在闭塞性细支气管炎小鼠模型中，采用减低剂量预处理的同时进行供体骨髓细胞移植可防止气管同种异体移植闭塞。

Simultaneous donor marrow cell transplantation with reduced intensity conditioning prevents tracheal allograft obliteration in a bronchiolitis obliterans murine model.

作者信息

Nusair Samir, Or Reuven, Junadi Samer, Amir Gail, Breuer Raphael

机构信息

Lung Cellular and Molecular Biology Laboratory, Hadassah University Hospital, PO Box 12072, Jerusalem, Israel, 91120.

出版信息

Chest. 2005 Dec;128(6):4024-9. doi: 10.1378/chest.128.6.4024.

DOI:10.1378/chest.128.6.4024

PMID:16354876

Abstract

STUDY OBJECTIVES

Prolonged survival of transplanted kidney or liver allografts has been associated with prolonged chimerism resulting from donor-origin leukocytes carried within the allograft parenchyma. The present study, performed in a murine model, examined whether simultaneous administration of donor bone marrow cells after reduced intensity conditioning allows acceptance of heterotopic tracheal allografts and prevents the formation of the airway fibroproliferative lesion, which mimics bronchiolitis obliterans (BO).

METHODS

Allogeneic tracheal allografts from C57BL/6 mice were grafted subcutaneously into BALB/c mice (n = 6) [day 0]. Conditioning consisted of total lymphoid irradiation (200 cGy) at day - 1, donor marrow cells (3 x 10(7)) administered IV on day 0, intraperitoneal cyclophosphamide (200 mg/kg) on day 1 to eliminate alloreactive marrow cells, followed by a repeated dose of donor marrow cells on day 2. Control groups consisted of one group (n = 4) that underwent similar conditioning without donor marrow cells, and another group (n = 4) that received syngeneic BALB/c marrow cells. None of these groups were administered maintenance immunosuppression. Grafts were harvested and histopathology findings were evaluated semiquantitatively at day 28, day 55, and day 95.

RESULTS

Tracheal allografts from donor marrow cell recipients still maintained a patent airway with intact airway epithelium at 95 days after transplant. However, grafts from control animals not receiving donor marrow cells or mice administered syngeneic marrow cells had lumen obliteration by 28 days after transplant. Chimerism in animals receiving allogeneic bone marrow was confirmed. Graft vs host disease did not develop in animals receiving allogeneic marrow cells.

CONCLUSIONS

Further investigation may verify this approach to be applicable for the prevention of posttransplantation BO.

摘要

研究目的

移植肾或肝同种异体移植物的长期存活与同种异体移植物实质内携带的供体来源白细胞导致的长期嵌合现象有关。本研究在小鼠模型中进行，探讨在减低预处理强度后同时给予供体骨髓细胞是否能使异位气管同种异体移植物被接受，并防止气道纤维增生性病变的形成，该病变类似于闭塞性细支气管炎（BO）。

方法

将来自C57BL/6小鼠的同种异体气管移植物皮下移植到BALB/c小鼠（n = 6）体内[第0天]。预处理包括在第 - 1天进行全身淋巴照射（200 cGy），在第0天静脉注射供体骨髓细胞（3×10⁷），在第1天腹腔注射环磷酰胺（200 mg/kg）以清除同种反应性骨髓细胞，随后在第2天重复给予供体骨髓细胞。对照组包括一组（n = 4）接受类似预处理但未给予供体骨髓细胞的小鼠，以及另一组（n = 4）接受同基因BALB/c骨髓细胞的小鼠。这些组均未给予维持性免疫抑制。在第28天、第55天和第95天收获移植物，并对组织病理学结果进行半定量评估。