Bhakta Shyam, Greco Nicholas J, Finney Marcie R, Scheid Paul E, Hoffman Robert D, Joseph Matthew E, Banks Jason J, Laughlin Mary J, Pompili Vincent J
Division of Cardiology, Department of Medicine, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, Ohio, USA.
J Invasive Cardiol. 2006 May;18(5):212-8.
Intracoronary mononuclear cell therapy may produce angiogenesis in chronic myocardial ischemia. Potential complications include periprocedural infarction secondary to: reduced coronary blood flow; hyperviscosity from the cell preparation; or microvascular dysfunction. To date, no studies to evaluate these potential complications have been reported. The objective of this report was to study the safety and feasibility of intracoronary injections of autologous bone marrow mononuclear cells in a porcine chronic myocardial ischemia model.
Domestic pigs (n = 5) underwent ameroid cuff placement of the left circumflex artery. Bone marrow-derived mononuclear cells [15 x 10(6) cells] labeled with CM dioctadecyl tetramethylindocarbocyanine were given by intracoronary injection. Animals were sacrificed, and hearts and vital organs were inspected grossly and by histopathology, and bone marrow underwent immunofluorescence microscopy.
Troponin I levels, gross inspection and histopathology did not reveal evidence of myocardial infarction. Labeled cells were observed in perivascular structures in myocardium at the injection site in all animals and in the spleen from one animal. Bone marrow aspirates indicated labeled cells.
Intracoronary injection of autologous mononuclear cells in a porcine chronic myocardial ischemia model appears safe. Intracoronary injection resulted in cell localization in the perivascular areas of myocardium supplied by the injected vessel. Cell localization was observed only in the spleen in just one animal. Labeled cells were identified in bone marrow aspirates from three animals following injection, suggesting a role for bone marrow engraftment and repopulation as a possible mechanism for progenitor cell localization in myocardium.
冠状动脉内单核细胞治疗可能在慢性心肌缺血中产生血管生成。潜在并发症包括继发于以下情况的围手术期梗死：冠状动脉血流减少；细胞制剂导致的血液高黏滞度；或微血管功能障碍。迄今为止，尚无评估这些潜在并发症的研究报道。本报告的目的是在猪慢性心肌缺血模型中研究冠状动脉内注射自体骨髓单核细胞的安全性和可行性。
对5头家猪进行左旋支动脉的阿霉素袖带植入。通过冠状动脉内注射给予用CM二辛基四甲基吲哚碳菁标记的骨髓源性单核细胞[15×10(6)个细胞]。处死动物，对心脏和重要器官进行大体检查和组织病理学检查，并对骨髓进行免疫荧光显微镜检查。
肌钙蛋白I水平、大体检查和组织病理学检查均未发现心肌梗死的证据。在所有动物注射部位的心肌血管周围结构以及1只动物的脾脏中观察到标记细胞。骨髓穿刺显示有标记细胞。
在猪慢性心肌缺血模型中冠状动脉内注射自体单核细胞似乎是安全的。冠状动脉内注射导致细胞定位于注射血管所供应心肌的血管周围区域。仅在1只动物的脾脏中观察到细胞定位。注射后在3只动物的骨髓穿刺物中鉴定出标记细胞，提示骨髓植入和再填充可能是祖细胞定位于心肌的一种机制。
