Orłowski Tadeusz M, Godlewska Ewa, Tarchalska Magda, Kinasiewicz Joanna, Antosiak Magda, Sabat Marek
Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland.
Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):180-4.
The aim of this study was to determine the influence activating of the recipient immune system on the function of microencapsulated islet xenografts.
MATERIAL/METHODS: The skin of WAG or Fisher rats and WAG free or encapsulated (APA) Langerhans islets were transplanted to healthy or to streptozotocin diabetic BALB/c mice. Skin grafts were performed following the method of Billingham and Medawar. Rat islets were isolated from pancreas by the Lacy and Kostianovsy method and encapsulated with calcium alginate-poly-L-lysine-alginate according to the 3-step coating method of Sun.
The transplantation of encapsulated WAG islets, despite activation of the host immune system, restored euglycemia for over 180 +/-100 days. A subsequent skin graft taken from the same donor was rejected in the second set mode, but euglycemia persisted. In diabetic recipients, impaired immune response was corrected by successful encapsulated islet transplantation. In diabetic mice, strong stimulation with 2-fold skin transplantation induced primary non-function of grafted islets despite their encapsulation.
The survival of an islet xenograft depends on the level of activation of the recipient immune system. The immune response of diabetic mice was impaired, but increased after post-transplant restitution of euglycemia. Microencapsulation sufficiently protected grafted islets, and remission of diabetes was preserved. However, after strong specific or non-specific stimulation of the host immune system, non-function of xenografted islets developed despite their encapsulation. Therefore, islet graft recipients should avoid procedures which could stimulate their immune systems. If absolutely necessary, the graft should be protected by exogenous insulin therapy at that time.
本研究的目的是确定受体免疫系统激活对微囊化胰岛异种移植物功能的影响。
材料/方法：将WAG或Fisher大鼠的皮肤以及WAG游离或微囊化（APA）的胰岛移植到健康或经链脲佐菌素诱导糖尿病的BALB/c小鼠体内。皮肤移植按照比林厄姆和梅达沃的方法进行。大鼠胰岛通过莱西和科斯季亚诺夫斯基的方法从胰腺中分离出来，并根据孙的三步包被法用海藻酸钙-聚-L-赖氨酸-海藻酸进行包囊。
尽管宿主免疫系统被激活，但微囊化WAG胰岛的移植使血糖恢复正常超过180±100天。随后取自同一供体的皮肤移植在二次移植模式下被排斥，但血糖正常状态持续存在。在糖尿病受体中，成功的微囊化胰岛移植纠正了受损的免疫反应。在糖尿病小鼠中，尽管胰岛被包囊，但两次皮肤移植的强烈刺激导致移植胰岛原发性无功能。
胰岛异种移植物的存活取决于受体免疫系统的激活水平。糖尿病小鼠的免疫反应受损，但在移植后血糖恢复正常后增强。微囊化充分保护了移植的胰岛，并维持了糖尿病的缓解。然而，在对宿主免疫系统进行强烈的特异性或非特异性刺激后，尽管胰岛被包囊，仍会出现异种移植胰岛无功能的情况。因此，胰岛移植受体应避免可能刺激其免疫系统的操作。如果绝对必要，此时应通过外源性胰岛素治疗来保护移植物。
