scholarly journals Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients

2009 ◽  
Vol 1 (1) ◽  
pp. 32 ◽  
Author(s):  
Christian Hendrich ◽  
Franz Engelmaier ◽  
Gerhart Waertel ◽  
Rolf Krebs ◽  
Marcus Jäger
Keyword(s):  
Bone Marrow ◽  
Cell Therapy ◽  
Bone Formation ◽  
Ex Vivo ◽  
Bone Marrow Aspiration ◽  
Tumor Formation ◽  
Surveillance Study ◽  
New Bone Formation ◽  
Technical Effort

The clinical application of cellular based therapies with ex vivo cultivation for the treatment of diseases of the musculoskeletal system has until now been limited. In particular, the advanced laboratory and technical effort necessary, regulatory issues as well as high costs are major obstacles. On the other hand, newly developed cell therapy systems permit intra-operative enrichment and application of mesenchymal and progenitor stem cells from bone marrow aspirate concentrate (BMAC) in one single operative session. The objective of the present clinical surveillance study was to evaluate new bone formation after the application of BMAC as well as to record any possible therapy-specific complications For this purpose, the clinical-radiological progress of a total of 101 patients with various bone healing disturbances was documented (surveillance study). The study included 37 necrosis of the head of the femur, 32 avascular necroses/bone marrow edema of other localization, 12 non-unions, 20 other defects. The application of BMAC was performed in the presence of osteonecrosis via a local injection as part of a core decompression (n=72) or by the local adsorption of intra-operative cellular bone substitution material (scaffold) incubated with BMAC during osteosynthesis (n=17) or in further surgery (n=12). After an average of 14 months (2-24 months), the patients were re-examined clinically and radiologically and interviewed. Further surgery was necessary in 2 patients within the follow-up period. These were due to a progression of a collapsed head of the femur with initial necrosis in ARCO Stage III, as well as inadequate new bone formation with secondary loss of correction after periprosthetic femoral fracture. The latter healed after repeated osteosynthesis plus BMAC application without any consequences. Other than these 2 patients, no further complications were observed. In particular, no infections, no excessive new bone formation, no induction of tumor formation, as well as no morbidity due to the bone marrow aspiration from the iliac crest were seen. There were no specific complications within the short follow-up period and a simple intra-operative use of the system for different forms of bone loss could be demonstrated. In the authors’ opinion, the on-site preparation of the bone marrow cells within the operating theater eliminates the specific risk of ex vivo cell proliferation and has a safety advantage in the use of autologous cell therapy for bone regeneration. Additional studies should be completed to determine efficacy.

Abstract 3401: Cell Therapy For Idiophatic Dilated Cardiomyopathy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Antonio C Campos de Carvalho ◽  
Helena F Martino ◽  
Paulo S Oliveira ◽  
Edmilson Assunção ◽  
Rita Vilela ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Oxygen Consumption ◽  
Cell Therapy ◽  
Dilated Cardiomyopathy ◽  
Mononuclear Cells ◽  
Gradient Centrifugation ◽  
Bone Marrow Aspiration ◽  
Functional Class ◽  
Number Of Patients

Given the limited therapeutic options for refractory dilated cardiomyopathy we decided to perform a phase I clinical trial using bone marrow derived mononuclear cells in patients with functional classes II and IV of the NYHA. Inclusion criteria required EF% (Simpson) <35%, VO2 max < 16 kg.ml /min and signed informed consent. After enrollment patients were subject to the following exams at baseline, 2 and 6 months after cell therapy: 12 lead ECG and 24hs holter, echocardiography, chest X-ray, blood biochemistry, BNP, ergoespirometry, MRI and Minnesota Questionnaire. Patients were subject to bone marrow aspiration (80–100 mL) under sedation and local anesthesia and mononuclear cells were obtained after Ficoll gradient centrifugation. A mean of 198 million cells diluted in 20 ml of saline were slowly delivered through catheterization in the coronary arteries (10 ml in LAD, 5 ml in RC, 5 ml in CX). After the procedure patients remained hospitalized for 48hs. We report the results of the first 22 patients that completed the follow-up period. No adverse effects related to the procedure were observed, nor were arrhythmias detected after cell delivery. Four patients died during follow up. For the 18 patients that completed follow up, there was a significant improvement in NYHA functional class and quality of life at 2 and 6 months (p<0.03 and p< 0.007, respectively). There were no statistically significant changes in EF% (18.6%, 18.6% and 19%), EDV (360, 371, 386 ml) or ESV (295, 308, 314 ml) at baseline, 2 and 6 months respectively as measured by MRI. Maximal oxygen consumption showed as significant increase after cell therapy (12.5, 15.3, 16.8 ml/kg.min), and the number of patients with oxygen consumption below the threshold for cardiac transplantation decrease from 75% at baseline to 25% six months after cell therapy. BNP levels were not significantly altered (650, 475, 530 pg/ml). When observed individually, 4 of the 17 patients examined showed an increase in EF% by MRI ≥5%, 7 did not change EF% and 3 decreased EF% by ≥5%. In conclusion, the procedure is safe and feasible but further studies are necessary to test for efficacy.

scholarly journals Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hideki Ueyama ◽  
Yoichi Ohta ◽  
Yuuki Imai ◽  
Akinobu Suzuki ◽  
Ryo Sugama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Structure ◽  
Precursor Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Left Femur

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

scholarly journals The Necessary for Long-Term Follow-up of Mutated Genes and Clonal Evolutions in Multiple Myeloma Combined with cfDNA Assay

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5515-5515
Author(s):  
Yuko Mishima ◽  
Yuji Mishima ◽  
Masahiro Yokoyama ◽  
Noriko Nishimura ◽  
Yoshiharu Kusano ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Genomic Dna ◽  
Research Funding ◽  
Somatic Mutations ◽  
Clinical Course ◽  
Bone Marrow Aspiration ◽  
Long Term Follow Up

Introduction)Somatic mutations in multiple myeloma (MM) are strongly related to the clinical outcome and clonal evolution over the clinical course, and are a major problem. From a clinical viewpoint, although numerous novel drugs have been utilized, achieving long-lasting and complete remission remains difficult. Recent studies have elucidated the mutated genes using next-generation sequencing, and have examined how clonal change can be acquired in myeloma. In this study, we traced the transition of the somatic mutations of bone marrow tumor cells in patients with MM over a long-term follow-up. Furthermore, we compared the somatic mutations found in serum cell-free DNA (cfDNA) and mutated genes obtained from bone marrow myeloma cells. Material and Methods)Patients diagnosed with multiple myeloma who provided written informed consent to participate in the study were enrolled. Patients were treated by immuno-chemotherapy with or without radiation between 2000 and 2017 at our institute. Bone marrow aspiration and biopsy were performed at the time of diagnosis and upon disease progression. Around the time of bone marrow aspiration, serum was obtained from a peripheral blood sample for cfDNA analysis. Myeloma cells were separated from bone marrow samples with MicroBeads of CD138 antibody and genomic DNA was extracted. The peripheral blood samples derived from myeloma patients. The cfDNA was extracted from the serum using a Maxwell RSC cfDNA Plasma kit. Using genomic DNA derived from cfDNA and bone marrow, multiplex polymerase chain reaction (PCR) was performed, and a sequence library was then constructed with an Ion Custom Amplicon panel. The panel for the sequence library was designed using an Ion AmpliSeq DesignerTM. 126 targeted genes were selected. The genomes were sequenced using the Ion ProtonTM System. This protocol was approved by the institutional review board and the Genomic Review Board of the Japanese Foundation for Cancer Research. Result)We followed 7 patients' long term-clinical course and the transition of mutations (8.5 year average). The expression of myeloma driver genes, such as RAS, BRAF, and MYC, were not critical. We did, however, detect a relationship between an increase in the dominant mutated gene, such as TP53, DIS3, FAM46C, KDM6B, and EGR1 and poor prognosis in patients with myeloma. Next, we calculated the cfDNA concentrations from 34 cases. The cfDNA concentrations were significantly higher than 10 control cases (average 62.0 ng/mL (0-200 ng/mL) and 8.18 ng/mL (4.3-14.1 ng/mL), P=0.0046). The 2.5 year-progression free survival (PFS) during the first treatment of MM were tend to be poorer in the group with cfDNA>50 ng/mL (72.9%) than the group with cfDNA<50 ng/mL(25.9%), however there are no statistical significance (P = 0.15).We caluculated concordance rate of derived mutations from bone marrow MM cells and cfDNA in 7 cases. The somatic mutations found in serum cell-free DNA (cfDNA) and bone marrow MM cells were determined the correlation coefficients. However, there are few difference expression pattern in each source. In cfDNA assay, CREEP, EGR1, HDAC4, HDAC6, and JMJD1C were highly expressed as 57.1% (4/7) - 85.7% (6/7), and these results were almost the same as those for bone marrow MM cells. On the other hand, KDM1A (85.7%), PI3KCD (71.4%), and KDM3B (57.1%) were highly detected in cfDNA, although those were not frequently expressed in bone marrow. Discussion)Our data demonstrate the importance of the long-term follow-up of somatic mutations during the clinical course of myeloma. Serum cfDNA is a useful alternative source for detecting somatic mutations in MM patients during long-term follow-up. Disclosures Mishima: Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Yokoyama:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Nishimura:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy; Celgene K.K.: Honoraria. Hatake:Celgene K.K.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; Takeda Pharmaceutical Co.,Ltd.: Honoraria. Terui:Bristol-Myers Squibb K.K.: Research Funding; Bristol-Myers Squibb, Celgene, Janssen, Takeda, MSD, Eisai, Ono, and Chugai-Roche Pharmaceuticals Co.,Ltd.: Honoraria.

scholarly journals New Bone Formation in Tuberculous-Infected Vertebral Body Defect after Administration of Bone Marrow Stromal Cells in Rabbit Model

2016 ◽  
Vol 10 (1) ◽  
pp. 1 ◽  
Author(s):  
Ahmad Jabir Rahyussalim ◽  
Tri Kurniawati ◽  
Nurjati Chairani Siregar ◽  
Agus Syahrurachman ◽  
Ismail Hadisubroto Dilogo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Vertebral Body ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Rabbit Model ◽  
Marrow Stromal Cells ◽  
New Bone Formation

Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Clinical Trial): One Year Follow-Up

2007 ◽  
Vol 16 (9) ◽  
pp. 927-934 ◽  
Author(s):  
Juan C. Chachques ◽  
Jorge C. Trainini ◽  
Noemi Lago ◽  
Osvaldo H. Masoli ◽  
Jose L. Barisani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Extracellular Matrix ◽  
Cell Therapy ◽  
Bone Marrow Cells ◽  
Type I ◽  
Intramyocardial Injection ◽  
Cardiac Wall ◽  
Mononuclear Bone Marrow Cells ◽  
Marrow Cells

Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy the extracellular matrix is deeply altered; therefore, it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. We evaluated intrainfarct cell therapy associated with a cell-seeded collagen scaffold grafted onto infarcted ventricles. In 15 patients (aged 54.2 ± 3.8 years) presenting LV postischemic myocardial scars and with indication for a single OP-CABG, autologous mononuclear bone marrow cells (BMC) were implanted during surgery in the scar. A 3D collagen type I matrix seeded with the same number of BMC was added on top of the scarred area. There was no mortality and no related adverse events (follow-up 15 ± 4.2 months). NYHA FC improved from 2.3 ± 0.5 to 1.4 ± 0.3 (p = 0.005). LV end-diastolic volume evolved from 142 ± 24 to 117 ± 21 ml (p = 0.03), and LV filling deceleration time improved from 162 ± 7 to 196 ± 8 ms (p = 0.01). Scar area thickness progressed from 6 ± 1.4 to 9 ± 1.5 mm (p = 0.005). EF improved from 25 ± 7% to 33 ± 5% (p = 0.04). Simultaneous intramyocardial injection of mononuclear bone marrow cells and fixation of a BMC-seeded matrix onto the epicardium is feasible and safe. The cell-seeded collagen matrix seems to increase the thickness of the infarct scar with viable tissues and helps to normalize cardiac wall stress in injured regions, thus limiting ventricular remodeling and improving diastolic function. Patients' improvements cannot be conclusively related to the cells and matrix due to the association of CABG. Cardiac tissue engineering seems to extend the indications and benefits of stem cell therapy in cardiology, becoming a promising way for the creation of a “bioartificial myocardium.” Efficacy and safety of this approach should be evaluated in a large randomized controlled trial.

Consistent New Bone Formation in 95 Revisions: Average 9-Year Follow-Up

Orthopedics ◽  
2008 ◽  
Vol 31 (7) ◽  
pp. 1-7 ◽  
Author(s):  
George Mantelos ◽  
Panagiotis Koulouvaris ◽  
Hlias Kotsovolos ◽  
Theodoros Xenakis
Keyword(s):  
Bone Formation ◽  
New Bone Formation

scholarly journals Meniscus Repair Outcomes with and without Bone Marrow Aspiration Concentrate

2019 ◽  
Vol 7 (7_suppl5) ◽  
pp. 2325967119S0028 ◽  
Author(s):  
Patrick Allan Massey ◽  
Andrew Zhang ◽  
Christine Bayt Stairs ◽  
Stephen Hoge ◽  
Trevor Carroll ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Aspiration ◽  
Meniscus Repair ◽  
Control Group ◽  
Pain Level ◽  
Average Pain ◽  
The Mean ◽  
One Year ◽  
The One

Objectives: The purpose of the current study is to review the results of meniscus repairs with and without bone marrow aspiration concentrate (BMAC). It is hypothesized that with BMAC, meniscus repair outcomes will be improved when compared to without BMAC at 1 year after surgery. Methods: This is a prospective case control study performed from August 2014 until August 2017. Patients were included if they had a meniscus repair performed with no history of prior meniscus surgery to the operative knee. Patients were excluded if there was a full thickness cartilage tear or International Cartilage Repair Society (ICRS) Grade IV cartilage tear not treated in a single staged surgery. Patients were also excluded if they did not reach the one year follow-up, had a multi-ligamentous knee injury requiring multiple staged procedures. From August 2014 until November 2015, patients had meniscus repair without BMA. Menisci were all repaired arthroscopically using inside-out, outside-in and all-inside techniques. After November 2015, all meniscus repairs were augmented with BMAC. In the BMAC group, all bone marrow was obtained from the ipsilateral femur during the time of surgery. The Biocue BMAC system (Zimmer Biomet, Warsaw Indiana) was used for bone marrow aspiration and BMAC was injected directly into the tear site after repair. Numerical data such as VAS, lysholm and IKDC was analyzed using a 2 sample T-test. Categorical data such as sex, tear location, type of tear and zone of tear were analyzed using a chi-square. Results: A total of 150 patients were initially included in the study. The average age in the control group was 26.3 versus 29.4 in the BMAC group (P=0.27). Thirty seven percent of the control group had an ACL reconstruction versus 40% in the BMAC group (P= .77). The control group improved from an average pain level of 6.1 to 1.2 and the BMAC group improved from an average pain level of 5.9 to 0.7 at the 1 year end point. Both the control group and BMAC group improved with respect to pain with no difference at the 1 year end point (P=.19). There was, however a significantly larger reduction in pain at the 6 week and 3 month time point with BMAC compared to the control group (P=.02 and P=.02 respectively). At the 1-year follow-up, the mean lysholm score improved from 43 to 92 in the control group and 43 to 90 in the BMAC group. The mean IKDC score improved from 37 to 87 in the control group and 36 to 83 in the BMAC group at the one year follow-up. Conclusion: Meniscus repair outcomes were improved at 6 weeks and 3 months post-operatively, when BMAC is used to augment meniscus repair compared to repair without BMAC. Both groups, control group and BMAC meniscus repair group had improved outcomes at 1 year post-operatively with respect to VAS, lysholm and IKDC, with no difference in complication rate.

Effect of cell therapy with osteoblasts differentiated from bone marrow or adipose tissue stromal cells on bone repair

2019 ◽  
Vol 14 (12) ◽  
pp. 1107-1119 ◽  
Author(s):  
Gileade P Freitas ◽  
Helena B Lopes ◽  
Alann T P Souza ◽  
Paula G F P Oliveira ◽  
Adriana L G Almeida ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Bone Formation ◽  
Bone Tissue ◽  
Stromal Cells ◽  
Bone Repair ◽  
Calvarial Bone ◽  
Adipose Tissue Stromal Cells ◽  
Phosphate Buffered Saline

Aim: The aim of this study was to investigate the effect of local injection of osteoblasts differentiated from bone marrow (BM-OB) or adipose tissue (AT-OB) mesenchymal stromal cells on bone tissue formation. Materials & methods: Defects were created in rat calvaria and injected with BM-OB or AT-OB and phosphate-buffered saline without cells were injected as control. Bone formation was evaluated 4 weeks postinjection. Results: Injection of BM-OB or AT-OB resulted in higher bone formation than that obtained with control. The bone tissue induced by cell injections exhibited similar mechanical properties as those of pristine calvarial bone, and its molecular cues suggested the occurrence of a remodeling process. Conclusion: Results of this study demonstrated that cell therapy with osteoblasts induced significant bone formation that exhibited the same quality as that of pre-existent bone.

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