PMID- 22047808
OWN - NLM
STAT- MEDLINE
DCOM- 20120424
LR  - 20211020
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 52
IP  - 1
DP  - 2012 Jan
TI  - Ischemia induces P-selectin-mediated selective progenitor cell engraftment in the 
      isolated-perfused heart.
PG  - 105-12
LID - 10.1016/j.yjmcc.2011.10.009 [doi]
AB  - Clinical trials infusing Bone Marrow Cells (BMCs) into injured hearts have 
      produced measureable improvements in cardiac performance, but were insufficient 
      to improve patient outcomes. Low engraftment rates are cited as probable 
      contributor to limited improvements. To understand the mechanisms that control 
      myocardial engraftment of BMCs following ischemia-reperfusion injury, in 
      isolated-perfused mouse hearts, stop-flow ischemia was followed by 
      variable-duration reperfusion (0-60 min) before addition of labeled syngenic BMCs 
      to the perfusate. After a buffer-only wash, the heart was disaggregated. Retained 
      BMCs (digest) and infused BMCs (aliquot) were compared by flow cytometry for 
      c-kit and CD45 expression to determine the proportion of cell subtypes engrafted 
      versus delivered (selectivity ratio). In these studies, a time-dependent 
      selective retention of c-kit(+) cells was apparent starting at 30 min of 
      reperfusion, at which time c-kit(+)/CD45(+) BMCs showed a selectivity ratio of 18 
      +/- 2 (versus 2 +/- 1 in sham-ischemic controls). To study the underlying mechanism 
      for this selective retention, neutralizing antibodies for P-selectin or 
      L-selectin were infused into the heart preparation and incubated with BMCs prior 
      to BMC infusion. Blocking P-selectin in ischemic hearts ablated selectivity for 
      c-kit(+)/CD45(+) BMCs at 30 min reperfusion (selectivity ratio of 3 +/- 1) while 
      selectivity persisted in the presence of L-selectin neutralization (selectivity 
      ratio of 17 +/- 2). To corroborate this finding, a parallel plate flow chamber was 
      used to study capture and rolling dynamics of purified c-kit(+) versus c-kit- 
      BMCs on various selectin molecules. C-kit(+) BMCs interacted weakly with 
      L-selectin substrates (0.03 +/- 0.01% adhered) but adhered strongly to P-selectin 
      (0.28+/-0.04% adhered). C-kit- BMCs showed intermediate binding regardless of 
      substrate (0.18 +/- 0.04% adhered on L-selectin versus 0.17 +/- 0.04% adhered on 
      P-selectin). Myocardial ischemia-reperfusion stress induces selective engraftment 
      of c-kit(+) bone marrow progenitor cells via P-selectin activation.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Elser, Jeremy Alan
AU  - Elser JA
AD  - Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Purcell, Brendan P
AU  - Purcell BP
FAU - Allana, Irshad A
AU  - Allana IA
FAU - Burdick, Jason A
AU  - Burdick JA
FAU - Margulies, Kenneth B
AU  - Margulies KB
LA  - eng
GR  - R01 HL089847/HL/NHLBI NIH HHS/United States
GR  - R01 HL089847-02/HL/NHLBI NIH HHS/United States
GR  - 1HL089847/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111025
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (P-Selectin)
RN  - 126880-86-2 (L-Selectin)
SB  - IM
MH  - Animals
MH  - Antibodies, Neutralizing/pharmacology
MH  - Bone Marrow Cells/*metabolism
MH  - *Bone Marrow Transplantation
MH  - Cell Adhesion
MH  - Cell Movement
MH  - Immunophenotyping
MH  - L-Selectin/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Ischemia/*metabolism
MH  - *Myocardial Reperfusion
MH  - P-Selectin/antagonists & inhibitors/*metabolism
MH  - Stem Cells/*metabolism
MH  - Transplantation, Autologous
PMC - PMC3246079
MID - NIHMS334972
EDAT- 2011/11/04 06:00
MHDA- 2012/04/25 06:00
PMCR- 2013/01/01
CRDT- 2011/11/04 06:00
PHST- 2010/09/11 00:00 [received]
PHST- 2011/09/28 00:00 [revised]
PHST- 2011/10/12 00:00 [accepted]
PHST- 2011/11/04 06:00 [entrez]
PHST- 2011/11/04 06:00 [pubmed]
PHST- 2012/04/25 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - S0022-2828(11)00436-6 [pii]
AID - 10.1016/j.yjmcc.2011.10.009 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2012 Jan;52(1):105-12. doi: 10.1016/j.yjmcc.2011.10.009. Epub 
      2011 Oct 25.