PMID- 28960096
OWN - NLM
STAT- MEDLINE
DCOM- 20190410
LR  - 20190410
IS  - 1535-4970 (Electronic)
IS  - 1073-449X (Linking)
VI  - 197
IP  - 3
DP  - 2018 Feb 1
TI  - Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial.
PG  - 337-347
LID - 10.1164/rccm.201705-1006OC [doi]
AB  - RATIONALE: In septic animal models mesenchymal stem (stromal) cells (MSCs) 
      modulate inflammation, enhance tissue repair and pathogen clearance, and reduce 
      death. OBJECTIVES: To conduct a phase I dose escalation trial of MSCs in septic 
      shock with the primary objective of examining the safety and tolerability of 
      MSCs. METHODS: We enrolled nine participants within 24 hours of admission to the 
      ICU. A control cohort of 21 participants was enrolled before starting the MSC 
      interventional cohort to characterize expected adverse events (AEs) and to serve 
      as a comparator for the intervention cohort. Three separate MSC dose cohorts, 
      with three participants per cohort, received a single intravenous dose of 0.3, 
      1.0, and 3.0 x 10(6) cells/kg. A prespecified safety plan monitored participants 
      for the occurrence of AEs; cytokines were collected at prespecified time points. 
      MEASUREMENTS AND MAIN RESULTS: Ages of participants in the interventional versus 
      observational cohorts were median of 71 (range, 38-91) and 61 (range, 23-95). 
      Acute Physiology and Chronic Health Evaluation scores were median of 25 (range, 
      11-28) and 26 (range, 17-32). MSC doses ranged from 19 to 250 million cells. 
      There were no prespecified MSC infusion-associated or serious unexpected AEs, nor 
      any safety or efficacy signals for the expected AEs or the measured cytokines 
      between the interventional and observational cohorts. CONCLUSIONS: The infusion 
      of freshly cultured allogenic bone marrow-derived MSCs, up to a dose of 3 million 
      cells/kg (250 million cells), into participants with septic shock seems safe. 
      Clinical trial registered with www.clinicaltrials.gov (NCT02421484).
FAU - McIntyre, Lauralyn A
AU  - McIntyre LA
AD  - 1 Division of Critical Care, Department of Medicine.
AD  - 3 Department of Epidemiology and Community Medicine, and.
AD  - 2 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
FAU - Stewart, Duncan J
AU  - Stewart DJ
AD  - 4 Department of Cell and Molecular Medicine, University of Ottawa, Ottawa, 
      Ontario, Canada.
AD  - 2 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
FAU - Mei, Shirley H J
AU  - Mei SHJ
AD  - 2 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
AD  - 5 Department of Regenerative Medicine, Ottawa Hospital Research Institute, 
      Ottawa, Ontario, Canada.
FAU - Courtman, David
AU  - Courtman D
AD  - 2 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
AD  - 5 Department of Regenerative Medicine, Ottawa Hospital Research Institute, 
      Ottawa, Ontario, Canada.
FAU - Watpool, Irene
AU  - Watpool I
AD  - 2 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
FAU - Granton, John
AU  - Granton J
AD  - 6 Department of Medicine and.
FAU - Marshall, John
AU  - Marshall J
AD  - 7 Department of Surgery and Critical Care Medicine, Keenan Research Centre of the 
      Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Dos Santos, Claudia
AU  - Dos Santos C
AD  - 7 Department of Surgery and Critical Care Medicine, Keenan Research Centre of the 
      Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 
      Toronto, Ontario, Canada.
FAU - Walley, Keith R
AU  - Walley KR
AD  - 8 Centre for Heart Lung Innovation, University of British Columbia, Vancouver, 
      British Columbia, Canada; and.
FAU - Winston, Brent W
AU  - Winston BW
AD  - 9 Department of Critical Care Medicine, Biochemistry and Molecular Biology, 
      Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
FAU - Schlosser, Kenny
AU  - Schlosser K
AD  - 2 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
AD  - 5 Department of Regenerative Medicine, Ottawa Hospital Research Institute, 
      Ottawa, Ontario, Canada.
FAU - Fergusson, Dean A
AU  - Fergusson DA
AD  - 3 Department of Epidemiology and Community Medicine, and.
AD  - 2 Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
CN  - Canadian Critical Care Trials Group
CN  - Canadian Critical Care Translational Biology Group
LA  - eng
SI  - ClinicalTrials.gov/NCT02421484
GR  - CIHR/Canada
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
SB  - IM
CIN - Am J Respir Crit Care Med. 2018 Feb 1;197(3):280-281. PMID: 29072926
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Allografts
MH  - Confidence Intervals
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Infusions, Intravenous
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Middle Aged
MH  - Risk Assessment
MH  - Sex Factors
MH  - Shock, Septic/diagnosis/mortality/*therapy
MH  - Survival Rate
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - allogeneic
OT  - bone marrow
OT  - mesenchymal stem cells
OT  - phase I clinical trial
OT  - septic shock
EDAT- 2017/09/30 06:00
MHDA- 2019/04/11 06:00
CRDT- 2017/09/30 06:00
PHST- 2017/09/30 06:00 [pubmed]
PHST- 2019/04/11 06:00 [medline]
PHST- 2017/09/30 06:00 [entrez]
AID - 10.1164/rccm.201705-1006OC [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 2018 Feb 1;197(3):337-347. doi: 
      10.1164/rccm.201705-1006OC.