Safety and preliminary efficacy of allogeneic bone marrow-derived multipotent mesenchymal stromal cells for systemic sclerosis: a single-centre, open-label, dose-escalation, proof-of-concept, phase 1/2 study

2022 ◽  
Author(s):  
Dominique Farge ◽  
Séverine Loisel ◽  
Matthieu Resche-Rigon ◽  
Pauline Lansiaux ◽  
Ines Colmegna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Systemic Sclerosis ◽  
Stromal Cells ◽  
Phase 1 ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Allogeneic Bone ◽  
Proof Of Concept ◽  
Single Centre ◽  
Open Label ◽  
Label Dose

scholarly journals Allogeneic Bone Marrow Multipotent Mesenchymal Stromal Cells and Polytrauma Repair: The Role of Fractionated on the Basis of Molecular Mass Red Beetroot Juice in the Prevention of Transplanted Cells Side Effects in Rats

2013 ◽  
Vol 67 (1) ◽  
pp. 52-60
Author(s):  
Dmitrijs Babarikins ◽  
Guntra Krūmiņa ◽  
Irina Paegle ◽  
Diāna Amerika ◽  
Zaiga Krūmiņa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Total Phenolic ◽  
Allogeneic Bone ◽  
Beetroot Juice

Red beetroot (Beta vulgaris) juice (RBJ) is used as a traditional medicine for treatment of anemia. It has been shown that beetroot juice decreases blood pressure, provides a protective effect on blood vessels and has antioxidant and anticancerogenic properties. In the case of polytrauma it might have beneficial effects because of its antioxidant and anti-inflammatory properties as well as antimicrobial activity. It is also well-known that RBR juice can induce undesirable side effects, e.g. flatulent stomach, nausea and other unpleasant reactions. Therefore, it seems prospective to develop red beetroot juice based on its natural compound composition free of undesirable side effects, which could then be used in combination with bone marrow multipotent mesenchymal stromal cells (BM MMSC) transplantation in the case of polytrauma. The aim of the study was to evaluate the therapeutic effect of allogeneic BM MMSC transplantation in rats with experimental polytrauma and to analyse red beetroot fractions separated on the basis of molecular weight in regard to their ingestion impact on cell transplantation efficacy. Red beet juice was fractionated by ultrafiltration (cut-off-point 20 kDa). Total phenolic compound concentration in the final product practically did not decrease. The product was tested in vitro and in vivo. Unlike native juice, fractionated RBJ in vitro suppressed BM MMSC adipogenic (60-71%, P < 0.05) and stimulated osteogenic differentiation (124%, P < 0.05). Experimental polytrauma in rats was modelled by causing three fractures and haemorrhagic shock. Animals were randomised in five groups: 1) normal control; 2) polytrauma; 3) polytrauma + i/v BM MMSC transplantation 36 h and 5 days after surgery; 4) polytrauma + fractionated RBJ administration per os 1ml/d, and 5) polytrauma + BM MMSCs + fractionated RBJ. Transplantation of allogeneic BM MMSCs in rats with experimental polytrauma stimulated bone fracture reparation, but caused plethora in viscera and dystrophic changes in lungs. Combination of BM MMSCs and fractionated RBJ resulted in better bone reparation and significant hematopoiesis stimulation.

scholarly journals AB0370 SAFETY OF CS20AT04, A HAPLOIDENTICAL ALLOGENEIC BONE MARROW-DERIVED MESENCHYMAL STEM CELLS, IN A PHASE 1 STUDY IN LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1485.2-1485
Author(s):  
C. B. Choi ◽  
T. Y. Lee ◽  
K. S. Kim ◽  
S. C. Bae
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Lupus Nephritis ◽  
Dose Escalation ◽  
Phase 1 ◽  
Allogeneic Bone Marrow ◽  
Additional Patient ◽  
Allogeneic Bone ◽  
Dose Limiting Toxicity

Background:Mesenchymal stem cells are known to have immunomodulatory properties and may potentially have therapeutic effect in lupus nephritis. Mesenchymal stem cells form a haploidentical donor are an attractive cell sourceObjectives:CS20AT04, a haploidentical allogeneic bone marrow-derived mesenchymal stem cell, was evaluated in patients with lupus nephritis for safety and tolerability.Methods:This was a single-arm phase 1 dose-escalation trial of CS20AT04 in adult patients with lupus nephritis (NCT03174587). A 3 + 3 design was used for dose escalation. The starting dose was 2.0 x 106 cells/kg and was escalated to 3.0 x 106 cells/kg if there no dose-limiting toxicity. The primary objective was to determine the maximum tolerated dose and evaluate the safety and tolerability at 28 days after the infusion.Results:Seven patients were enrolled in the study. Patients received CS20AT04 through intravenous infusion. The initial dose of 2.0 x 106 cells/kg was administered for the first 3 patients without any dose limiting toxicity. There was 1 patient who were not administered the full 2.0 x 106 cells/kg dose due to technical error during infusion. The patient did not show dose limiting toxicity, but 1 additional patient was enrolled to have 3 patients who received the full 2.0 x 106 cells/kg dose before escalating to the next level dose. The dose of 3.0 x 106 cells/kg was administered for the next 3 patients without any dose limiting toxicity. Three adverse events were reported (1 diarrhea, 1 toothache, and 1 arthralgia) and they were all NCI-CTC grade I events.Conclusion:CS20AT04 was well tolerated in single dose up to 3.0 x 106 cells/kg in patients with lupus nephritis.Acknowledgments:This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C0778).Disclosure of Interests:Chan-Bum Choi: None declared, Tae Yong Lee Shareholder of: Corestem Inc, Employee of: Corestem Inc, Kyung Suk Kim Shareholder of: Corestem Inc, Employee of: Corestem Inc, Sang-Cheol Bae: None declared

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