1. SDF 1-alpha Attenuates Myocardial Injury Without Altering the Direct Contribution of Circulating Cells.
- Author
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Goldstone AB, Burnett CE, Cohen JE, Paulsen MJ, Eskandari A, Edwards BE, Ingason AB, Steele AN, Patel JB, MacArthur JW, Shizuru JA, and Woo YJ
- Subjects
- Animals, Bone Marrow Transplantation, Cell Differentiation, Cells, Cultured, Coronary Vessels metabolism, Coronary Vessels pathology, Disease Models, Animal, Endothelium, Vascular metabolism, Endothelium, Vascular pathology, Immunohistochemistry, Mice, Inbred C57BL, Mice, Transgenic, Myocardial Infarction physiopathology, Myocardial Infarction therapy, Myocytes, Cardiac pathology, Ventricular Function, Left, Chemokine CXCL12 metabolism, Myocardial Infarction metabolism, Myocytes, Cardiac metabolism
- Abstract
Stromal cell-derived factor 1-alpha (SDF) is a potent bone marrow chemokine capable of recruiting circulating progenitor populations to injured tissue. SDF has known angiogenic capabilities, but bone marrow-derived cellular contributions to tissue regeneration remain controversial. Bone marrow from DsRed-transgenic donors was transplanted into recipients to lineage-trace circulating cells after myocardial infarction (MI). SDF was delivered post-MI, and hearts were evaluated for recruitment and plasticity of bone marrow-derived populations. SDF treatment improved ventricular function, border zone vessel density, and CD31+ cell frequency post-MI. Bone marrow-derived endothelial cells were observed; these cells arose through both cell fusion and transdifferentiation. Circulating cells also adopted cardiomyocyte fates, but such events were exceedingly rare and almost exclusively resulted from cell fusion. SDF did not significantly alter the proportion of circulating cells that adopted non-hematopoietic fates. Mechanistic insight into the governance of circulating cells is essential to realizing the full potential of cytokine therapies.
- Published
- 2018
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