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.

Safety study of autologous adult bone marrow derived mesenchymal stromal cells in idiopathic pulmonary fibrosis - Pilot data

2017 ◽  
Vol 4 (1-4) ◽  
pp. 15-22
Author(s):  
Lakshmi Kiran Chelluri ◽  
Upasna Upadhyay ◽  
Ravindra Nallagonda ◽  
Sudhir Prasad ◽  
Mohammad Samiuddin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Safety Study ◽  
Pilot Data ◽  
Adult Bone Marrow ◽  
Adult Bone

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 Human bone marrow-derived mesenchymal stromal cells cultured in serum-free media demonstrate enhanced antifibrotic abilities via prolonged survival and robust regulatory T cell induction in murine bleomycin-induced pulmonary fibrosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shun Takao ◽  
Taku Nakashima ◽  
Takeshi Masuda ◽  
Masashi Namba ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pulmonary Fibrosis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Pulmonary Inflammation ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Distributed Data ◽  
Serum Free ◽  
Free Media

Abstract Background Mesenchymal stromal cells (MSCs) are a potential therapeutic tool for pulmonary fibrosis. However, ex vivo MSC expansion using serum poses risks of harmful immune responses or unknown pathogen infections in the recipients. Therefore, MSCs cultured in serum-free media (SF-MSCs) are ideal for clinical settings; however, their efficacy in pulmonary fibrosis is unknown. Here, we investigated the effects of SF-MSCs on bleomycin-induced pulmonary inflammation and fibrosis compared to those of MSCs cultured in serum-containing media (S-MSCs). Methods SF-MSCs and S-MSCs were characterized in vitro using RNA sequence analysis. The in vivo kinetics and efficacy of SF-MSC therapy were investigated using a murine model of bleomycin-induced pulmonary fibrosis. For normally distributed data, Student’s t test and one-way repeated measures analysis of variance followed by post hoc Tukey’s test were used for comparison between two groups and multiple groups, respectively. For non-normally distributed data, Kruskal–Wallis and Mann–Whitney U tests were used for comparison between groups, using e Bonferroni’s correction for multiple comparisons. All tests were two-sided, and P < 0.05 was considered statistically significant. Results Serum-free media promoted human bone marrow-derived MSC expansion and improved lung engraftment of intravenously administered MSCs in recipient mice. SF-MSCs inhibited the reduction in serum transforming growth factor-β1 and the increase of interleukin-6 in both the serum and the bronchoalveolar lavage fluid during bleomycin-induced pulmonary fibrosis. SF-MSC administration increased the numbers of regulatory T cells (Tregs) in the blood and lungs more strongly than in S-MSC administration. Furthermore, SF-MSCs demonstrated enhanced antifibrotic effects on bleomycin-induced pulmonary fibrosis, which were diminished by antibody-mediated Treg depletion. Conclusions SF-MSCs significantly suppressed BLM-induced pulmonary inflammation and fibrosis through enhanced induction of Tregs into the lungs and corrected the dysregulated cytokine balance. Therefore, SF-MSCs could be a useful tool for preventing pulmonary fibrosis progression without the demerits of serum use.

scholarly journals P363 Locally injected allogeneic bone marrow-derived mesenchymal stromal cells for the treatment of refractory proctitis: clinical results of a phase IIa trial

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S381-S381
Author(s):  
L Ouboter ◽  
M Barnhoorn ◽  
M van Pel ◽  
J J Zwaginga ◽  
L Hawinkels ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adverse Events ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Experimental Colitis ◽  
Clinical Results ◽  
Fecal Calprotectin ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Mayo Score

Abstract Background Ulcerative proctitis (UP) can be refractory to treatment, which calls for development of new (local) therapies. Local injection of mesenchymal stromal cells (MSCs) has shown beneficial effects in patients with fistulizing Crohn’s disease and promising results have been obtained when MSCs were locally injected in the bowel of mice with experimental colitis. Our primary aim was to determine the safety, feasibility and tolerability of endoscopically injected allogeneic bone marrow-derived MSCs (bmMSCs) in UP patients. Methods UP patients with endoscopic Mayo score (EMS) 2 or 3, who failed on both rectal 5-ASA and corticosteroids for at least 4 weeks, were eligible for inclusion (EudraCT number 2017-003524-75). Rectal therapies were stopped 2 weeks prior to baseline, but other medication was kept stable until at least 6 weeks after MSC injection. MSCs were locally injected in 4 quadrants of the inflamed rectal submucosa if the inflammation was limited to 7 cm. If the length of inflammation was &gt;7 cm, MSCs were injected in another 4 quadrants more proximally as well. Patients in the first cohort (n=7) were treated with 5*106 MSCs/spot and in the second cohort (n=6) with 10*106MSCs/spot. Adverse events, full Mayo score, fecal calprotectin (FCP), histologic activity (Geboes score [GS]) and quality of life (sIBDQ), were assessed at week 0, 2, 6, 12, and 24, and evaluated by non-parametric paired statistical analyses. Results All reported adverse events were minor, no patients required interventions and no feasibility issues were reported. Median[interquartile range (IQR)] full Mayo score was 11[9.5-12] at baseline, 9[8-11] at week 2 (p=0.003), 8[6-10] at week 6 (p=0.001), and 4[1.5-7] at week 24 (p&lt;0.001). The FCP improved in 9/13 patients at week 2, in 6/13 patients at week 6 and in 11/13 patients at week 24 compared to baseline. The EMS at baseline was 3 (n=10 patients) and 2 (n=3 patients) and improved in some patients at week 2 and 6 (NS). At week 24 the EMS was 3 (n=2), 2 (n=4), 1 (n=5) and 0 (n=2)(p=0.002). The median[IQR] GS decreased after 6 weeks (7(6.5-12.5);p=0.09) and 24 weeks (4[2-8];p=0.01) compared to baseline (10[6.5-12.5]). Median[IQR] sIBDQ showed improvement during follow-up; week 2 (45[37.5-52];p=0.1), week 6 (47[42.50-55];p=0.02), week 12 (59[39.50-62];p=0.001) and week 24 (56[44.50-63.50];p=0.001) compared to baseline (41[34-49,50]). No dose- response effects were observed in our study when comparing cohort 1 and 2. Conclusion Local administration of allogeneic bmMSCs appears safe, tolerable and feasible for the treatment of refractory UP, and shows encouraging indications of clinical efficacy. Further mechanistic and immunological analyses are currently being performed.

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.

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