intra-arterial infusion of peripheral blood stem cells (PBSCs) mobilized by granulocyte-colony stimulating factor (G-CSF) via the medial circumflex femoral artery on the progression of osteonecrosis of the femoral head (ONFH). Fifty-five patients (89 hips) with early and intermediate stage ONFH were recruited and randomly assigned to combination treatment or mechanical support treatment (control group). All hips received mechanical support treatment (porous tantalum rod implantation). Then, hips in the combination treatment group were performed targeted intra-arterial infusion of PBSCs. At each follow-up, Harris hip score (HHS) and Association Research Circulation Osseous (ARCO) classification were used to evaluate the symptoms and progression of osteonecrosis. Total hip arthroplasty (THA) was assessed as an endpoint at each follow-up. At 36 months, 9 of the 41 hips (21.95%) in the control group progressed to clinical failure and underwent THA whereas only 3 of the 48 hips (6.25%) in the combination treatment group required THA (p?=?0.031). Kaplan-Meier survival analysis showed a significant difference in the survival time between the two groups (log-rank test; p?=?0.025). Compared to the control group, combination treatment significantly improved the HHS at 36 months (p?=?0.003). At the final follow-up examination, radiological progression was noted in 13 of 41 hips (31.71%) for the control group, but in only 4 of 48 hips (8.33%) for the combination treatment group (p?=?0.005). The overall collapse rates were 15.15% (5/33 hips) and 8.11% (3/37 hips) in the control and combination treatment groups, respectively. Targeted intra-arterial infusion of PBSCs is capable of enhancing the efficacy of biomechanical support in the treatment of ONFH. This clinical trial confirmed that the combination treatment might be a safe and feasible choice for the treatment of early or intermediate stages of ONFH.

Project description:BackgroundGlucocorticoid usage and alcohol abuse are the most widely accepted risk factors for nontraumatic osteonecrosis of femoral head (ONFH). Despite distinct etiologies between glucocorticoid-associated ONFH (GONFH) and alcohol-associated ONFH (AONFH), little is known about the differences of the microarchitectural and histomorphologic characteristics between these subtypes of ONFH.PurposesTo investigate bone microarchitecture, bone remodeling activity and histomorphology characteristics of different regions in femoral heads between GONFH and AONFH.MethodsFrom September 2015 to October 2020, 85 patients diagnosed with GONFH and AONFH were recruited. Femoral heads were obtained after total hip replacement. Femoral head specimens were obtained from 42 patients (50 hips) with GONFH and 43 patients (50 hips) with AONFH. Micro-CT was utilized to assess the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology was subsequently performed to evaluate histopathological alterations and bone remodeling levels.ResultsIn the necrotic region, most of the microarchitectural parameters did not differ significantly between GONFH and AONFH, whereas both the reactive interface and normal region revealed a less sclerotic microarchitecture but a higher bone remodeling level in GONFH than AONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GONFH.ConclusionsGONFH and AONFH shared similar microarchitecture and histopathological features in the necrotic region, while GONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region. These differences between GONFH and AONFH in bone microarchitectural and histopathological characteristics might contribute to the development of disease-modifying prevention strategies and treatments for ONFH, taking into etiologies.

Project description:(1) Background: Osteonecrosis of the femoral head (ONFH) is characterized by impaired vascularization with ischemia resulting in bone cell death, leading to the deterioration of the hip joint. Mesenchymal stem/stromal cells (MSCs) are an attractive potential therapeutic approach in this setting. The aim of this study is to evaluate the clinical improvement in terms of pain and quality of life, as well as the safety of the procedure during the follow-up of patients. (2) Methods: A Phase I-II Open-Label Non-Randomized Prospective clinical trial was conducted. Eight patients with idiopathic ONFH and stage < IIC in the ARCO classification were included. Four weeks before therapy, 40 mL of autologous bone marrow was obtained, and MSCs were expanded under Good-Manufacturing-Practice (GMP) standards. Study medication consisted of a suspension of autologous BM-derived MSCs (suspended in a solution of 5-10 mL of saline and 5% human albumin) in a single dose of 0.5-1 × 106 cells/kg of the patient, administered intraosseously with a trocar and under radioscopic control. Per-protocol monitoring of patients included a postoperative period of 12 months, with a clinical and radiological assessment that included the visual analog scale (VAS), the Harris scale, the SF-36, and the radiological evolution of both hips. In addition, all patients were further followed up for eight years to assess the need for long-term total hip replacement (THR) surgery. (3) Results: Median age of patients included was 48.38 ± 7.38 years, and all patients were men. Autologous MSCs were expanded in all cases. There were no adverse effects related to cell administration. Regarding efficacy, both VAS and ODI scores improved after surgery. Radiologically, 12.5% of patients improved at the end of follow-up, whereas 50% improved clinically. No adverse effects related to the procedure were recorded, and none of the patients needed THR surgery within the first year after MSC therapy. (4) Conclusions: The use of autologous MSCs for patients with ONFH disease is feasible, safe in the long term, and potentially effective.

Dataset Information

The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs.

Publications

The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs.

Similar Datasets

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