@article{5ba2d9f2d9494219986e46f2fcfc7cfd,
title = "Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial",
abstract = "Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS. A double-blind, phase 1/2a, randomized, controlled trial was performed. Randomization and stratification by ARDS severity was used to foster balance among groups. All subjects were analyzed under intention to treat design. Twenty-four subjects were randomized 1:1 to either UC-MSC treatment (n = 12) or the control group (n = 12). Subjects in the UC-MSC treatment group received two intravenous infusions (at day 0 and 3) of 100 ± 20 × 106 UC-MSCs; controls received two infusions of vehicle solution. Both groups received best standard of care. Primary endpoint was safety (adverse events [AEs]) within 6 hours; cardiac arrest or death within 24 hours postinfusion). Secondary endpoints included patient survival at 31 days after the first infusion and time to recovery. No difference was observed between groups in infusion-associated AEs. No serious adverse events (SAEs) were observed related to UC-MSC infusions. UC-MSC infusions in COVID-19 ARDS were found to be safe. Inflammatory cytokines were significantly decreased in UC-MSC-treated subjects at day 6. Treatment was associated with significantly improved patient survival (91% vs 42%, P =.015), SAE-free survival (P =.008), and time to recovery (P =.03). UC-MSC infusions are safe and could be beneficial in treating subjects with COVID-19 ARDS.",
keywords = "cell transplantation, cellular therapy, clinical trials, mesenchymal stem cells, respiratory tract, transplantation, umbilical cord",
author = "Giacomo Lanzoni and Elina Linetsky and Diego Correa and {Messinger Cayetano}, Shari and Alvarez, {Roger A.} and Dimitrios Kouroupis and {Alvarez Gil}, Ana and Raffaella Poggioli and Phillip Ruiz and Marttos, {Antonio C.} and Khemraj Hirani and Bell, {Crystal A.} and Halina Kusack and Lisa Rafkin and David Baidal and Andrew Pastewski and Kunal Gawri and Clarissa Le{\~n}ero and Mantero, {Alejandro M.A.} and Metalonis, {Sarah W.} and Xiaojing Wang and Luis Roque and Burlett Masters and Kenyon, {Norma S.} and Enrique Ginzburg and Xiumin Xu and Jianming Tan and Caplan, {Arnold I.} and Glassberg, {Marilyn K.} and Rodolfo Alejandro and Camillo Ricordi",
note = "Funding Information: The authors wish to thank the North America's Building Trades Unions (NABTU), The Cure Alliance, the Diabetes Research Institute Foundation (DRIF), the Barilla Group and Family, the Fondazione Silvio Tronchetti Provera, the Simkins Family Foundation, and Ugo Colombo for funding this clinical trial; Dr. Amit N Patel for the invaluable contributions to UC‐MSC manufacturing and infusion protocols over the years; Jadi Cell for providing the initial UC‐MSC master cell bank (cells provided at no cost by JadiCell ‐ US Patent # 9,803,176 B2) used in this trial, further expanded at the Diabetes Research Institute (DRI) cGMP Facility to generate the Investigational Product; Drs. George Burke and Ronald Goldberg for serving as Medical Monitor and DSMB Chair; the DRI‐Cell Transplant Center cGMP Staff; Joana R.N. Lemos for the help with data analysis; Melissa Willman for the help in experimental design; and the Clinical Translational Research Site at the Miami Clinical and Translational Science Institute (UL1TR000460) from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. The trial was supported by unrestricted donations from the North America's Building Trades Unions (NABTU), The Cure Alliance, the Diabetes Research Institute Foundation (DRIF), the Barilla Group and Family, the Fondazione Silvio Tronchetti Provera, the Simkins Family Foundation, and Ugo Colombo. This publication was supported by the Clinical Translational Research Site Grants Number UL1TR000460 and UL1TR002736 from the National Center for Advancing Translational Sciences (NCATS). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The funding sources had no roles in study design, patient recruitment, data collection, data analysis, data interpretation, or writing the report. None of the authors has been paid to write this article by a pharmaceutical company or other agency. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit this manuscript for publication. Funding Information: The authors wish to thank the North America's Building Trades Unions (NABTU), The Cure Alliance, the Diabetes Research Institute Foundation (DRIF), the Barilla Group and Family, the Fondazione Silvio Tronchetti Provera, the Simkins Family Foundation, and Ugo Colombo for funding this clinical trial; Dr. Amit N Patel for the invaluable contributions to UC-MSC manufacturing and infusion protocols over the years; Jadi Cell for providing the initial UC-MSC master cell bank (cells provided at no cost by JadiCell - US Patent # 9,803,176 B2) used in this trial, further expanded at the Diabetes Research Institute (DRI) cGMP Facility to generate the Investigational Product; Drs. George Burke and Ronald Goldberg for serving as Medical Monitor and DSMB Chair; the DRI-Cell Transplant Center cGMP Staff; Joana R.N. Lemos for the help with data analysis; Melissa Willman for the help in experimental design; and the Clinical Translational Research Site at the Miami Clinical and Translational Science Institute (UL1TR000460) from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. The trial was supported by unrestricted donations from the North America's Building Trades Unions (NABTU), The Cure Alliance, the Diabetes Research Institute Foundation (DRIF), the Barilla Group and Family, the Fondazione Silvio Tronchetti Provera, the Simkins Family Foundation, and Ugo Colombo. This publication was supported by the Clinical Translational Research Site Grants Number UL1TR000460 and UL1TR002736 from the National Center for Advancing Translational Sciences (NCATS). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The funding sources had no roles in study design, patient recruitment, data collection, data analysis, data interpretation, or writing the report. None of the authors has been paid to write this article by a pharmaceutical company or other agency. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit this manuscript for publication. Publisher Copyright: {\textcopyright} 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press",
year = "2021",
month = may,
doi = "10.1002/sctm.20-0472",
language = "English (US)",
volume = "10",
pages = "660--673",
journal = "Stem cells translational medicine",
issn = "2157-6564",
publisher = "AlphaMed Press",
number = "5",
}