Signaling factors in stem cell-mediated repair of infarcted myocardium.
Myocardial infarction leads to scar formation and subsequent reduced cardiac performance. The ultimate therapy after myocardial infarction would pursue stem cell-based regeneration. The aim of stem cell-mediated cardiac repair embodies restoration of cardiac function by regeneration of healthy myocardial tissue, which is accomplished by neo-angiogenesis and cardiogenesis. A major reservoir of adult autologous stem cells distal from the heart is the bone marrow. Adequate regulation of signaling between the bone marrow, the peripheral circulation and the infarcted myocardium is important in orchestrating the process of mobilization, homing, incorporation, survival, proliferation and differentiation of stem cells, that leads to myocardial regeneration. In this review, we discuss key signaling factors, including cytokines, chemokines and growth factors, which are involved in orchestrating the stem cell driven repair process. We focus on signaling factors known for their mobilizing and chemotactic abilities (SDF-1, G-CSF, SCF, IL-8, VEGF), signaling factors that are expressed after myocardial infarction involved in the patho-physiological healing process (TNF-alpha, IL-8, IL-10, HIF-1alpha, VEGF, G-CSF) and signaling factors that are involved in cardiogenesis and neo-angiogenesis (VEGF, EPO, TGF-beta, HGF, HIF-1alpha, IL-8). The future therapeutic application and capacity of secreted factors to modulate tissue repair after myocardial infarction relies on the intrinsic potency of factors and on the optimal localization and timing of a combination of signaling factors to stimulate stem cells in their niche to regenerate the infarcted heart.
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, NL 9713 GZ Groningen, The Netherlands.
S
S
Vandervelde
M J A
MJ
van Luyn
R A
RA
Tio
M C
MC
Harmsen
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*
D006133:Growth Substances