PMID- 27806113
OWN - NLM
STAT- MEDLINE
DCOM- 20170622
LR  - 20200306
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 11
DP  - 2016
TI  - Inhibiting Extracellular Vesicle Release from Human Cardiosphere Derived Cells 
      with Lentiviral Knockdown of nSMase2 Differentially Effects Proliferation and 
      Apoptosis in Cardiomyocytes, Fibroblasts and Endothelial Cells In Vitro.
PG  - e0165926
LID - 10.1371/journal.pone.0165926 [doi]
LID - e0165926
AB  - Numerous studies have shown a beneficial effect of cardiosphere-derived cell 
      (CDC) therapy on regeneration of injured myocardium. Paracrine signaling by CDC 
      secreted exosomes may contribute to improved cardiac function. However, it has 
      not yet been demonstrated by a genetic approach that exosome release contributes 
      to the therapeutic effect of transplanted CDCs. By employing a lentiviral 
      knockdown (KD) strategy against neutral spingomyelinase 2 (nSMase2), a crucial 
      gene in exosome secretion, we have defined the role of physiologically secreted 
      human CDC-derived exosomes on cardiac fibroblast, endothelial cell and primary 
      cardiomyocyte proliferation, cell death, migration and angiogenesis using a 
      series of in vitro coculture assays. We found that secretion of hCDC-derived 
      exosomes was effectively inhibited by nSMase2 lentiviral KD and shRNAi expression 
      was stable and constitutive. hCDC exosome release contributed to the angiogenic 
      and pro-migratory effects of hCDCs on HUVECs, decreased proliferation of 
      fibroblasts, and decreased apoptosis of cardiomyocytes. These in vitro reactions 
      support a role for exosome secretion as a paracrine mechanism of stem 
      cell-mediated cardiac repair in vivo. Importantly, we have established a novel 
      tool to test constitutive inhibition of exosome secretion in stem cell 
      populations in animal models of cardiac disease.
FAU - Lang, Jennifer K
AU  - Lang JK
AUID- ORCID: 0000-0002-6221-8625
AD  - Department of Medicine, Division of Cardiology, Jacobs School of Medicine and 
      Biomedical Sciences, Buffalo, N.Y, 14203, United States of America.
FAU - Young, Rebeccah F
AU  - Young RF
AD  - Department of Medicine, Division of Cardiology, Jacobs School of Medicine and 
      Biomedical Sciences, Buffalo, N.Y, 14203, United States of America.
FAU - Ashraf, Hashmat
AU  - Ashraf H
AD  - Department of Cardiothoracic Surgery, Kaleida Health, Buffalo, N.Y, 14203, United 
      States of America.
FAU - Canty, John M Jr
AU  - Canty JM Jr
AD  - Department of Medicine, Division of Cardiology, Jacobs School of Medicine and 
      Biomedical Sciences, Buffalo, N.Y, 14203, United States of America.
AD  - VA WNY Healthcare System, Buffalo, N.Y., 14215, United States of America.
LA  - eng
GR  - R01 HL055324/HL/NHLBI NIH HHS/United States
GR  - R01 HL061610/HL/NHLBI NIH HHS/United States
GR  - UL1 TR001412/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20161102
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 3.1.4.12 (SMPD3 protein, human)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
SB  - IM
MH  - Apoptosis
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Endothelial Cells/*cytology
MH  - Extracellular Vesicles/*metabolism
MH  - Fibroblasts/*cytology
MH  - Gene Knockdown Techniques/*methods
MH  - Humans
MH  - In Vitro Techniques
MH  - Lentivirus/genetics
MH  - Myocytes, Cardiac/*cytology
MH  - Paracrine Communication
MH  - Sphingomyelin Phosphodiesterase/*genetics
PMC - PMC5091915
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/11/03 06:00
MHDA- 2017/06/24 06:00
PMCR- 2016/11/02
CRDT- 2016/11/03 06:00
PHST- 2016/08/18 00:00 [received]
PHST- 2016/10/19 00:00 [accepted]
PHST- 2016/11/03 06:00 [pubmed]
PHST- 2017/06/24 06:00 [medline]
PHST- 2016/11/03 06:00 [entrez]
PHST- 2016/11/02 00:00 [pmc-release]
AID - PONE-D-16-33142 [pii]
AID - 10.1371/journal.pone.0165926 [doi]
PST - epublish
SO  - PLoS One. 2016 Nov 2;11(11):e0165926. doi: 10.1371/journal.pone.0165926. 
      eCollection 2016.