PMID- 34164564 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210626 IS - 2329-7042 (Print) IS - 2329-7042 (Electronic) VI - 8 DP - 2020 TI - Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients with Acute Respiratory Distress Syndrome (ARDS). LID - e2839 [pii] LID - 10.32113/cellr4_20204_2839 [doi] AB - The coronavirus SARS-CoV-2 is cause of a global pandemic of a pneumonia-like disease termed Coronavirus Disease 2019 (COVID-19). COVID-19 presents a high mortality rate, estimated at 3.4%. More than 1 out of 4 hospitalized COVID-19 patients require admission to an Intensive Care Unit (ICU) for respiratory support, and a large proportion of these ICU-COVID-19 patients, between 17% and 46%, have died. In these patients COVID-19 infection causes an inflammatory response in the lungs that can progress to inflammation with cytokine storm, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), thromboembolic events, disseminated intravascular coagulation, organ failure, and death. Mesenchymal Stem Cells (MSCs) are potent immunomodulatory cells that recognize sites of injury, limit effector T cell reactions, and positively modulate regulatory cell populations. MSCs also stimulate local tissue regeneration via paracrine effects inducing angiogenic, anti-fibrotic and remodeling responses. MSCs can be derived in large number from the Umbilical Cord (UC). UC-MSCs, utilized in the allogeneic setting, have demonstrated safety and efficacy in clinical trials for a number of disease conditions including inflammatory and immune-based diseases. UC-MSCs have been shown to inhibit inflammation and fibrosis in the lungs and have been utilized to treat patients with severe COVID-19 in pilot, uncontrolled clinical trials, that reported promising results. UC-MSCs processed at our facility have been authorized by the FDA for clinical trials in patients with an Alzheimer's Disease, and in patients with Type 1 Diabetes (T1D). We hypothesize that UC-MSC will also exert beneficial therapeutic effects in COVID-19 patients with cytokine storm and ARDS. We propose an early phase controlled, randomized clinical trial in COVID-19 patients with ALI/ARDS. Subjects in the treatment group will be treated with two doses of UC-MSC (l00 x 10(6) cells). The first dose will be infused within 24 hours following study enrollment. A second dose will be administered 72 +/- 6 hours after the first infusion. Subject in the control group will receive infusion of vehicle (DPBS supplemented with 1% HSA and 70 U/kg unfractionated Heparin, delivered IV) following the same timeline. Subjects will be evaluated daily during the first 6 days, then at 14, 28, 60, and 90 days following enrollment (see Schedule of Assessment for time window details). Safety will be determined by adverse events (AEs) and serious adverse events (SAEs) during the follow-up period. Efficacy will be defined by clinical outcomes, as well as a variety of pulmonary, biochemical and immunological tests. Success of the current study will provide a framework for larger controlled, randomized clinical trials and a means of accelerating a possible solution for this urgent but unmet medical need. The proposed early phase clinical trial will be performed at the University of Miami (UM), in the facilities of the Diabetes Research Institute (DRI), UHealth Intensive Care Unit (ICU) and the Clinical Translational Research Site (CTRS) at the University of Miami Miller School of Medicine and at the Jackson Memorial Hospital (JMH). FAU - Lanzoni, G AU - Lanzoni G AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Linetsky, E AU - Linetsky E AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Correa, D AU - Correa D AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department of Orthopedics, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Alvarez, R A AU - Alvarez RA AD - University of Miami Health System and Jackson Health System, Miami, FL, USA. AD - Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Marttos, A AU - Marttos A AD - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. AD - University of Miami Health System and Jackson Health System, Miami, FL, USA. FAU - Hirani, K AU - Hirani K AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Cayetano, S Messinger AU - Cayetano SM AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Castro, J G AU - Castro JG AD - University of Miami Health System and Jackson Health System, Miami, FL, USA. AD - Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Paidas, M J AU - Paidas MJ AD - University of Miami Health System and Jackson Health System, Miami, FL, USA. AD - Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Efantis Potter, J AU - Efantis Potter J AD - Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Xu, X AU - Xu X AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Glassberg, M AU - Glassberg M AD - Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ, USA. FAU - Tan, J AU - Tan J AD - Organ Transplant Institute, Fuzhou General Hospital, Xiamen University, Fuzhou, China. FAU - Patel, A N AU - Patel AN AD - Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA. AD - HCA Research Institute, Nashville, TN, USA. FAU - Goldstein, B AU - Goldstein B AD - Department of Head and Neck Surgery and Communication Sciences, Duke University, Durham, NC, USA. FAU - Kenyon, N S AU - Kenyon NS AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Baidal, D AU - Baidal D AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Alejandro, R AU - Alejandro R AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Vianna, R AU - Vianna R AD - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. AD - University of Miami Health System and Jackson Health System, Miami, FL, USA. AD - Miami Transplant Institute, Jackson Health System, Miami, FL, USA. FAU - Ruiz, P AU - Ruiz P AD - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. AD - University of Miami Health System and Jackson Health System, Miami, FL, USA. AD - Miami Transplant Institute, Jackson Health System, Miami, FL, USA. FAU - Caplan, A I AU - Caplan AI AD - Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ, USA. FAU - Ricordi, C AU - Ricordi C AD - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller School of Medicine, Miami, FL, USA. AD - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. AD - University of Miami Health System and Jackson Health System, Miami, FL, USA. LA - eng GR - U01 DK070460/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20200428 PL - United States TA - CellR4 Repair Replace Regen Reprogram JT - CellR4-- repair, replacement, regeneration, & reprogramming JID - 101621391 PMC - PMC8218794 MID - NIHMS1589222 OTO - NOTNLM OT - Acute Respiratory Distress Syndrome (ARDS) OT - Coronavirus Disease 2019 (COVID-19) OT - Umbilical cord-derived mesenchymal stem cells (UC-MSCs) COIS- Conflict of Interest All authors declare that there are no conflicts of interest regarding the publication of this manuscript. EDAT- 2020/01/01 00:00 MHDA- 2020/01/01 00:01 PMCR- 2021/06/22 CRDT- 2021/06/24 06:40 PHST- 2021/06/24 06:40 [entrez] PHST- 2020/01/01 00:00 [pubmed] PHST- 2020/01/01 00:01 [medline] PHST- 2021/06/22 00:00 [pmc-release] AID - e2839 [pii] AID - 10.32113/cellr4_20204_2839 [doi] PST - ppublish SO - CellR4 Repair Replace Regen Reprogram. 2020;8:e2839. doi: 10.32113/cellr4_20204_2839. Epub 2020 Apr 28.