scholarly journals P293 Local Mesenchymal Stem Cells injection in Crohn’s disease strictures: a phase I-II, open-label clinical study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S323-S324
Author(s):  
S Vieujean ◽  
J P Loly ◽  
L Boutaffala ◽  
B Pariente ◽  
C Reenaers ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Crohn’S Disease ◽  
Phase I ◽  
Crohn Disease ◽  
Complete Resolution ◽  
Open Label ◽  
Partial Resolution ◽  
Clinical Scores

Abstract Background Intestinal fibrosis is a common complication of Crohn’s disease (CD) leading to progressive bowel stricture formation. Mesenchymal stem cells (MSCs), known for their immunomodulatory, anti-inflammatory and anti-fibrotic properties, could be a potential therapy in this frequently fibro-inflammatory condition. In this phase I–II open-label pilot trial, we aimed to assess safety and efficacy of local MSCs injection in CD strictures. Methods: CD patients with a non-passable stricture, length from 2 to 5 cm, accessible by ileocolonoscopy, but without intestinal obstruction, fistulas, or abscess, could be included. A total of 3X107 allogenic bone-marrow derived MSCs were equally injected in the 4 quadrants of the strictured bowel wall during an ileocolonoscopy. Adverse events and clinical scores (Crohn Disease Activity Index, Short Health Scale and Crohn Disease Obstructive Score) were evaluated at each follow-up visit (at week 4, 12, 24 and 48) while endoscopy was performed at baseline, W12 and W48. The main judgement criteria for efficacy was the complete (defined by the ability to pass the ileocolonoscope) or partial (defined by a diameter increase) resolution of the stricture at 12 weeks. Other efficacy criteria included complete or partial resolution of the stricture at 48 weeks as well as the evolution of clinical scores between weeks 0, 12 and 48. Results Between 2018 and 2020, we performed 11 local MSCs injections in 10 CD patients (6 female; aged to 38-65 years; median 45 years old; 70% were smoker). The strictures’ (3 primary, 7 anastomotic) location was as follows: 7 at an ileo-colonic or ileo-rectal anastomosis, 1 colonic and 2 of the ileocecal valve. MSCs injections were well tolerated but a total of 5 hospitalizations for occlusion were reported (2 secondary to a different stricture than the injected one) leading to a surgical resection for one patient and an endoscopic dilatation for another one. Neither intestinal perforation nor intra-abdominal fistula or abscess was reported. At 12 weeks, 5 patients (45%) presented a stricture improvement with a complete resolution for 2 and a partial resolution for 3. Of the 11 MSCs injections, 6 patients were re-evaluated at week 48 (2 patients still undergoing follow-up, 1 operated, 1 dilated, and 1 lost to follow-up), 4 patients had a complete resolution and 1 had a partial resolution. The evolution of clinical scores between weeks 0, 12 and 48 (Figure 1) was not statistically significant. Conclusion Local MSCs injection in non-passable CD stricture was well tolerated over the short term but several occlusions were reported in the follow-up. Combining the effects of MSCs with the proven effect of endoscopic balloon dilatation could possibly improve the outcome of CD stricture.

Cell-Based Regenerative Endodontics for Treatment of Periapical Lesions: A Randomized, Controlled Phase I/II Clinical Trial

2020 ◽  
Vol 99 (5) ◽  
pp. 523-529 ◽  
Author(s):  
C. Brizuela ◽  
G. Meza ◽  
D. Urrejola ◽  
M.A. Quezada ◽  
G. Concha ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Phase I ◽  
Umbilical Cord ◽  
Root Canal ◽  
Categorical Variables ◽  
Safety And Efficacy ◽  
Randomized Controlled

A randomized controlled phase I/II clinical trial was designed to evaluate the safety and efficacy of encapsulated human umbilical cord mesenchymal stem cells in a plasma-derived biomaterial for regenerative endodontic procedures (REPs) in mature permanent teeth with apical lesions. The trial included 36 patients with mature incisors, canines, or mandibular premolars showing pulp necrosis and apical periodontitis. Patients were randomly and equally allocated between experimental (REP) or conventional root canal treatment (ENDO) groups. On the first visit, cavity access and mechanical preparation of the root canal were performed. Calcium hydroxide medication was used, and the cavity was sealed. Three weeks later, patients were treated following their assigned protocol of ENDO or REP. Clinical follow-up examinations were performed at 6 and 12 mo. Categorical variables were evaluated by Fisher’s exact test. Quantitative variables were compared using the Mann-Whitney test. The evolution over time of the percentage of perfusion units and the dimensions of lesion and cortical compromise were explored. After the 12-mo follow-up, no adverse events were reported, and the patients showed 100% clinical efficacy in both groups. Interestingly, in the REP group, the perfusion unit percentage measured by laser Doppler flowmetry revealed an increase from 60.6% to 78.1% between baseline and 12-mo follow-up. Sensitivity tests revealed an increase of the positive pulp response in the REP group at 12-mo follow-up (from 6% to 56% on the cold test, from 0% to 28% on the hot test, and from 17% to 50% on the electrical test). We present the first clinical safety and efficacy evidence of the endodontic use of allogenic umbilical cord mesenchymal stem cells encapsulated in a plasma-derived biomaterial. The innovative approach, based on biological principles that promote dentin-pulp regeneration, presents a promising alternative for the treatment of periapical pathology (ClinicalTrials.gov NCT03102879).

Mesenchymal Stem Cell Injection in Crohn’s Disease Strictures: A Phase I–II Clinical Study

2021 ◽  
Author(s):  
Sophie Vieujean ◽  
Jean-Philippe Loly ◽  
Layla Boutaffala ◽  
Paul Meunier ◽  
Catherine Reenaers ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Phase I ◽  
Pilot Trial ◽  
Allogenic Bone ◽  
Clinical Scores ◽  
Anastomotic Strictures ◽  
Stem Cell Injection ◽  
Efficacy Criteria

Abstract Background and Aim Mesenchymal stem cells [MSCs] have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for Crohn’s disease [CD] strictures. In this phase I–II pilot trial, we assessed safety and efficacy of local MSC injection to treat CD strictures. Methods CD patients with a short [less than 5 cm in length] non-passable stricture accessible by ileocolonoscopy were included. Allogenic bone-marrow derived MSCs were injected in the four quadrants of the stricture. Adverse events and clinical scores were evaluated at each follow-up visit and endoscopy and magnetic resonance enterography were performed at baseline, Week [W]12 and W48. The main judgement criterion for efficacy was the complete [defined by the ability to pass the ileocolonoscope] or partial [defined by a diameter increase] resolution of the stricture at W12. Second efficacy criteria included assessment of the stricture at W48 and evolution of clinical scores at W12 and W48. Results We performed 11 MSC injections in 10 CD patients [three primary and seven anastomotic strictures; one stricture injected twice]. MSC injections were well tolerated but four hospitalisations for occlusion were reported. At W12, five patients presented a complete or partial resolution of the stricture [two complete and three partial]. Seven patients were re-evaluated at W48 [one dilated, one operated, and one lost to follow-up] and four patients had a complete resolution. The evolution of clinical scores between W0, W12, and W48 was not statistically significant. Conclusions MSCs injection in CD stricture was well tolerated and may offer a benefit.

Long-Term Follow-Up of Crohn Disease Fistulas After Local Injections of Bone Marrow–Derived Mesenchymal Stem Cells

2015 ◽  
Vol 90 (6) ◽  
pp. 747-755 ◽  
Author(s):  
Rachele Ciccocioppo ◽  
Alessandra Gallia ◽  
Adele Sgarella ◽  
Peter Kruzliak ◽  
Paolo G. Gobbi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Crohn Disease ◽  
Long Term Follow Up ◽  
Local Injections

scholarly journals Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Lan ◽  
Fang Liu ◽  
Lixian Chang ◽  
Lipeng Liu ◽  
Yingchi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aplastic Anemia ◽  
Umbilical Cord ◽  
Pediatric Patients ◽  
Statistical Significance ◽  
Severe Aplastic Anemia ◽  
Control Group ◽  
Open Label ◽  
Cell Counts

Abstract Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).

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