PMID- 23894446
OWN - NLM
STAT- MEDLINE
DCOM- 20140303
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - Sustained-release delivery of prostacyclin analogue enhances bone marrow-cell 
      recruitment and yields functional benefits for acute myocardial infarction in 
      mice.
PG  - e69302
LID - 10.1371/journal.pone.0069302 [doi]
LID - e69302
AB  - BACKGROUND: A prostacyclin analogue, ONO-1301, is reported to upregulate 
      beneficial proteins, including stromal cell derived factor-1 (SDF-1). We 
      hypothesized that the sustained-release delivery of ONO-1301 would enhance SDF-1 
      expression in the acute myocardial infarction (MI) heart and induce bone marrow 
      cells (BMCs) to home to the myocardium, leading to improved cardiac function in 
      mice. METHODS AND RESULTS: ONO-1301 significantly upregulated SDF-1 secretion by 
      fibroblasts. BMC migration was greater to ONO-1301-stimulated than unstimulated 
      conditioned medium. This increase was diminished by treating the BMCs with a 
      CXCR4-neutralizing antibody or CXCR4 antagonist (AMD3100). Atelocollagen sheets 
      containing a sustained-release form of ONO-1301 (n = 33) or ONO-1301-free vehicle 
      (n = 48) were implanted on the left ventricular (LV) anterior wall immediately 
      after permanent left-anterior descending artery occlusion in C57BL6/N mice (male, 
      8-weeks-old). The SDF-1 expression in the infarct border zone was significantly 
      elevated for 1 month in the ONO-1301-treated group. BMC accumulation in the 
      infarcted hearts, detected by in vivo imaging after intravenous injection of 
      labeled BMCs, was enhanced in the ONO-1301-treated hearts. This increase was 
      inhibited by AMD3100. The accumulated BMCs differentiated into capillary 
      structures. The survival rates and cardiac function were significantly improved 
      in the ONO-1301-treated group (fractional area change 23+/-1%; n = 22) compared to 
      the vehicle group (19+/-1%; n = 20; P = 0.004). LV anterior wall thinning, 
      expansion of infarction, and fibrosis were lower in the ONO-1301-treated group. 
      CONCLUSIONS: Sustained-release delivery of ONO-1301 promoted BMC recruitment to 
      the acute MI heart via SDF-1/CXCR4 signaling and restored cardiac performance, 
      suggesting a novel mechanism for ONO-1301-mediated acute-MI heart repair.
FAU - Imanishi, Yukiko
AU  - Imanishi Y
AD  - Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka 
      University, Osaka, Japan.
FAU - Miyagawa, Shigeru
AU  - Miyagawa S
FAU - Fukushima, Satsuki
AU  - Fukushima S
FAU - Ishimaru, Kazuhiko
AU  - Ishimaru K
FAU - Sougawa, Nagako
AU  - Sougawa N
FAU - Saito, Atsuhiro
AU  - Saito A
FAU - Sakai, Yoshiki
AU  - Sakai Y
FAU - Sawa, Yoshiki
AU  - Sawa Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130719
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, CXCR4)
RN  - 176391-41-6 (ONO 1301)
RN  - DCR9Z582X0 (Epoprostenol)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology/*drug effects/*metabolism
MH  - Bone Marrow Transplantation
MH  - Cell Differentiation/drug effects
MH  - Cell Movement/drug effects
MH  - Chemokine CXCL12/metabolism
MH  - Disease Models, Animal
MH  - Epoprostenol/*administration & dosage/analogs & derivatives
MH  - Humans
MH  - Male
MH  - Mice
MH  - Myocardial Infarction/*metabolism/mortality/physiopathology/therapy
MH  - Myocardium/*metabolism/pathology
MH  - Pyridines/*administration & dosage
MH  - Receptors, CXCR4/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
MH  - Ventricular Remodeling
PMC - PMC3716598
COIS- Competing Interests: The authors have read the journal's policy and have the 
      following conflicts: Y. Sakai was an employee of Ono Pharmaceutical Co. Ltd., and 
      a holder of the patent for ONO-1301 encapsulated in PLGA microspheres (patent 
      numbers WO 2004/032965 and WO 2008/047863). There are no other patents, products 
      in development, or modified products to declare. The other authors have declared 
      that no competing interests exist. This does not alter the authors' adherence to 
      all PLOS ONE policies on sharing data and materials.
EDAT- 2013/07/31 06:00
MHDA- 2014/03/04 06:00
PMCR- 2013/07/19
CRDT- 2013/07/30 06:00
PHST- 2013/02/08 00:00 [received]
PHST- 2013/06/06 00:00 [accepted]
PHST- 2013/07/30 06:00 [entrez]
PHST- 2013/07/31 06:00 [pubmed]
PHST- 2014/03/04 06:00 [medline]
PHST- 2013/07/19 00:00 [pmc-release]
AID - PONE-D-13-05848 [pii]
AID - 10.1371/journal.pone.0069302 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 19;8(7):e69302. doi: 10.1371/journal.pone.0069302. Print 2013.