Safety of intramyocardial injection of autologous bone marrow cells to treat myocardial ischemia in pigs.
OBJECTIVE
The purpose of this study is to determine the potential adverse consequences of intracardiac injections of bone marrow mononuclear cells (BMCs) to facilitate the revascularization of ischemic myocardium.


BACKGROUND
Bone marrow mononuclear cells are used to treat heart failure, though there are few studies that evaluated the safety of BMC transplantation for chronic myocardial ischemia.


METHODS
The pigs received coronary ameroid constrictors to induce chronic myocardial ischemia and left ventricular dysfunction. At 4 weeks, autologous BMCs were injected intramyocardially by Boston Scientific Stiletto catheter with low-dose (10(7) cells) or high-dose BMC (10(8)). Control animals received saline. Blood samples were collected for hematological and chemical indices, including cardiac enzyme levels at regular time intervals postinfarction. At 7 weeks, animals underwent electrophysiological study to evaluate the arrhythmic potential of transplanted BMC, followed by necropsy and histopathology.


RESULTS
No mortalities were associated with intramyocardial delivery of BMC or saline. At Day 0, the total creatine phosphokinase (CPK) was in the normal range in all groups. All groups had significant elevations in CPK after ameroid placement, with no significant differences between groups. At 7 weeks, CPK in all groups had returned to pretreatment levels. Electrophysiological assessment revealed that one control animal had an inducible arrhythmia. No arrhythmias were induced in low- or high-dose BMC-treated pigs. There were no histopathological changes associated with BMC injection.


CONCLUSIONS
This study showed, in a clinically relevant large-animal model, that catheter-based intramyocardial injection of autologous BMC into ischemic myocardium is safe.
Goodchild
Traci
T
AC Therapeutics, 3155 Northwoods Place, Norcross, GA 30017, USA. tgoodchild@acrionline.org
Pang
Wenxin
W
Tondato
Fernando
F
Cui
Jianhua
J
Otsuka
Yoritaka
Y
Frowein
Steve
S
Ungs
Mark
M
Robinson
Keith
K
Poznansky
Mark
M
Chronos
Nicolas
N
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002364:Caseins / Q000009:adverse effects; D002453:Cell Cycle; D002454:Cell Differentiation; D002908:Chronic Disease; D052276:Creatine Kinase, BB Form / Q000097:blood; D052279:Creatine Kinase, MB Form / Q000097:blood; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D005434:Flow Cytometry; D020100:Hydrogels / Q000009:adverse effects; D017202:Myocardial Ischemia / Q000097:blood / Q000139:chemically induced / Q000401:mortality / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D011183:Postoperative Complications / Q000209:etiology; D015996:Survival Rate; D013552:Swine; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D014182:Transplantation, Autologous; D018487:Ventricular Dysfunction, Left / Q000601:surgery
D015415:Biomarkers; D002364:Caseins; D020100:Hydrogels; C009719:ameroid; D052276:Creatine Kinase, BB Form; D052279:Creatine Kinase, MB Form