Yang Ding-hua, Wu Meng-chao, Peng Min-hao, Tzakis Andreas
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, People's Liberation Army, Shanghai 200438, China.
Zhonghua Wai Ke Za Zhi. 2005 Jan 15;43(2):87-91.
To prolong murine heart allograft by modifying hematopoietic stem cells with virus interleukin-10 (vIL-10).
The recombinant of murine stem cell virus (MSCVneo) vIL-10 was composed of MSCVneo and vIL-10 cDNA and transduced hematopoietic stem cells from CBA (H-2(K)) mice's bone marrow in vitro. The transduced hematopoietic stem cells were transplanted into a syngenic CBA (H-2(K)) mouse with lethal irradiation (900 rad) in the same day through penis vein. The mouse's heterotopic heart transplantation was conducted using CBA (H-2(K)) mice as recipients, which vIL-10 in serum were positive by enzyme-linked immunosorbent assay, and donors hearts from C57BL/6 (H-2b) mice. Five animals in each group were sacrificed to test histopathology changes, the expression of interleukin (IL)-2, IL-4, IL-6, mIL-10, interferon (IFN)-gamma, inducible nitric oxide synthase (iNOS), B7-1, B7-2 and CD(4)(+) and CD(8)(+) T cells subset infiltration in heart transplants with reverse transcriptase polymerase chain reaction, immunohistochemistry and regular pathology.
Survival time of mice's allografts experimental group was (80.0 +/- 33.3) days. And survival time of control groups were (10.4 +/- 1.0) days, (11.6 +/- 1.1) days and (11.2 +/- 1.7) days, respectively (P < 0.01). Heart transplants from experimental group were characterized by sparse lymphocytes infiltration, mild endocarditis and vasculitis and preserved myocardial architecture, which had acute rejection of grade I. Cardiac allografts from other control groups developed severe cellular rejection with severe infiltrating lymphocytes, myocyte injury and necrosis, interstitial edema and hemorrhage, which had acute rejection of grade III. The expression of IL-2, INF-gamma, B7-1, B7-2 and iNOS mRNA in allografts in experimental group markedly down-regulated, whereas that in allografts in control groups markedly upregulated (P < 0.05). CD(4)(+) and CD(8)(+) T cell subsets infiltration in heart transplants from experimental group decreased, and that in control groups increased (P < 0.05).
Engineering Hematopoietic stem cells with vIL-10 can protect cardiac allografts from acute rejection and prolong cardiac allografts survival.
通过用病毒白细胞介素-10（vIL-10）修饰造血干细胞来延长小鼠心脏同种异体移植的存活时间。
小鼠干细胞病毒（MSCVneo）vIL-10重组体由MSCVneo和vIL-10 cDNA组成，体外转导CBA（H-2(K)）小鼠骨髓中的造血干细胞。转导后的造血干细胞于同日经阴茎静脉移植到经致死剂量照射（900拉德）的同基因CBA（H-2(K)）小鼠体内。以CBA（H-2(K)）小鼠为受体、C57BL/6（H-2b）小鼠心脏为供体进行小鼠异位心脏移植。每组处死5只动物，采用逆转录聚合酶链反应、免疫组织化学和常规病理学方法检测心脏移植组织的组织病理学变化、白细胞介素（IL）-2、IL-4、IL-6、mIL-10、干扰素（IFN）-γ、诱导型一氧化氮合酶（iNOS）、B7-1、B7-2以及CD(4)(+)和CD(8)(+) T细胞亚群浸润情况。
实验组小鼠同种异体移植心脏的存活时间为（80.0±33.3）天。对照组的存活时间分别为（10.4±1.0）天、（11.6±1.1）天和（11.2±1.7）天（P<0.01）。实验组心脏移植组织的特点为淋巴细胞浸润稀疏、轻度心内膜炎和血管炎，心肌结构保存，急性排斥反应为I级。其他对照组的心脏同种异体移植发生严重的细胞排斥反应，淋巴细胞大量浸润、心肌细胞损伤和坏死、间质水肿和出血，急性排斥反应为III级。实验组同种异体移植组织中IL-2、INF-γ、B7-1、B7-2和iNOS mRNA的表达明显下调，而对照组同种异体移植组织中的表达明显上调（P<0.05）。实验组心脏移植组织中CD(4)(+)和CD(8)(+) T细胞亚群浸润减少，对照组增加（P<0.05）。
用vIL-10改造造血干细胞可保护心脏同种异体移植免受急性排斥反应，延长心脏同种异体移植的存活时间。
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