PMID- 33400390
OWN - NLM
STAT- MEDLINE
DCOM- 20210426
LR  - 20240331
IS  - 2157-6580 (Electronic)
IS  - 2157-6564 (Print)
IS  - 2157-6564 (Linking)
VI  - 10
IP  - 5
DP  - 2021 May
TI  - Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress 
      syndrome: A double-blind, phase 1/2a, randomized controlled trial.
PG  - 660-673
LID - 10.1002/sctm.20-0472 [doi]
AB  - 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 x 10(6) 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.
CI  - (c) 2021 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley 
      Periodicals LLC on behalf of AlphaMed Press.
FAU - Lanzoni, Giacomo
AU  - Lanzoni G
AUID- ORCID: 0000-0003-3996-4803
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
AD  - Department of Biochemistry and Molecular Biology, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Linetsky, Elina
AU  - Linetsky E
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
AD  - Department of Surgery, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
FAU - Correa, Diego
AU  - Correa D
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
AD  - Department of Orthopedics, UHealth Sports Medicine Institute, University of Miami 
      Miller School of Medicine, Miami, Florida, USA.
FAU - Messinger Cayetano, Shari
AU  - Messinger Cayetano S
AD  - Division of Biostatistics, Department of Public Health Sciences, University of 
      Miami Miller School of Medicine, Miami, Florida, USA.
FAU - Alvarez, Roger A
AU  - Alvarez RA
AD  - Department of Medicine, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
AD  - University of Miami Health System, Miami, Florida, USA.
FAU - Kouroupis, Dimitrios
AU  - Kouroupis D
AUID- ORCID: 0000-0002-3892-9013
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Alvarez Gil, Ana
AU  - Alvarez Gil A
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Poggioli, Raffaella
AU  - Poggioli R
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Ruiz, Phillip
AU  - Ruiz P
AD  - Department of Surgery, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
FAU - Marttos, Antonio C
AU  - Marttos AC
AD  - Department of Medicine, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
AD  - University of Miami Health System, Miami, Florida, USA.
AD  - Jackson Health System, Miami, Florida, USA.
FAU - Hirani, Khemraj
AU  - Hirani K
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
AD  - Department of Medicine, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
FAU - Bell, Crystal A
AU  - Bell CA
AD  - Department of Medicine, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
FAU - Kusack, Halina
AU  - Kusack H
AD  - Department of Medicine, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
FAU - Rafkin, Lisa
AU  - Rafkin L
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Baidal, David
AU  - Baidal D
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
AD  - Department of Medicine, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
AD  - University of Miami Health System, Miami, Florida, USA.
FAU - Pastewski, Andrew
AU  - Pastewski A
AD  - Jackson Health System, Miami, Florida, USA.
FAU - Gawri, Kunal
AU  - Gawri K
AD  - Department of Medicine, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
AD  - University of Miami Health System, Miami, Florida, USA.
FAU - Lenero, Clarissa
AU  - Lenero C
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Mantero, Alejandro M A
AU  - Mantero AMA
AD  - Division of Biostatistics, Department of Public Health Sciences, University of 
      Miami Miller School of Medicine, Miami, Florida, USA.
FAU - Metalonis, Sarah W
AU  - Metalonis SW
AD  - Division of Biostatistics, Department of Public Health Sciences, University of 
      Miami Miller School of Medicine, Miami, Florida, USA.
FAU - Wang, Xiaojing
AU  - Wang X
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Roque, Luis
AU  - Roque L
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Masters, Burlett
AU  - Masters B
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Kenyon, Norma S
AU  - Kenyon NS
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Ginzburg, Enrique
AU  - Ginzburg E
AD  - Department of Surgery, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
AD  - University of Miami Health System, Miami, Florida, USA.
AD  - Jackson Health System, Miami, Florida, USA.
FAU - Xu, Xiumin
AU  - Xu X
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
FAU - Tan, Jianming
AU  - Tan J
AD  - The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 
      People's Republic of China.
FAU - Caplan, Arnold I
AU  - Caplan AI
AD  - Skeletal Research Center, Case Western Reserve University, Cleveland, Ohio, USA.
FAU - Glassberg, Marilyn K
AU  - Glassberg MK
AD  - University of Arizona College of Medicine, Tucson, Arizona, USA.
FAU - Alejandro, Rodolfo
AU  - Alejandro R
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
AD  - Department of Medicine, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
AD  - University of Miami Health System, Miami, Florida, USA.
FAU - Ricordi, Camillo
AU  - Ricordi C
AD  - Diabetes Research Institute, Cell Transplant Center, University of Miami Miller 
      School of Medicine, Miami, Florida, USA.
AD  - Department of Surgery, University of Miami Miller School of Medicine, Miami, 
      Florida, USA.
LA  - eng
GR  - The Cure Alliance/
GR  - UL1 TR002736/TR/NCATS NIH HHS/United States
GR  - UL1TR000460/TR/NCATS NIH HHS/United States
GR  - Simkins Family Foundation/
GR  - Diabetes Research Institute Foundation (DRIF)/
GR  - Ugo Colombo/
GR  - North America's Building Trades Unions (NABTU)/
GR  - Barilla Group and Family/
GR  - UL1TR002736/TR/NCATS NIH HHS/United States
GR  - Fondazione Silvio Tronchetti Provera/
GR  - UL1 TR000460/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210105
PL  - England
TA  - Stem Cells Transl Med
JT  - Stem cells translational medicine
JID - 101578022
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
SB  - IM
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - COVID-19/*therapy
MH  - Cytokines/blood
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/adverse effects/*methods
MH  - Mesenchymal Stem Cells
MH  - Middle Aged
MH  - SARS-CoV-2/drug effects
MH  - Severity of Illness Index
MH  - Treatment Outcome
MH  - Umbilical Cord/cytology
PMC - PMC8046040
OTO - NOTNLM
OT  - cell transplantation
OT  - cellular therapy
OT  - clinical trials
OT  - mesenchymal stem cells
OT  - respiratory tract
OT  - transplantation
OT  - umbilical cord
COIS- The authors declared no potential conflicts of interest.
EDAT- 2021/01/06 06:00
MHDA- 2021/04/27 06:00
PMCR- 2021/01/05
CRDT- 2021/01/05 12:20
PHST- 2020/11/22 00:00 [revised]
PHST- 2020/10/23 00:00 [received]
PHST- 2020/12/06 00:00 [accepted]
PHST- 2021/01/06 06:00 [pubmed]
PHST- 2021/04/27 06:00 [medline]
PHST- 2021/01/05 12:20 [entrez]
PHST- 2021/01/05 00:00 [pmc-release]
AID - SCT312883 [pii]
AID - 10.1002/sctm.20-0472 [doi]
PST - ppublish
SO  - Stem Cells Transl Med. 2021 May;10(5):660-673. doi: 10.1002/sctm.20-0472. Epub 
      2021 Jan 5.