MacDonald Derek J, Luo Jun, Saito Takayuki, Duong Minh, Bernier Pierre-Luc, Chiu Ray C J, Shum-Tim Dominique
Division of Cardiothoracic Surgery, McGill University Health Center, Montreal, Quebec, Canada.
J Thorac Cardiovasc Surg. 2005 Oct;130(4):1114-21. doi: 10.1016/j.jtcvs.2005.04.033.
It has been reported that unmatched adult bone marrow stromal cells could be tolerated by immune-competent allotransplant or xenotransplant recipients under various conditions. This study examined whether xenogeneic bone marrow stromal cells implanted immediately after myocardial infarction can survive and differentiate, attenuating deterioration in left ventricular function.
In groups I and II (n = 34), myocardial infarctions were created in immunocompetent adult Lewis rats by proximal left coronary artery ligation. In group I, 3 x 10(6)lacZ-labeled mouse bone marrow stromal cells were immediately injected into the peri-infarct area of the left ventricle, whereas in group II, only culture medium was injected. There were 10 early and 4 late deaths. At 4 weeks after injection, hearts were stained for beta-galactosidase and troponin IC. In groups IIIA and IIIB, lacZ-labeled mouse skin fibroblasts were implanted into rat myocardium (n = 10 each) with and without left coronary artery ligation, respectively, and the rats were killed serially. In group IV, animals underwent sham surgery (n = 5, no deaths). At 4 weeks, surviving rats in groups I, II, and IV (n = 10, n = 10, and n = 5, respectively) underwent blinded transthoracic echocardiography for ventricular function studies.
In group I, labeled mouse-derived bone marrow stromal cells were found within rat myocardium that stained positively for troponin IC 4 weeks after implantation. Functionally, mean left ventricular ejection fraction (P = .007), stroke volume (P = .03), and fractional shortening (P = .02) were all significantly higher in group I than in group II. In groups IIIA and IIIB, mouse fibroblasts induced cellular infiltration with rapid loss of donor cells. No labeled cells were found after 4 days. In group IV, there was no change in cardiac function.
Xenogeneic bone marrow stromal cells implanted into acutely ischemic myocardium induced by coronary artery ligation were immunologically tolerated, survived and differentiated, resulting in a cardiac chimera which improved left ventricular function. This unique immunologic tolerance may suggest the feasibility of using bone marrow stromal cells as universal donor cells.
据报道，在各种条件下，免疫健全的同种异体移植或异种移植受者可耐受不匹配的成年骨髓基质细胞。本研究检测心肌梗死后立即植入的异种骨髓基质细胞是否能够存活并分化，减轻左心室功能恶化。
在I组和II组（n = 34）中，通过结扎左冠状动脉近端在免疫健全的成年Lewis大鼠中制造心肌梗死。在I组中，将3×10(6)个用lacZ标记的小鼠骨髓基质细胞立即注射到左心室梗死周边区域，而在II组中，仅注射培养基。有10只早期死亡和4只晚期死亡。注射后4周，对心脏进行β-半乳糖苷酶和肌钙蛋白IC染色。在IIIA组和IIIB组中，分别在有和无左冠状动脉结扎的情况下，将用lacZ标记的小鼠皮肤成纤维细胞植入大鼠心肌（每组n = 10），并对大鼠进行连续处死。在IV组中，动物接受假手术（n = 5，无死亡）。4周时，I组、II组和IV组的存活大鼠（分别为n = 10、n = 10和n = 5）接受盲法经胸超声心动图检查以评估心室功能。
在I组中，植入后4周在大鼠心肌内发现标记的小鼠来源骨髓基质细胞，其肌钙蛋白IC染色呈阳性。在功能上，I组的平均左心室射血分数（P = .007）、每搏输出量（P = .03）和缩短分数（P = .02）均显著高于II组。在IIIA组和IIIB组中，小鼠成纤维细胞诱导细胞浸润，供体细胞迅速丢失。4天后未发现标记细胞。在IV组中，心脏功能无变化。
植入由冠状动脉结扎诱导的急性缺血心肌中的异种骨髓基质细胞在免疫上被耐受，存活并分化，形成改善左心室功能的心脏嵌合体。这种独特的免疫耐受性可能提示使用骨髓基质细胞作为通用供体细胞的可行性。
