PMID- 16510464
OWN - NLM
STAT- MEDLINE
DCOM- 20060629
LR  - 20151119
IS  - 0195-668X (Print)
IS  - 0195-668X (Linking)
VI  - 27
IP  - 9
DP  - 2006 May
TI  - A quantitative, randomized study evaluating three methods of mesenchymal stem 
      cell delivery following myocardial infarction.
PG  - 1114-22
AB  - AIMS: Mesenchymal stem cells (MSCs), rare bone marrow-derived stem cell 
      precursors of non-haematopoietic tissues, have shown promise in potentially 
      repairing infarcted myocardium. These and similar cell types are being tested 
      clinically, but understanding of delivery and subsequent biodistribution is 
      lacking. This study was designed to quantitatively compare MSC engraftment rates 
      after intravenous (IV), intracoronary (IC), or endocardial (EC) delivery in a 
      porcine myocardial infarction (MI) model. METHODS AND RESULTS: Allogeneic, male 
      MSCs were cultured from porcine bone marrow aspirates. Iridium nanoparticles were 
      added during culturing and internalized by the MSCs. An MI was induced in female 
      swine (27-40 kg in size) by prolonged balloon occlusion of the mid-left anterior 
      descending artery. Animals (n = 6 per group) were randomized to one of three 
      delivery methods. Cellular engraftment was determined 14+/-3 days post-delivery 
      by measuring ex-vivo the iridium nanoparticle concentration in the infarct. 
      Confirmation of cellular engraftment utilized both DiI and fluorescence in situ 
      hybridization (FISH) labelling techniques. During MSC infusion, no adverse events 
      were noted. However, following IC infusion, half of the pigs exhibited decreased 
      blood flow distal to the infusion site. At 14 days, the mean number of engrafted 
      cells within the infarct zone was significantly greater (P< or =0.01) following 
      IC infusion than either EC injection or IV infusion and EC engraftment was 
      greater than IV engraftment (P< or =0.01). There was less systemic delivery to 
      the lungs following [EC vs. IV (P = 0.02), EC vs. IC (P = 0.06)]. Both DiI and 
      FISH labelling demonstrated the presence of engrafted male MSCs within the female 
      infarcted tissue. CONCLUSION: IC and EC injection of MSCs post-MI resulted in 
      increased engraftment within infarcted tissue when compared with IV infusion, and 
      IC was more efficient than EC. However, IC delivery was also associated with a 
      higher incidence of decreased coronary blood flow. EC delivery into acutely 
      infarcted myocardial tissue was safe and well tolerated and was associated with 
      decreased remote organ engraftment with compared with IC and IV deliveries.
FAU - Freyman, Toby
AU  - Freyman T
AD  - Boston Scientific Corporation, Natick, MA, USA.
FAU - Polin, Glenn
AU  - Polin G
FAU - Osman, Hashim
AU  - Osman H
FAU - Crary, Jody
AU  - Crary J
FAU - Lu, MinMin
AU  - Lu M
FAU - Cheng, Lan
AU  - Cheng L
FAU - Palasis, Maria
AU  - Palasis M
FAU - Wilensky, Robert L
AU  - Wilensky RL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060301
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Iridium Radioisotopes)
SB  - IM
MH  - Animals
MH  - Female
MH  - Graft Survival
MH  - Infusions, Intralesional
MH  - Infusions, Intravenous
MH  - Injections
MH  - Iridium Radioisotopes
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/*methods/standards
MH  - Myocardial Infarction/pathology/*therapy
MH  - Random Allocation
MH  - Swine
EDAT- 2006/03/03 09:00
MHDA- 2006/06/30 09:00
CRDT- 2006/03/03 09:00
PHST- 2006/03/03 09:00 [pubmed]
PHST- 2006/06/30 09:00 [medline]
PHST- 2006/03/03 09:00 [entrez]
AID - ehi818 [pii]
AID - 10.1093/eurheartj/ehi818 [doi]
PST - ppublish
SO  - Eur Heart J. 2006 May;27(9):1114-22. doi: 10.1093/eurheartj/ehi818. Epub 2006 Mar 
      1.