PMID- 22504485
OWN - NLM
STAT- MEDLINE
DCOM- 20120727
LR  - 20221109
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 18
IP  - 5
DP  - 2012 Apr 15
TI  - Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary 
      alveoli protects against acute lung injury.
PG  - 759-65
LID - 10.1038/nm.2736 [doi]
AB  - Bone marrow-derived stromal cells (BMSCs) protect against acute lung injury 
      (ALI). To determine the role of BMSC mitochondria in this protection, we 
      airway-instilled mice first with lipopolysaccharide (LPS) and then with either 
      mouse BMSCs (mBMSCs) or human BMSCs (hBMSCs). Live optical studies revealed that 
      the mBMSCs formed connexin 43 (Cx43)-containing gap junctional channels (GJCs) 
      with the alveolar epithelia in these mice, releasing mitochondria-containing 
      microvesicles that the epithelia engulfed. The presence of BMSC-derived 
      mitochondria in the epithelia was evident optically, as well as by the presence 
      of human mitochondrial DNA in mouse lungs instilled with hBMSCs. The 
      mitochondrial transfer resulted in increased alveolar ATP concentrations. 
      LPS-induced ALI, as indicated by alveolar leukocytosis and protein leak, 
      inhibition of surfactant secretion and high mortality, was markedly abrogated by 
      the instillation of wild-type mBMSCs but not of mutant, GJC-incompetent mBMSCs or 
      mBMSCs with dysfunctional mitochondria. This is the first evidence, to our 
      knowledge, that BMSCs protect against ALI by restituting alveolar bioenergetics 
      through Cx43-dependent alveolar attachment and mitochondrial transfer.
FAU - Islam, Mohammad Naimul
AU  - Islam MN
AD  - Lung Biology Laboratory, Department of Medicine, Division of Pulmonary, Allergy 
      and Critical Care Medicine, College of Physicians and Surgeons of Columbia 
      University, New York, New York, USA.
FAU - Das, Shonit R
AU  - Das SR
FAU - Emin, Memet T
AU  - Emin MT
FAU - Wei, Michelle
AU  - Wei M
FAU - Sun, Li
AU  - Sun L
FAU - Westphalen, Kristin
AU  - Westphalen K
FAU - Rowlands, David J
AU  - Rowlands DJ
FAU - Quadri, Sadiqa K
AU  - Quadri SK
FAU - Bhattacharya, Sunita
AU  - Bhattacharya S
FAU - Bhattacharya, Jahar
AU  - Bhattacharya J
LA  - eng
GR  - R01 HL057556/HL/NHLBI NIH HHS/United States
GR  - R37 HL036024/HL/NHLBI NIH HHS/United States
GR  - R01 HL036024/HL/NHLBI NIH HHS/United States
GR  - R01 HL064896/HL/NHLBI NIH HHS/United States
GR  - HL64896/HL/NHLBI NIH HHS/United States
GR  - HL36024/HL/NHLBI NIH HHS/United States
GR  - HL57556/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120415
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Connexin 43)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
CIN - Nat Med. 2012 May;18(5):653-4. PMID: 22561816
MH  - Acute Lung Injury/*prevention & control
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Bone Marrow Cells/*physiology
MH  - Connexin 43/physiology
MH  - Energy Metabolism
MH  - Gap Junctions/physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*physiology
MH  - Pulmonary Alveoli/*metabolism
MH  - Stromal Cells/physiology
PMC - PMC3727429
MID - NIHMS493265
COIS- Conflicts of interest: None
EDAT- 2012/04/17 06:00
MHDA- 2012/07/28 06:00
PMCR- 2013/07/30
CRDT- 2012/04/17 06:00
PHST- 2012/01/18 00:00 [received]
PHST- 2012/03/16 00:00 [accepted]
PHST- 2012/04/17 06:00 [entrez]
PHST- 2012/04/17 06:00 [pubmed]
PHST- 2012/07/28 06:00 [medline]
PHST- 2013/07/30 00:00 [pmc-release]
AID - nm.2736 [pii]
AID - 10.1038/nm.2736 [doi]
PST - epublish
SO  - Nat Med. 2012 Apr 15;18(5):759-65. doi: 10.1038/nm.2736.