AUTHOR=Alcayaga-Miranda Francisca , Dutra Silva Johnatas , Parada Nicol , Andrade da Silva Luisa Helena , Ferreira Cruz Fernanda , Utreras Yildy , Hidalgo Yessia , Cádiz María Ignacia , Tapia Limonchi Rafael , Espinoza Francisco , Bruhn Alejandro , Khoury Maroun , R. M. Rocco Patricia , Cuenca Jimena 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1031331

DOI=10.3389/fcell.2023.1031331

ISSN=2296-634X

ABSTRACT=Abstract
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-MenSC therapy were evaluated in vivo in ARDS-induced (Escherichia coli lipopolysaccharide) C57/BL6 mice. After 24 h, the animals were treated with five doses ranging from 0.25×105 to 1.25×106 cells/animal. At 2 and 7 days after induction of ARDS, safety and efficacy were evaluated.
Results Clinical-grade cryo-MenSC injections improved lung mechanics and reduced alveolar collapse, tissue cellularity, and remodeling, 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 4×106 cell/Kg than with higher or lower doses.
Conclusions 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, favoring 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.