Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets

Synergistic effects of injection of bone marrow cells into both portal vein and bone marrow on tolerance induction in transplantation of allogeneic pancreatic islets
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DOI:
10.1038/sj.bmt.1705500
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发表时间:
2006-11-01
影响因子:
4.8
通讯作者:
Ikehara, S.
Ikehara, S.
中科院分区:
医学3区
文献类型:
--
作者:
Ikebukuro, K.;Adachi, Y.;Ikehara, S.

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我们建立了一种新的同种异体胰岛(PI)移植方法:低剂量照射后经门静脉(PV)同时移植PI和骨髓细胞(BMCs)。在本研究中,我们比较了这种方法与骨髓内(IBM)-骨髓移植(BMT),并与两种方法的组合。链脲佐菌素(STZ)诱导的糖尿病受体大鼠Fischer 344(F344,RT 1A(1),RT 1B(1))在移植前1天接受辐射。通过PV将Brown Norway大鼠的PI(BN,RT 1A(n),RT 1B(n))移植到糖尿病F344大鼠的肝脏中。将来自BN大鼠的BMC注射到受体的骨髓(IBM)中、PV或静脉注射(IV)或通过PV加IBM(PV+IBM)的同时组合。比较了9 Gy +IBM组移植物存活率(10/10接受),“9 Gy + PV”(7/10接受),“9戈伊+ IV”(0/7接受),“9戈伊+ PV + IBM”(8/8接受),“8.5戈伊+ IBM”(4/9接受),“8.5戈伊+ PV”“8.5戈伊+IV”(0/7接受)、“8.5戈伊+ PV + IBM”(9/12接受)、“8戈伊+ IBM”(2/10接受)和“8戈伊+ PV + IBM”(2/8接受)。正如我们先前报道的,PV-BMT比IV-BMT更有效地诱导接受同种异体PI。然而,IBM-BMT比PV-BMT需要更少的预处理。(PV+ IBM)-BMT被发现在诱导同种异体PI的接受方面最有效。这些结果表明,异基因PI移植结合(PV + IBM)- BMT可能成为一个可行的策略。
We have established a new method for allogeneic pancreatic islet ( PI) transplantation: relatively low doses of irradiation followed by simultaneous transplantation of PIs and bone marrow cells (BMCs) via the portal vein (PV). In the present study, we have compared this method with intra-bone marrow (IBM)-bone marrow transplantation (BMT), and with a combination of both methods. Streptozotocin (STZ)-induced diabetic-recipient rats, Fischer 344 ( F344, RT1A(1), RT1B(1)), were irradiated 1 day before transplantation. PIs of Brown Norway rats (BN, RT1A(n), RT1B(n)) were transplanted into the liver of the diabetic F344 rats via the PV. BMCs from BN rats were injected into the recipients' bone marrow ( IBM), PV or intravenously (IV) or by a simultaneous combination of PV plus IBM (PV+IBM). We compared graft survival among the groups of '9Gy+IBM'(10/10 accepted), '9Gy + PV'( 7/10 accepted), '9 Gy + IV'(0/7 accepted), '9 Gy + PV + IBM'(8/8 accepted), '8.5 Gy+ IBM'(4/9 accepted), '8.5 Gy + PV'(0/7 accepted), '8.5 Gy + IV'(0/7 accepted), '8.5 Gy + PV + IBM'(9/12 accepted), '8 Gy + IBM' (2/10 accepted) and '8 Gy + PV + IBM' (2/8 accepted). As we reported previously, PV-BMT is more effective in inducing the acceptance of allogeneic PIs than IV-BMT. However, IBM-BMT requires less pretreatment than PV-BMT. (PV + IBM)-BMT was found to be the most effective in inducing the acceptance of allogeneic PIs. These results suggest that allogeneic PI-transplantation in conjunction with (PV + IBM)- BMT could become a viable strategy.