Keratinocyte growth factor administered before conditioning ameliorates graft-versus-host disease after allogeneic bone marrow transplantation in mice
Keratinocyte growth factor administered before conditioning ameliorates graft-versus-host disease after allogeneic bone marrow transplantation in mice
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DOI：
10.1182/blood.v92.10.3960.422k29_3960_3967
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发表时间：
1998-11-15
期刊：
影响因子：
20.3
通讯作者：
Blazar, BR
中科院分区：
文献类型：
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作者：
Panoskaltsis-Mortari, A;Lacey, DL;Blazar, BR
角质形成细胞生长因子(KGF)在组织修复和伤口愈合中起重要作用，它的应用可以消除化学和辐射引起的啮齿动物组织损伤。在已建立的小鼠异基因骨髓移植(BMT)模型中，我们研究了KGF作为预防移植物抗宿主病(GVHD)引起的组织损伤、发病率和死亡率的治疗剂。B10.BR(H2(K))受体小鼠接受致死性照射后，移植C57BL/6(H2(B))骨髓(BM)和脾细胞(BMS)作为GVHD的T细胞来源。BMT前6、5、4天皮下注射KGF(5 mg/kg/d)的小鼠存活率高于未接受KGF治疗的小鼠(P=0.0027)。环磷酰胺(Cy)是全身照射(TBI)方案中的常见成分，于骨髓移植前-3天和-2天分别以120 mg/kg/d的剂量给其他组小鼠腹腔注射。接受KGF治疗的小鼠的存活率再次高于未接受KGF治疗的小鼠(P=.00086)。然而，接受TBI或Cy/TBI EMS的KGF治疗的受者并不是无GVHD。与BM组相比，体重下降。在骨髓移植后38天的观察期内，对GVHD靶组织进行组织学评估。KGF可改善移植物抗宿主病(GVHD)引起的肝、皮肤和肺的组织损伤(在一些受体中完全)，对脾、结肠和回肠的组织损伤也是中等程度的，即使在Cy条件下也是如此。这些研究表明，在条件化前完成的KGF给药，具有作为抗GVHD治疗剂的潜力。(C)1998年由美国血液病学会主办。
Keratinocyte growth factor (KGF) is important in tissue repair and wound healing and its administration can abrogate chemical- and radiation-induced tissue damage in rodents. We investigated KGF as a therapeutic agent for the prevention of graft-versus-host disease (GVHD)-induced tissue damage, morbidity, and mortality in an established murine allogeneic bone marrow transplantation (BMT) model. B10.BR (H2(k)) recipient mice were lethally irradiated and transplanted with C57BL/6 (H2(b)) bone marrow (BM) with spleen cells (BMS) as a source of GVHD-causing T cells. KGF-treated mice (5 mg/kg/d subcutaneously days -6, -5, and -4 pre-BMT) receiving EMS exhibited better survival than those not receiving KGF (P = .0027). Cyclophosphamide (cy), a common component of total body irradiation (TBI)containing regimens, was administered to other cohorts of mice at a dose of 120 mg/kg/d intraperitoneally on days -3 and -2 before BMT. KGF-treated mice again exhibited a better survival rate than those not receiving KGF (P = .00086). However, KGF-treated recipients receiving TBI or Cy/TBI EMS were not GVHD-free. as shown by lower body weights compared with BM groups. GVHD target tissues were assessed histologically during a 38-day post-BMT observation period. KGF ameliorated GVHD-induced tissue damage in the liver, skin, and lung (completely in some recipients) and moderately so in the spleen, colon, and ileum, even with Cy conditioning. These studies demonstrate that KGF administration, completed before conditioning, has potential as an anti-GVHD therapeutic agent. (C) 1998 by The American Society of Hematology.