CD34-positive cells exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells.
BACKGROUND
We compared the therapeutic potential of purified mobilized human CD34+ cells with that of mobilized total mononuclear cells (tMNCs) for the preservation/recovery of myocardial tissue integrity and function after myocardial infarction (MI).


RESULTS
CD34+ cells were purified from peripheral blood tMNCs of healthy volunteers by magnetic cell sorting after a 5-day administration of granulocyte colony-stimulating factor. Phosphate-buffered saline (PBS), 5x10(5) CD34+ cells/kg, 5x10(5) tMNCs/kg (low-dose MNCs [loMNCs]), or a higher dose of tMNCs (hiMNCs) containing 5x10(5) CD34+ cells/kg was transplanted intramyocardially 10 minutes after the induction of MI in athymic nude rats. Hematoxylin and eosin staining revealed that moderate to severe hemorrhagic MI on day 3 was more frequent in the hiMNC group than in the PBS and CD34+ cell groups. Immunostaining for human-specific CD45 revealed abundant distribution of hematopoietic/inflammatory cells derived from transplanted cells in the ischemic myocardium of the hiMNC group. Capillary density on day 28 was significantly greater in the CD34+ cell group (721.1+/-19.9 per 1 mm2) than in the PBS, loMNC, and hiMNC groups (384.7+/-11.0, 372.5+/-14.1, and 497.5+/-24.0 per 1 mm2) (P<0.01). Percent fibrosis area on day 28 was less in the CD34(+) cell group (15.6+/-0.9%) than in the PBS, loMNC, and hiMNC groups (26.3+/-1.2%, 27.5+/-1.8%, and 22.2+/-1.8%) (P<0.05). Echocardiographic fractional shortening on day 28 was significantly higher in the CD34+ cell group (30.3+/-0.9%) than in the PBS, loMNC, and hiMNC groups (22.7+/-1.5%, 23.4+/-1.1%, and 24.9+/-1.7%; P<0.05). Echocardiographic regional wall motion score was better preserved in the CD34+ cell group (21.8+/-0.5) than in the PBS, loMNC, and hiMNC groups (25.4+/-0.4, 24.9+/-0.4, and 24.1+/-0.6; P<0.05).


CONCLUSIONS
CD34+ cells exhibit superior efficacy for preserving myocardial integrity and function after MI than unselected circulating MNCs.
Kawamoto
Atsuhiko
A
Division of Cardiovascular Research, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass 02135, USA.
Iwasaki
Hiroto
H
Kusano
Kengo
K
Murayama
Toshinori
T
Oyamada
Akira
A
Silver
Marcy
M
Hulbert
Christine
C
Gavin
Mary
M
Hanley
Allison
A
Ma
Hong
H
Kearney
Marianne
M
Zak
Victor
V
Asahara
Takayuki
T
Losordo
Douglas W
DW
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation; D004452:Echocardiography; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D011184:Postoperative Period; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors; D014183:Transplantation, Heterologous; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D018952:Antigens, CD34