Department of Cardiothoracic Surgery, School of Medicine, Stanford University, Stanford, CA, USA.
Division of Blood and Marrow Transplantation, Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
J Cardiovasc Transl Res. 2018 Aug;11(4):274-284. doi: 10.1007/s12265-017-9772-y. Epub 2018 Feb 21.
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.
基质细胞衍生因子 1-α（SDF）是一种强大的骨髓趋化因子，能够招募循环祖细胞到受损组织。SDF 具有已知的血管生成能力，但骨髓来源的细胞对组织再生的贡献仍存在争议。DsRed 转基因供体的骨髓被移植到心肌梗死（MI）后的受体中，以谱系追踪循环细胞。MI 后给予 SDF，评估骨髓源性细胞的募集和可塑性。SDF 治疗可改善 MI 后心室功能、边缘区血管密度和 CD31+细胞频率。观察到骨髓来源的内皮细胞；这些细胞通过细胞融合和转分化产生。循环细胞也采用心肌细胞命运，但这种情况极为罕见，几乎完全是由细胞融合引起的。SDF 对采用非造血命运的循环细胞的比例没有显著影响。深入了解循环细胞的调控机制对于充分发挥细胞因子治疗的潜力至关重要。
