Comparison of parathyroid hormone and G-CSF treatment after myocardial infarction on perfusion and stem cell homing.
Mobilization of stem cells by granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI); however, clinical trials failed to be effective. In search for alternative cytokines, parathyroid hormone (PTH) was recently shown to promote cardiac repair by enhanced neovascularization and cell survival. To compare the impact of the two cytokines G-CSF and PTH on myocardial perfusion, mice were noninvasively and repetitively investigated by pinhole single-photon emission computed tomography (SPECT) after MI. Mobilization and homing of bone marrow-derived stem cells (BMCs) was analyzed by fluorescence-activated cell sorter (FACS) analysis. Mice (C57BL/6J) were infarcted by left anterior descending artery ligation. PTH (80 mug/kg) and G-CSF (100 mug/kg) were injected for 5 days. Perfusion defects were determined by (99m)Tc-sestamibi SPECT at days 6 and 30 after MI. The number of BMCs characterized by Lin(-)/Sca-1(+)/c-kit(+) cells in peripheral blood and heart was analyzed by FACS. Both G-CSF and PTH treatment resulted in an augmented mobilization of BMCs in the peripheral blood. Contrary to G-CSF and controls, PTH and the combination showed significant migration of BMCs in ischemic myocardium associated with a significant reduction of perfusion defects from day 6 to day 30. A combination of both cytokines had no additional effects on migration and perfusion. In our preclinical model, SPECT analyses revealed the functional potential of PTH reducing size of infarction together with an enhanced homing of BMCs to the myocardium in contrast to G-CSF. A combination of both cytokines did not improve the functional outcome, suggesting clinical applications of PTH in ischemic heart diseases.
Huber
Bruno C
BC
Department of Internal Medicine I, Ludwig-Maximilians-University, Campus Grosshadern, Marchioninistrasse 15, Munich, Germany.
Fischer
Rebekka
R
Brunner
Stefan
S
Groebner
Michael
M
Rischpler
Christoph
C
Segeth
Alexander
A
Zaruba
Marc M
MM
Wollenweber
Tim
T
Hacker
Marcus
M
Franz
Wolfgang-Michael
WM
D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D010477:Perfusion; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D016207:Cytokines; D010281:Parathyroid Hormone; D019275:Radiopharmaceuticals; D016179:Granulocyte Colony-Stimulating Factor; D017256:Technetium Tc 99m Sestamibi