Guo Changfa, Haider Husnain Kh, Wang Chunsheng, Tan Ru-San, Shim Winston S N, Wong Philip, Sim Eugene K W
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Ann Thorac Surg. 2008 Dec;86(6):1841-8. doi: 10.1016/j.athoracsur.2008.08.038.
We sought to compare host immune cell kinetics, survival profile of donor skeletal myoblasts, and skeletal myoblast graft efficacy after autologous and allogeneic skeletal myoblast transplantation into a rat model of myocardial infarction.
One week after myocardial infarction, 128 animals were divided into four groups: group 1 (n = 24, receiving medium only), group 2 (n = 24, receiving medium and cyclosporine), group 3 (n = 40, autologous skeletal myoblast transplantation), and group 4 (n = 40, allogeneic skeletal myoblast transplantation with cyclosporine treatment). Rats were euthanized 10 minutes, 1 day, and 4, 7, and 28 days later. Host immune cell kinetics were assessed by immunohistochemical studies for macrophages, and CD4+ and CD8+ lymphocytes. Donor skeletal myoblast survival was confirmed by tracking prelabeled signals, and quantified by beta-gal assay. Heart function was evaluated by echocardiography.
A transient immune cell infiltration was demonstrated in group 3, with macrophage infiltration on day 1 and day 4, CD8+ cell infiltration on day 4 and day 7, and CD4+ cell infiltration on day 4. In group 4, immunocyte infiltration was slightly more severe than that in group 3. Automyoblasts and allomyoblasts showed no significant difference of survival from day 1 to day 7 (p > 0.10); however, on day 28, automyoblasts showed better survival than allomyoblasts (p < 0.05). Transplantation of allomyoblasts increased systolic heart function and limited heart dilation after myocardial injury to a similar degree as automyoblasts (p > 0.10).
The use of allomyoblasts is feasible and effective for cardiac repair with immunosuppressive treatment as compared with automyoblasts.
我们试图比较自体和异体骨骼肌成肌细胞移植到大鼠心肌梗死模型后宿主免疫细胞动力学、供体骨骼肌成肌细胞的存活情况以及骨骼肌成肌细胞移植的疗效。
心肌梗死后1周,将128只动物分为四组:第1组(n = 24,仅接受培养基),第2组(n = 24,接受培养基和环孢素),第3组(n = 40,自体骨骼肌成肌细胞移植),第4组(n = 40,异体骨骼肌成肌细胞移植并接受环孢素治疗)。在10分钟、1天、4天、7天和28天后对大鼠实施安乐死。通过对巨噬细胞以及CD4 +和CD8 +淋巴细胞进行免疫组织化学研究来评估宿主免疫细胞动力学。通过追踪预先标记的信号来确认供体骨骼肌成肌细胞的存活情况,并通过β-半乳糖苷酶测定进行定量。通过超声心动图评估心脏功能。
第3组出现短暂的免疫细胞浸润,第1天和第4天有巨噬细胞浸润,第4天和第7天有CD8 +细胞浸润,第4天有CD4 +细胞浸润。在第4组中,免疫细胞浸润比第3组略严重。自体成肌细胞和异体成肌细胞从第1天到第7天的存活情况无显著差异(p>0.10);然而,在第28天,自体成肌细胞的存活情况优于异体成肌细胞(p<0.05)。异体成肌细胞移植对心肌损伤后的心脏收缩功能增强和心脏扩张受限的程度与自体成肌细胞相似(p>0.10)。
与自体成肌细胞相比,异体成肌细胞在免疫抑制治疗下用于心脏修复是可行且有效的。