Treatment of streptozotocin-induced diabetes mellitus in rats by transplantation of islet cells from two major histocompatibility complex disparate rats in combination with intra bone marrow injection of allogeneic bone marrow cells

Treatment of streptozotocin-induced diabetes mellitus in rats by transplantation of islet cells from two major histocompatibility complex disparate rats in combination with intra bone marrow injection of allogeneic bone marrow cells
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DOI:
10.1097/01.tp.0000155500.17348.94
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发表时间:
2005-03-27
期刊:
影响因子:
6.2
通讯作者:
Ikehara, S
Ikehara, S
中科院分区:
医学2区
文献类型:
--
作者:
Taira, M;Inaba, M;Ikehara, S

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背景我们已经建立了一种新的方法,用于移植从两种不同品系的大鼠获得的同种异体胰岛,结合新开发的骨髓移植(BMT)方法,其中骨髓细胞(BMCs)直接注射到骨髓腔中(骨髓内BMT [IBM-BMT])。链脲佐菌素诱导的糖尿病Brown Norway(BN:RT 1A(n))大鼠注射氟达拉滨,用5.0 GyX 2照射,然后将来自两种同种异体大鼠品系Fischer 344(F344:RT 1A(1))和PVG(PVG:RTIA(c))的BMC直接注射到骨髓腔(IBM-BMT)。同时取F344和PVG大鼠约600个胰岛混合后经门静脉移植入肝脏。AD接受治疗的受体在治疗后30天显示正常。两种供者型细胞均能完全重建血淋巴样细胞,并诱导对F344和PVG主要组织相容性复合物(MHQ)决定簇的免疫耐受。从两个MHC不同的供体的PI移植与IBM-BMT组合完全实现,导致血糖水平的改善和糖尿病的改善。
Background. We have established a new method for the transplantation of allogeneic pancreatic islets obtained from two different rat strains in combination with a newly developed bone marrow transplantation (BMT) method in which bone marrow cells (BMCs) are directly injected into the bone marrow cavity (intra bone marrow BMT [IBM-BMT]).Methods. Streptozotocin-induced diabetic Brown Norway (BN: RT1A(n)) rats were injected with fludarabine, irradiated with 5.0 GyX2, and BMCs from two allogeneic rat strains, Fischer 344 (F344: RT1A(1)) and PVG (PVG: RTIA(c)), were then directly injected into the bone marrow cavity (IBM-BMT). Simultaneously, approximately 600 pancreatic islets (PIs) from F344 and PVG rats were mixed and transplanted into the liver by way of the portal vein.Results. AD the recipients thus treated showed normoglycemia 30 days after the treatment. Hematolymphoid cells were completely reconstituted with the two donor-type cells, and immunologic tolerance to F344 and PVG major histocompatibility complex (MHQ determinants were induced.Conclusions. The transplantation of PIs from two MHC-disparate donors was completely achieved in combination with IBM-BMT, resulting in the improvement of blood glucose levels and the amelioration of diabetes mellitus.