scholarly journals Osteonecrosis of the Femoral Head Safely Healed with Autologous, Expanded, Bone Marrow-Derived Mesenchymal Stromal Cells in a Multicentric Trial with Minimum 5 Years Follow-Up

2021 ◽  
Vol 10 (3) ◽  
pp. 508 ◽  
Author(s):  
Enrique Gómez-Barrena ◽  
Norma Padilla-Eguiluz ◽  
Philippe Rosset ◽  
Philippe Hernigou ◽  
Nicola Baldini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Femoral Head ◽  
Bone Regeneration ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Competent Authority ◽  
First Year ◽  
X Rays ◽  
Advanced Therapy

Background: Osteonecrosis (ON) of the femoral head represents a potentially severe disease of the hip where the lack of bone regeneration may lead to femoral head collapse and secondary osteoarthritis, with serious pain and disability. The aim of this European, multicentric clinical trial was to prove safety and early efficacy to heal early femoral head ON in patients through minimally invasive surgical implantation of autologous mesenchymal stromal cells (MSC) expanded from bone marrow (BM) under good manufacturing practices (GMP). Methods: Twenty-two patients with femoral head ON (up to ARCO 2C) were recruited and surgically treated in France, Germany, Italy and Spain with BM-derived, expanded autologous MSC (total dose 140 million MSC in 7 mL). The investigational advanced therapy medicinal product (ATMP) was expanded from BM under the same protocol in all four countries and approved by each National Competent Authority. Patients were followed during two years for safety, based on adverse events, and for efficacy, based on clinical assessment (pain and hip score) and imaging (X-rays and MRIs). Patients were also reviewed after 5 to 6 years at latest follow-up for final outcome. Results: No severe adverse event was recalled as related to the ATMP. At 12 months, 16/20 per protocol and 16/22 under intention-to-treat (2 drop-out at 3 and 5 months) maintained head sphericity and showed bone regeneration. Of the 4 hips with ON progression, 3 required total hip replacement (THR). At 5 years, one patient (healed at 2 years visit) was not located, and 16/21 showed no progression or THR, 4/21 had received THR (all in the first year) and 1 had progressed one stage without THR. Conclusions: Expanded MSCs implantation was safe. Early efficacy was confirmed in 80% of cases under protocol at 2 years. At 5 years, the overall results were maintained and 19% converted to THR, all in the first year.

COMBINATION THERAPY OF MESENCHYMAL STROMAL CELLS AND INFLIXIMAB IN UNCOMPLICATED (LUMINAL) CROHN DISEASE

2016 ◽  
pp. 24-30
Author(s):  
O. V. Knyazev ◽  
A. G. Konoplyannikov ◽  
A. V. Kagramanova ◽  
S. G. Khomeriki ◽  
N. A. Fadeeva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Combination Therapy ◽  
Mesenchymal Stromal Cells ◽  
Crohn Disease ◽  
Stromal Cells ◽  
Fecal Calprotectin ◽  
Aminosalicylic Acid ◽  
C Reactive Protein ◽  
Reactive Protein

AIMS. To investigate the efficacy of combination therapy using bone marrow-derived mesenchymal stromal cells (MSC) and Infliximab (IFX) to achieve «deep remission» in patients with luminal Crohn disease (CD). METHODS. Our study included 72 patients (19-62 y old) (Ме=29) with luminal CD. Patients ini group (n=21) received standard 5-aminosalicylic acid (5-ASA) and glucocorticosteroids (GCS) therapy in combination with MSC. Patients in 2 group (n=32) were prescribed anti-cytokine therapy IFX. Patients in 3 group (n=19) received MSC and IFX. RESULTS. Clinical, immunobiological and hystological results (C-reactive protein-CRP, fecal calprotectin-FCP, Gebs scale) showed more significant decrease of local and systemic inflammation activity in 3 group of patients. During 3-year follow-up we observed the longer duration of remission in patients, received MSC and IFX compared to 1 group of patients (р=0,04) and 2 group of patients (р=0,038). CONCLUSIONS. Combination therapy of bone marrow-derived MSC and IFL provides «deep remission» in patients with luminal CD and has higher prognostic value in duration of CD remission period.

scholarly journals Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis (phase I)

2021 ◽  
pp. 00773-2020
Author(s):  
Arantza Campo ◽  
José María González-Ruiz ◽  
Enrique Andreu ◽  
Ana B. Alcaide ◽  
María M. Ocón ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Events ◽  
Phase I ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Second Phase ◽  
Endobronchial Administration

RationaleIdiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells have shown benefit in other inflammatory diseases.ObjectivesEvaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF.MethodsA phase-I multicenter clinical Trial (ClinicalTrials.gov:NCT01919827) with a single endobronchial administration of autologous adult BM-MSC in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, 3 patients will be included sequentially in 3 dose cohorts (10×10^6, 50×10^6, and 100×10^6 cells). In a second phase, 9 patients will receive the highest tolerated dose. Follow-up with PFT, 6MWT, and SGRQ were done at 1, 2, 3, 6, and 12 months, and with a computed tomography at 3, 6, and 12 months.FindingsTwenty-one bone marrow samples were obtained from 17 patients. Three patients were excluded for treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSCs infusion. No treatment related severe adverse events were observed during follow-up. Compared to baseline, the mean FVC showed an initial decline of 8.1% at three months. The number of patients without functional progression was 6 (46%) at 3 months and 3 (23%) at 12 months.ConclusionsThe endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous MSCs in IPF patients.

scholarly journals Cell Therapy: Effect of Locally Injected Mesenchymal Stromal Cells Derived from Bone Marrow or Adipose Tissue on Bone Regeneration of Rat Calvarial Defects

2019 ◽  
Vol 9 (1) ◽  
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 Regeneration ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Local Injection ◽  
Expression Of Genes ◽  
Calvarial Defects

Abstract Treatment of large bone defects is a challenging clinical situation that may be benefited from cell therapies based on regenerative medicine. This study was conducted to evaluate the effect of local injection of bone marrow-derived mesenchymal stromal cells (BM-MSCs) or adipose tissue-derived MSCs (AT-MSCs) on the regeneration of rat calvarial defects. BM-MSCs and AT-MSCs were characterized based on their expression of specific surface markers; cell viability was evaluated after injection with a 21-G needle. Defects measuring 5 mm that were created in rat calvaria were injected with BM-MSCs, AT-MSCs, or vehicle-phosphate-buffered saline (Control) 2 weeks post-defect creation. Cells were tracked by bioluminescence, and 4 weeks post-injection, the newly formed bone was evaluated by µCT, histology, nanoindentation, and gene expression of bone markers. BM-MSCs and AT-MSCs exhibited the characteristics of MSCs and maintained their viability after passing through the 21-G needle. Injection of both BM-MSCs and AT-MSCs resulted in increased bone formation compared to that in Control and with similar mechanical properties as those of native bone. The expression of genes associated with bone formation was higher in the newly formed bone induced by BM-MSCs, whereas the expression of genes involved in bone resorption was higher in the AT-MSC group. Cell therapy based on local injection of BM-MSCs or AT-MSCs is effective in delivering cells that induced a significant improvement in bone healing. Despite differences observed in molecular cues between BM-MSCs and AT-MSCs, both cells had the ability to induce bone tissue formation at comparable amounts and properties. These results may drive new cell therapy approaches toward complete bone regeneration.

scholarly journals SP017ONE-YEAR FOLLOW-UP OF A PHASE I CLINICAL TRIAL ON THE USE OF BONE MARROW MESENCHYMAL STROMAL CELLS IN ADPKD PATIENTS

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i92-i92
Author(s):  
Atieh Makhlough ◽  
Soroosh Shekarchian ◽  
Reza Moghadasali ◽  
Seyedeh Esmat Hosseini ◽  
Nasser Aghdami
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Phase I ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Phase I Clinical Trial

scholarly journals Core decompression with bone chips allograft in combination with fibrin platelet-rich plasma and concentrated autologous mesenchymal stromal cells, isolated from bone marrow: results for the treatment of avascular necrosis of the femoral head after 2 years minimum follow-up

2020 ◽  
Vol 30 (2_suppl) ◽  
pp. 3-12
Author(s):  
Martina Rocchi ◽  
Nicoladrea Del Piccolo ◽  
Alessandro Mazzotta ◽  
Gianluca Giavaresi ◽  
Milena Fini ◽  
...  
Keyword(s):  
Femoral Head ◽  
Avascular Necrosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Platelet Rich Plasma ◽  
Core Decompression ◽  
Joint Surface ◽  
Harris Hip Score ◽  
Functional Scores

Introduction: Avascular necrosis of femoral head (AVN) is 1 of the main factors causing disability in young adults. Hip prosthesis can be considered an effective treatment of the painful symptoms but it is a major surgical intervention for this type of population. Thus, a large space should be left to therapeutic alternatives such as regenerative medicine. This retrospective study evaluates 52 AVN treated by core decompression, bone chips allograft, fibrin platelet-rich plasma (PRF) and concentrated autologous mesenchymal stromal cells (MSCs). Methods: The AVN was diagnosed using magnetic resonance imaging (MRI) and graded according to ARCO classification: a patient was classified stage 1 (21 patients), stage 3 (26 patients), and 4 patients were classified as stage 4. We evaluated patients with functional scores (Harris Hip Score) and radiological analysis at 3, 6, 12 and 24 months after the procedure. Patients requiring prosthetic replacement of the joint were included; in these cases, follow-up was interrupted at the time of the joint replacement procedure. Results: Our statistical analysis showed differences between survived and failed treatments, in terms of patient profile and ARCO radiological classification. The best result occurred in patients with ARCO grades 1 and 2, while the more advanced grades showed a high failure rate. It is interesting to note that ARCO quantification, conceived as the joint surface involved in the necrosis, has a negative influence on the outcome of the procedure. Indeed, patients affected by ARCO 3a, where necrosis involved a small portion of the femoral epiphysis and the collapse of the articular surface was limited to 2 mm, showed results similar to those obtained in patients with ARCO 1 and 2. Conclusions: In conclusion, compared with the alternative technique of decompression, our data suggest that post-collapse cases with a small area of necrosis and the use of bone grafts may show better results compared to those of the literature.

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