Safety and efficacy of clinical-grade, cryopreserved menstrual blood mesenchymal stromal cells in experimental acute respiratory distress syndrome.

Autor:	Alcayaga-Miranda F; Laboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile.; Consorcio Regenero, Chilean Consortium for Regenerative Medicine, Santiago, Chile.; Cells for Cells, Santiago, Chile.; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile., Dutra Silva J; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Parada N; Laboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile., Andrade da Silva LH; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Ferreira Cruz F; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil., Utreras Y; Laboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile., Hidalgo Y; Laboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile.; Consorcio Regenero, Chilean Consortium for Regenerative Medicine, Santiago, Chile.; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile., Cádiz MI; Laboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile.; Consorcio Regenero, Chilean Consortium for Regenerative Medicine, Santiago, Chile.; Cells for Cells, Santiago, Chile., Tapia Limonchi R; Consorcio Regenero, Chilean Consortium for Regenerative Medicine, Santiago, Chile.; Cells for Cells, Santiago, Chile., Espinoza F; Cells for Cells, Santiago, Chile.; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile., Bruhn A; Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile., Khoury M; Laboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile.; Consorcio Regenero, Chilean Consortium for Regenerative Medicine, Santiago, Chile.; Cells for Cells, Santiago, Chile.; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile., R M Rocco P; Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil., Cuenca J; Laboratory of Nano-Regenerative Medicine, Centro de Investigación e Innovación Biomédica (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile.; Consorcio Regenero, Chilean Consortium for Regenerative Medicine, Santiago, Chile.; Cells for Cells, Santiago, Chile.; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2023 Jan 30; Vol. 11, pp. 1031331. Date of Electronic Publication: 2023 Jan 30 (Print Publication: 2023).
DOI:	10.3389/fcell.2023.1031331
Abstrakt:	Background: Treatment for critical care conditions, such as acute respiratory distress syndrome (ARDS), requires ready-to-administer injectable mesenchymal stromal cells (MSCs). A validated cryopreserved therapy based on MSCs derived from menstrual blood (MenSCs) is an attractive option that offers advantages over freshly cultured cells and allows its use as an off-the-shelf therapy in acute clinical conditions. The main goal of this study is to provide evidence on the impact of cryopreservation on different biological functions of MenSCs and to determine the optimal therapeutic dose, safety, and efficacy profile of clinical-grade, cryopreserved (cryo)-MenSCs in experimental ARDS. Methods: Biological functions of fresh versus cryo-MenSCs were compared in vitro . The effects of cryo-MenSCs therapy were evaluated in vivo in ARDS-induced ( Escherichia coli lipopolysaccharide) C57BL/6 mice. After 24 h, the animals were treated with five doses ranging from 0.25×10 5 to 1.25×10 6 cells/animal. At 2 and 7 days after induction of ARDS, safety and efficacy were evaluated. Results: Clinical-grade cryo-MenSCs injections improved lung mechanics and reduced alveolar collapse, tissue cellularity, and remodelling, decreasing elastic and collagen fiber content in alveolar septa. In addition, administration of these cells modulated inflammatory mediators and promoted pro-angiogenic and anti-apoptotic effects in lung-injured animals. More beneficial effects were observed with an optimal dose of 4×10 6 cells/Kg than with higher or lower doses. Conclusion: From a translational perspective, the results showed that clinical-grade cryopreserved MenSCs retain their biological properties and exert a therapeutic effect in mild to moderate experimental ARDS. The optimal therapeutic dose was well-tolerated, safe, and effective, favouring improved lung function. These findings support the potential value of an off-the-shelf MenSCs-based product as a promising therapeutic strategy for treating ARDS. Competing Interests: MK is the chief science officer of Cells for Cells and Consorcio Regenero. FE is the medical director of Cells for Cells. JC and FA-M received stipends from Cells for Cells. The other authors declare no competing interests. (Copyright © 2023 Alcayaga-Miranda, Dutra Silva, Parada, Andrade da Silva, Ferreira Cruz, Utreras, Hidalgo, Cádiz, Tapia Limonchi, Espinoza, Bruhn, Khoury, R. M. Rocco and Cuenca.)
Databáze:	MEDLINE
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