Autologous Bone Marrow Implantation Research Articles

Bone Disease among Children with Sickle Cell Disease: A Scoping Review of Incidence and Interventions.

Children with sickle cell disease (SCD) are more likely to have deficient serum levels of vitamin D for bone metabolism. However, appropriate interventions are essential to prevent its progression and alleviate symptoms. The aim of this study is to determine interventions for managing bone disease in children with SCD. This study uses a scoping review. A literature review was conducted using PubMed, CINAHL, ScienceDirect, Scopus, and Google Scholar search engines. The study was eligible for inclusion if it included articles published from 2013 to 2023, full-text, and original study design. Study quality was assessed using the Joanna Briggs Institute (JBI) appraisal tool. This review identified six studies and 114 children with SCD, including 57 boys (50%) and 57 girls (50%). The majority of SCD types experienced were HbSS (86.84%), HbS-B0 Thal (7.01%), HbSC (5.27%), and the HbSS Arab-Indian haplotype (0.88%). Bone disease problems that often arise in children with SCD include Avascular Necrosis (AVN) (78.08%), Osteonecrosis of the Femoral Head (ONFH) (18.42%), and other bone problems (3.50%). Meanwhile, four types of intervention findings were used in managing bone disease among children with SCD: 1). Surgical procedures 53 (41.09%) included total hip arthroplasty (THA), Osteotomy, and Multiple epiphyseal drilling with Autologous Bone Marrow Implantation (AMBI); 2). Invasive procedures 67 (51.93%) included intravenous bisphosphonates, hydroxyurea (HU), and core decompression (CD) with bone marrow aspirate concentrate injection: 3). Oral pharmacological or Vitamin D3 (cholecalciferol) 4 (3.10%); 4). Non-pharmacology or physical therapy 5 (3.88%). Our findings highlight that surgical, invasive, pharmacological, and physical therapy interventions positively impact increasing bone mineral density (BMD) and functional improvement of bone disease among children with SCD. The interventions provided excellent functional outcomes with minimal complications and no life-threatening side effects.

Stem cell therapy in early post-traumatic talus osteonecrosis.

Avascular necrosis of the talus is one of the most notable complications associated with talar neck fractures with frequent evolution of the osteonecrosis into a difficult arthrodesis. We tested whether the injection of bone marrow mesenchymal stem cells (MSCs) could improve the repair process of the osteonecrosis. Forty-five early (without collapse) post-traumatic talus osteonecroses (group 1; study group) were treated between 1995 and 2012 with percutaneous injection of progenitor cells (autologous bone marrow concentrate from the iliac crest). The number of MSCs transplanted in each ankle of group 1 was 124 × 103 cells (range 101 × 103 to 164 × 103 cells). The evolution of these osteonecroses treated with autologous bone marrow implantation was compared with the evolution of a control group of 34 talar osteonecroses without collapse and treated with only core decompression (group 2; control group) between 1985 and 1995. The outcome was determined by progression in radiographic stages to collapse, by the need of arthrodesis, and by the time to successfully achieve fusion for patients who needed arthrodesis. For the 45 ankles with autologous concentrate bone marrow grafting, collapse frequency was lower (27%, 12 among 45 versus 71%, 24 among 34; odds ratio 0.1515, 95% CI 0.0563-0.4079; P = 0.0002) and follow-up showed longer duration of survival before collapse or arthrodesis, compared to 34 ankles of the control patients with core decompression alone. Furthermore, the time to successfully achieve fusion after arthrodesis was significantly shorter in patients treated with bone marrow progenitors as compared with the other ankles, which had core decompression alone. In our study the early conservative surgical treatment with autologous bone marrow grafting improved the natural course of the disease as compared with core decompression alone.

Preliminary Results of Multiple Epiphyseal Drilling and Autologous Bone Marrow Implantation for Osteonecrosis of the Femoral Head Secondary to Sickle Cell Disease in Children.

Sickle cell disease (SCD) is the most common cause of osteonecrosis of the femoral head (ONFH) during childhood. The natural history of ONFH in SCD is poor with progression to femoral head collapse and deformity that ultimately may lead to hip osteoarthritis. Multiple epiphyseal drilling with autologous bone marrow implantation may enhance the mechanism of osteogenic repair. The purpose of this study was to describe early clinical and radiographic outcomes in pediatric patients with ONFH secondary to SCD after multiple epiphyseal drilling and AMBI. Nine boys and 2 girls (14 hips) with a mean age of 12.7 years (range, 9.7-18 y) at the time of surgery were evaluated. All patients were followed for at least 1 year after surgery and the mean duration of follow-up was 25 months (range, 12-47 mo). Clinical outcome was assessed by the pain domain from the Children's Hospital Oakland Hip Evaluation Scale and by hip range of motion. The extent of femoral head involvement was assessed by measuring the arc of necrosis and the amount of collapse on anteroposterior and frog lateral radiographs. The University of Pennsylvania system was used to assess the osteonecrosis stage. Wilcoxon signed-rank tests were used to compare radiographic and clinical variables. Compared with preoperative measures, multiple epiphyseal drilling with AMBI resulted in significant improvement in pain (P=0.0010), internal hip rotation (P=0.0005), external hip rotation (P=0.0010), and flexion (P=0.0015). The amount of lateral collapse (P=0.4609), anterior collapse (P=0.4258), and the arc of necrosis (P=0.2251) were not significant after surgery. The majority of the hips had either improvement in the Steinberg stage of disease (4/14 hips) or no further progression (7/14 hips) at the latest follow-up. There were no surgical complications. Multiple epiphyseal drilling with autologous bone marrow cell implantation allows for short-term clinical improvement and limits radiographic progression of ONFH associated with SCD in children with minimal morbidity.

Autologous Implantation of Bone Marrow for Non-Unions and Avascular Necrosis of the Bone.

Introduction: Autologous implantation of bone marrow (BM) stem cells for avascular necrosis of the bone has been previously demonstrated to be feasible and safe procedure. The benefit of using autologous stem cells for bone regeneration consists of avoidance of graft rejection, graft-versus-host disease, and the toxic and infectious complications associated with immunosuppressive regimens.Materials and Methods: We developed an efficient protocol to process autologous BM for volume reduction and mononuclear cell concentration that can be immediately used for autologous implantation. The end-product is a concentrated BM cell suspension that was defined by several parameters as follows: volume, mononuclear cell count, CD34-positive cell count. A total of five patients under general anesthesia underwent BM aspiration, followed by immediate intraoperative BM concentration and implantation at the injured site. Four patients had avascular necrosis of the bone and one had tibia non-union. The patients were followed for one year and monitored clinically and by imaging studies.Results: All five patients treated with autologous bone marrow implantation at the avascular necrosis or non-union site tolerated the procedure well. One year follow-up of these patients reveals improved clinical and functional status. The imaging performed pre and one-year-post procedure revealed no evidence of bone collapse and preserved joint space.Conclusions: Autologous implantation of concentrated bone marrow is a safe and promising treatment for non-unions and avascular necrosis of the bone. Additional studies for further characterization of the concentrated BM used for implantation are in progress.

Clinical Application of Bone Marrow Implantation in Patients With Arteriosclerosis Obliterans, and the Association Between Efficacy and the Number of Implanted Bone Marrow Cells

There have been a number of recent reports on the use of autologous bone marrow implantation (BMI) in the treatment of peripheral arterial disease, with a clinical response rate of approximately 70%. However, the factors that influence efficacy have not yet been clarified. We have analyzed the relationship between the number of implanted bone marrow cells and the clinical efficacy of BMI. Eight patients with arteriosclerosis obliterans were treated with BMI. Bone marrow was aspirated from the ilium (500-1,000 ml), the mononuclear cells were separated and then were implanted. The clinical effectiveness of BMI was evaluated by assessing changes in the ankle-brachial pressure index (ABI) and the transcutaneous oxygen pressure (TcO2) between the pre-treatment baseline, with follow-up testing at 4 weeks. These changes were defined as DeltaABI and DeltaTcO2. The mean number of CD34-positive cells was 1.04+/-0.60 x10(6) /kg body weight. There was a strong correlation between the number of CD34-positive cells and DeltaABI (r=0.754, p=0.028). It is likely that the number of implanted CD34-positive cells is one of the primary factors that influence the clinical efficacy of BMI.

The induction of angiogenesis by the implantation of autologous bone marrow cells: A novel and simple therapeutic method

Background. Bone marrow contains many kinds of primitive cells that could differentiate to endothelial cells and secrete several growth factors. In the current study, we attempted to induce therapeutic angiogenesis by implanting autologous bone marrow cells (BMCs) and using a rat ischemic hind limb model. Methods. BMCs were prepared by removing red blood cells. A rat ischemic hind limb model was made by the ligation of the left femoral artery and its branches. BMCs were injected into 7 points of the ischemic muscles. To assess angiogenesis, a microangiogram, laser Doppler, and histologic evaluation were performed after the surgical procedure. Results. A microangiogram and histologic evaluation showed that angiogenesis was significantly induced in the ischemic hind limb by the implantation of BMCs. Laser Doppler imaging analysis showed that blood flow was significantly increased after implantation of BMCs. Some implanted BMCs were stained positively with CD31 and vascular endothelial-cadherin (VE-cadherin), which might have been incorporated into the vasculature. The condition of ischemia caused an elevation in the level of basic fibroblast growth factor in the ischemic muscle and also in interleukin-1β derived from the implanted BMCs, which might contribute to angiogenesis. Conclusion. These findings indicate that autologous bone marrow implantation may be a novel and simple method for inducing therapeutic angiogenesis. (Surgery 2001;130:44-54.)

Autologous Bone Marrow Implantation Induced Angiogenesis and Improved Deteriorated Exercise Capacity in a Rat Ischemic Hindlimb Model

Background. Bone marrow possesses endothelial progenitor cells that secrete several growth factors and can contribute to the formation of new capillaries. In the present study, we investigated the extent of angiogenesis induced by implantation of autologous bone marrow cells (BMCs) in a rat ischemic hindlimb model and studied whether the increased collateral vessels can improve deteriorated physical function.Materials and methods. Ischemic hindlimb was created by ligation of the femoral artery and its branches in Dark Agouti (DA) rats. BMCs (1 × 107) were injected percutaneously at six points into the gastrocnemius muscle. To assess angiogenesis, histologic evaluation and microangiography were performed at 2 weeks postligation. Severity of the ischemic insult was evaluated by measuring blood flow in the adductor and gastrocnemius muscles using nonradioactive colored microspheres and by determining the femoral arteriovenous oxygen difference (AVDO2) at 2 weeks postligation. Running time on a motor-driven treadmill was used to represent exercise capacity.Results. The histologic evaluation and microangiogram showed that the implanted BMCs induce angiogenesis. Blood flow to the adductor muscle on the treated side in the bone marrow cell implantation (BMI) group was significantly restored to 77.3 ± 19.3% of that of the normally perfused limb in comparison to that in control groups (P < 0.05). AVDO2 in the BMI group significantly decreased when compared with AVDO2 in control groups. Rats in the BMI group ran approximately 1.5 times longer than rats in control groups at 2 and 4 weeks postligation (P < 0.01).Conclusions. Implantation of autologous BMCs induced angiogenesis and improved deteriorated exercise capacity in our rat ischemic hindlimb model.

Autologous Bone-Marrow Implantation after Fast Neutron Irradiation of Dogs

Several investigators have suggested that the course of events leading to death in mice irradiated by fast neutrons involves the gastrointestinal tract. The evidence in support of this position is to be found in the early time of death of neutronirradiated mice (1) and in the experimental observations which showed that bonemarrow implantation is less effective in supporting mice after normally lethal neutron irradiation (2). Studies to determine the LD50 in neutron-irradiated dogs failed to demonstrate an enhanced gastrointestinal component at the lower radiation doses (3); however, the technique of autologous bone-marrow implantation developed by us (4) provides a means for increasing the dose to the animal without causing its death from bone-marrow failure. Under these conditions the gastrointestinal response may be observed while functioning hematopoietic tissue is maintained.