Autologous Bone Marrow Mesenchymal Cells Research Articles

Randomized clinical trial: expanded autologous bone marrow mesenchymal cells combined with allogeneic bone tissue, compared with autologous iliac crest graft in lumbar fusion surgery

BACKGROUND CONTEXTAlthough autogenous iliac crest bone graft (AICBG) is considered the gold-standard graft material for spinal fusion, new bone substitutes are being developed to avoid associated complications and disadvantages. By combining autologous bone marrow mesenchymal stromal cells (MSCs) expanded ex vivo and allogenic cancellous bone graft, we obtain a tissue-engineered product that is osteoconductive and potentially more osteogenic and osteoinductive than AICBG, owing to the higher concentration of MSCs. PURPOSEThis study aimed to evaluate the feasibility and safety of implanting a tissue-engineered product consisting of expanded bone marrow MSCs loaded onto allograft bone (MSC+allograft) for spinal fusion in degenerative spine disease, as well as to assess its clinical and radiological efficacy. STUDY DESIGN/SETTINGA prospective, multicenter, open-label, blinded-reader, randomized, parallel, single-dose phase I-II clinical trial. PATIENT SAMPLEA total of 73 adult patients from 5 hospitals, with Meyerding grade I-II L4–L5 degenerative spondylolisthesis and/or with L4–L5 degenerative disc disease who underwent spinal fusion through transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURESSpinal fusion was assessed by plain X-ray at 3, 6, and 12 months and by computed tomography (CT) at 6 and 12 months post-treatment. An independent radiologist performed blinded assessments of all images. Clinical outcomes were measured as change from baseline value: visual analog scale for lumbar and sciatic pain at 12 days, 3, 6, and 12 months posttreatment, and Oswestry Disability Index and Short Form-36 at 3, 6, and 12 months posttreatment. METHODSPatients who underwent L4–L5 TLIF were randomized for posterior graft type only, and received either MSC+allograft (the tissue-engineered product, group A) or AICBG (standard graft material, group B). Standard graft material was used for anterior fusion in all patients. Feasibility was measured primarily as the percentage of randomized patients who underwent surgery in each treatment group. Safety was assessed by analyzing treatment-emergent adverse events (AEs) for the full experimental phase and appraising their relationship to the experimental treatment. Outcome measures, both radiological and clinical, were compared between the groups. RESULTSSeventy-three patients were randomized in this study, 36 from the MSC+allograft group and 37 from the AICBG group, and 65 were surgically treated (31 group A, 34 group B). Demographic and comorbidity data showed no difference between groups. Most patients were diagnosed with grade I or II degenerative spondylolisthesis. MSC+allograft was successfully implanted in 86.1% of randomized group A patients. Most patients suffered treatment-emergent AEs during the study (88.2% in group A and 97.1% in group B), none related to the experimental treatment. X-ray-based rates of posterior spinal fusion were significantly higher for the experimental group at 6 months (p=.012) and 12 months (p=.0003). CT-based posterior fusion rates were significantly higher for MSC+allograft at 6 months (92.3% vs 45.7%; p=.0001) and higher, but not significantly, at 12 months (76.5% vs 65.7%; p=.073). CT-based complete response (defined as the presence of both posterior intertransverse fusion and anterior interbody fusion) was significantly higher at 6 months for MSC+allograft than for AICBG (70.6% vs 40%; p=.0038), and remained so at 12 months (70.6% vs 51.4%; p=.023). Clinical results including patient-reported outcomes improved postsurgery, although there were no differences between groups. CONCLUSIONSCompared with the current gold standard, our experimental treatment achieved a higher rate of posterior spinal fusion and radiographic complete response to treatment at 6 and 12 months after surgery. The treatment clearly improved patient quality of life and decreased pain and disability at rates similar to those for the control arm. The safety profile of the tissue-engineered product was also similar to that for the standard material, and no AEs were linked to the product. Procedural AEs did not increase as a result of BM aspiration. The use of expanded bone marrow MSCs combined with cancellous allograft is a feasible and effective technique for spinal fusion, with no product-related AEs found in our study.

Autologous Bone Marrow Mesenchymal Cell Transplantation in the Treatment of Freiberg's Disease: Case Report

Background: Osteonecrosis of the metatarsal head, classically known as Freiberg's disease, presents as aseptic necrosis of the epiphysis of undefined etiology, although it may be associated with trauma, prolonged corticotherapy or systemic diseases such as sickle cell disease. There are several techniques described for the treatment of osteonecrosis secondary to sickle cell disease. Methods: Case report and the surgical description of the use of autologous bone marrow mesenchymal stem cell transplantation for the treatment of osteonecrosis of the 2nd metatarsal head. Results: Nuclear magnetic resonance imaging performed after one year of follow-up showed a regression of the findings found in the preoperative evaluation. Conclusion: This is the first time that the technique of autologous bone marrow mesenchymal stem cell implantation has been employed for the treatment of osteonecrosis of the metatarsal head. The case reported shows that the technique is safe and brings good results after conservative treatment failure.

218. Randomized prospective clinical trial to evaluate efficacy and safety in lumbar fusion surgery of implantation of autologous bone marrow mesenchymal cells expanded ex vivo and combined with allogeneic bone tissue, compared with autologous iliac crest graft: part I: radiological findings

BACKGROUND CONTEXT Spinal fusion is a widely used surgical technique for a great variety of spine pathologies. Spinal fusion using the patient's iliac crest is the standard surgical technique, although it is associated with a relevant percentage of failures and local morbidity of the bone donor area. PURPOSE The main objective of this clinical trial was to evaluate the feasibility, safety, and efficacy of implantation of a scaffold of heterologous human cancellous bone tissue seeded with autologous bone marrow mesenchymal cells expanded ex vivo (XCEL-MT-OSTEO-ALPHA) and to compare the resulting intervertebral fusion as evaluated by radiography and computed tomography (CT) with that obtained in patients who received autologous iliac crest graft. STUDY DESIGN/SETTING Multicenter, prospective, open-label, randomized, parallel and single-dose phase I-II study (EudraCT No.2010-023999-12; NCT01552707). PATIENT SAMPLE Sixty-five patients from 5 centers (mean age, 61.05 years; 65.6% female) with degenerative spondylolisthesis (79.4%) and/or disc disease at L4-L5. OUTCOME MEASURES Adverse events were recorded and fusion was assessed by radiography (3, 6, and 12 months) and CT (6 and 12 months). Bone fusion status was evaluated according to previously established qualitative criteria by a radiologist who was blind to treatment allocation. METHODS Patients underwent instrumented circumferential fusion at L4-L5; transforaminal lumbar interbody fusion (TLIF) was performed using an intersomatic cage filled with autologous iliac crest graft, and intertransverse fusion consisted of local bone graft on the TLIF side and randomly assigned XCEL-MT-OSTEO-ALPHA (Group A, treatment) or autologous iliac crest graft (Group B, control) on the contralateral side.Patients underwent follow-up for 1 year. RESULTS Groups A and B comprised 31 and 34 patients, respectively. There were no significant differences in preoperative variables between groups, and no serious adverse reactions were associated with the product. Compared with controls the treatment group showed a significantly higher rate of intertransverse fusion as determined by radiography at 3 (85.7% vs 56.3%), 6 (81.5% vs 48.3%), and 12 months (96.3% vs 51.7%) and by CT at 6 months (96.3% vs 54.8%). One year after surgery the intertransverse fusion rate was higher in the treatment than the control group (86.2% vs 66.7%), although this difference was not significant. CONCLUSIONS XCEL-MT-OSTEO-ALPHA is a viable and safe product for use in lumbar fusion surgery. Radiological fusion rates in the area in which the product was applied were significantly higher than those obtained with autologous iliac crest graft. FDA DEVICE/DRUG STATUS XCEL-MT-OSTEO-ALPHA (Not approved for this indication)

P136. Randomized, prospective clinical trial to evaluate efficacy and safety in lumbar fusion surgery of implantation of autologous bone marrow mesenchymal cells expanded ex vivo and combined with allogeneic bone tissue, compared with autologous iliac crest graft; part II: clinical findings

P136. Randomized, prospective clinical trial to evaluate efficacy and safety in lumbar fusion surgery of implantation of autologous bone marrow mesenchymal cells expanded ex vivo and combined with allogeneic bone tissue, compared with autologous iliac crest graft; part II: clinical findings

Intra-articular injection of expanded autologous bone marrow mesenchymal cells in moderate and severe knee osteoarthritis is safe: a phase I/II study

BackgroundKnee osteoarthritis (KOA) is a major health problem especially in the aging population. There is a need for safe treatment that restores the cartilage and reduces the symptoms. The use of stem cells is emerging as a possible option for the moderate and severe cases. This study aimed at testing the safety of autologous bone marrow mesenchymal stem cells (BM-MSCs) expanded in vitro when given intra-articularly to patients with stage II and III KOA. As a secondary end point, the study tested the ability of these cells to relieve symptoms and restore the knee cartilage in these patients as judged by normalized knee injury and Osteoarthritis Outcome Score (KOOS) and by magnetic resonance imaging (MRI).MethodsThirteen patients with a mean age of 50 years suffering from KOA stages II and III were given two doses of BM-MSCs 1 month apart totaling 61 × 106 ± 0.6 × 106 by intra-articular injection in a phase I prospective clinical trial. Each patient was followed for a minimum of 24 months for any adverse events and for clinical outcome using normalized KOOS. Cartilage thickness was assessed by quantitative MRI T2 at 12 months of follow-up.ResultsNo severe adverse events were reported up to 24 months follow-up. Normalized KOOS improved significantly. Mean knee cartilage thickness measured by MRI improved significantly.ConclusionBM-MSCs given intra-articularly are safe in knee osteoarthrosis. Despite the limited number of patients in this study, the procedure described significantly improved the KOOS and knee cartilage thickness, indicating that they may enhance the functional outcome as well as the structural component.Trial registrationClinicalTrials.gov, NCT02118519

Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).

Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis.

Autologous bone marrow mesenchymal cell induced chondrogenesis for the treatment of osteoarthritis of knee.

Supplementary material is available for this article at 10.1007/s13770-016-9125-y and is accessible for authorized users.

RGD-Conjugated Copolymer Incorporated into Composite of Poly(lactide-co-glycotide) and Poly(l-lactide)-Grafted Nanohydroxyapatite for Bone Tissue Engineering

Various surface modification methods of RGD (Arg-Gly-Asp) peptides on biomaterials have been developed to improve cell adhesion. This study aimed to examine a RGD-conjugated copolymer RGD/MPEG-PLA-PBLG (RGD-copolymer) for its ability to promote bone regeneration by mixing it with the composite of poly(lactide-co-glycotide) (PLGA) and hydroxyapatite nanoparticles surface-grafted with poly(L-lactide) (g-HAP). The porous scaffolds were prepared using solvent casting/particulate leaching method and grafted to repair the rabbit radius defects after seeding with autologous bone marrow mesenchymal cells (MSCs) of rabbits. After incorporation of RGD-copolymer, there were no significant influences on scaffold's porosity and pore size. Nitrogen of RGD peptide, and calcium and phosphor of g-HAP could be exposed on the surface of the scaffold simultaneously. Although the cell viability of its leaching liquid was 92% that was lower than g-HAP/PLGA, its cell adhesion and growth of 3T3 and osteoblasts were promoted significantly. The greatest increment in cell adhesion ratios (131.2-157.1% higher than g-HAP/PLGA) was observed when its contents were 0.1-1 wt % but only at 0.5 h after cell seeding. All the defects repaired with the implants were bridged after 24 weeks postsurgery, but the RGD-copolymer contained composite had larger new bone formation and better fusion interface. The composites containing RGD-copolymer enhanced bone ingrowth but presented more woven bones than others. The combined application of RGD-copolymer and bone morphological protein 2 (BMP-2) exhibited the best bone healing quality and was recommended as an optimal strategy for the use of RGD peptides.

Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees

To investigate the effectiveness of autologous culture-expanded bone marrow mesenchymal cell transplantation for repairing articular cartilage defects, we transplanted autologous culture-expanded bone marrow mesenchymal cells into nine full-thickness articular cartilage defects of the patello-femoral joints (including two kissing lesions) in the knees of three patients, a 31 year-old female, a 44 year-old male and a 45 year-old male. Three weeks before transplantation, bone marrow blood was aspirated from the iliac crest. Adherent cells were cultured with media containing autologous serum. Single-passaged cells were collected, embedded in a collagen solution (5 x 10(6) cells/ml), placed on a collagen sheet, gelated, transplanted into the defect and covered with autologous periosteum or synovium. Six months after transplantation, the patients' clinical symptoms had improved and the improvements have been maintained over the follow-up periods (17-27 months). Histology of the first patient 12 months after the transplantation revealed that the defect had been repaired with the fibrocartilaginous tissue. Magnetic resonance imaging of the second patient 1 year after transplantation revealed complete coverage of the defect, but we were unable to determine whether or not the material that covered the defects was hyaline cartilage. Autologous bone marrow mesenchymal cells transplantation may be an effective approach to promote the repair of articular cartilage defects.

Articular cartilage regeneration

The main functions of articular cartilages are load-bearing and reducing friction of the articular surfaces. Because the capacity of articular cartilage to repair is limited, many attempts have been made to repair articular cartilage defects, which include transplantations of various tissues or cells. Within them, autologous cultured chondrocyte or autologous bone marrow mesenchymal cell transplantations are reported to be useful methods to repair articular cartilage defects. Here, we introduce these methods of tissue engineering and gene therapy, which are expected to become new treatments of articular cartilage defects.