Transcoronary delivery of bone marrow cells to the infarcted murine myocardium: feasibility, cellular kinetics, and improvement in cardiac function.
Efficient strategies for labelling and delivery of bone marrow derived stem cells (BMCs) are required to elucidate the cellular kinetics and therapeutic effects after BMC transfer for myocardial infarction (MI). Lineage negative (lin-) BMCs, labelled ex vivo in a simple procedure with the cell tracker dye tetramethyl-rhodamine (TAMRA), were reliably detected by fluorescence microscopy with higher specificity than retroviral enhanced green fluorescence protein (EGFP) marking and detection. Only few cells entered the ischemic myocardium after intravenous (i.v.) application, but this number increased more than 18-fold after transcoronary delivery. Time course and kinetic analysis over 12 h revealed that myocardial colonization seems to be a biphasic process of first order decay with different elimination half-lives. Most cells are eliminated rapidly during the first 2 h (t1/2 40 min), but the remaining cells are retained significantly longer in the ischemic heart (t1/2 5.2 h). In contrast, BMC colonization of the spleen increased rather in a linear fashion. Although transcoronary BMC transfusion did not alter infarct size, it increased capillary density in the infarct border zone and improved LV function 4 weeks after MI. In conclusion, BMCs delivered by transcoronary injection increase capillary density and improve LV function after MI although homing to the ischemic heart is only transient.
Templin
Christian
C
Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. templin.christian@mh-hannover.de
Kotlarz
Daniel
D
Marquart
Frederik
F
Faulhaber
Joerg
J
Brendecke
Vanessa
V
Schaefer
Arnd
A
Tsikas
Dimitrios
D
Bonda
Tomasz
T
Hilfiker-Kleiner
Denise
D
Ohl
Lars
L
Naim
Hassan Y
HY
Foerster
Reinhold
R
Drexler
Helmut
H
Limbourg
Florian P
FP
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D002452:Cell Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000628:therapy*; D015425:Myocardial Reperfusion; D012235:Rhodamines; D033581:Stem Cell Transplantation / Q000379:methods*
C114557:5-carboxytetramethylrhodamine succinimidyl ester; D012235:Rhodamines