Nephrology Department, Rouen University Hospital, Rouen, France.
J Surg Res. 2011 Jun 1;168(1):143-8. doi: 10.1016/j.jss.2009.10.018. Epub 2009 Nov 4.
Transplant arteriosclerosis is characterized by intraluminal obstructive proliferation occurring in response to immune-mediated arterial wall injury. Cell therapy with vascular progenitor cells have been suggested to repair intimal lesions following endothelial injury. The aim of the current study was to assess the effects of autologous bone marrow cell direct transfer and of Fucan-mobilization bone marrow-derived progenitor cells on intimal thickening in vascular grafts.
Aortic allografts were performed in Brown Norway (BN) and Lewis (LEW) rats. Cell therapy was performed by injection of two doses of 10 million LEW bone marrow mononuclear cells to recipient LEW following aortic grafting. Fucan, a low molecular weight sulfated polysaccharide (LMWF) was used to mobilize bone marrow-derived progenitor cells. Five groups of 10 rats included: untreated isografts (BN to BN), untreated allografts, and three allografted groups, respectively, treated by fucan therapy, cell therapy, or cell and fucan therapy. Aorta were studied by morphometric analysis at 30 d.
In the absence of treatment, intimal thickening was greater in allograft than in isograft groups (299±50 versus 3.5±1.7 μm, P<0.001). Cell therapy alone, fucan therapy alone, and the combined treatment were shown to prevent intimal thickening in allografts (5.1±1.7, 6.1±2.3, 4.1±2.5, versus 299±50 μm respectively, P<0.001). In the three treated groups, the intimal lining was a single layer of endothelial cells expressing CD34 positive, endothelial nitric oxide synthase (eNOS) positive, and Ox3 specific-recipient monoclonal antibody positive.
These results provide the proof of concept of recipient syngenic bone-marrow cell therapy for the prevention of chronic vasculopathy.
移植性动脉硬化的特征是在免疫介导的动脉壁损伤后，管腔内出现阻塞性增生。血管祖细胞的细胞治疗被认为可以修复内皮损伤后的内膜病变。本研究旨在评估自体骨髓细胞直接转移和 Fucan 动员骨髓源性祖细胞对血管移植物内膜增厚的影响。
在 Brown Norway（BN）和 Lewis（LEW）大鼠中进行主动脉同种异体移植。细胞治疗是通过在主动脉移植后向受体 LEW 注射两剂 1000 万个 LEW 骨髓单核细胞来进行的。Fucan 是一种低分子量硫酸多糖（LMWF），用于动员骨髓源性祖细胞。包括 10 只大鼠的五组：未处理的同种异体移植（BN 至 BN）、未处理的同种异体移植和三个同种异体移植组，分别用 Fucan 治疗、细胞治疗或细胞和 Fucan 治疗。在 30 天时通过形态计量分析研究主动脉。
在没有治疗的情况下，同种异体移植中的内膜增厚大于同种异体移植组（299±50 与 3.5±1.7μm，P<0.001）。单独细胞治疗、单独 Fucan 治疗和联合治疗均能预防同种异体移植中的内膜增厚（5.1±1.7、6.1±2.3、4.1±2.5，分别与 299±50μm，P<0.001）。在三个治疗组中，内膜衬里是单层表达 CD34 阳性、内皮型一氧化氮合酶（eNOS）阳性和 Ox3 特异性受体单克隆抗体阳性的内皮细胞。
这些结果为预防慢性血管病的受体同基因骨髓细胞治疗提供了概念验证。
