Impact of bone marrow transplantation on type I diabetes
Impact of bone marrow transplantation on type I diabetes
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DOI：
10.1007/s002680020340
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发表时间：
2001-04-01
影响因子：
2.6
通讯作者：
Ildstad, ST
中科院分区：
文献类型：
--
作者：
Domenick, MA;Ildstad, ST
I型糖尿病是一种全身性自身免疫性疾病。越来越多的证据表明，自身免疫性疾病如I型糖尿病与骨髓造血干细胞（HSC）本身而不是其衍生物有关，通过骨髓移植（BMT）实现的HSC嵌合体可能通过两种方式影响I型糖尿病：第一，诱导对胰腺和胰岛细胞移植的耐受;第二，在发生终末并发症之前逆转自身免疫过程。将来自正常供体的骨髓移植到患有恶性血液病和并存的I型糖尿病的患者中，逆转了全身性糖尿病自身免疫过程。供体HSC也可用于诱导对胰岛细胞移植的供体特异性耐受。胰岛或全胰腺移植是治疗I型糖尿病最符合生理的方法，目前，这受到需要高剂量慢性非特异性免疫抑制以防止排斥反应的限制。尽管有这些药物，慢性排斥反应仍然是晚期移植物丢失的主要原因。供者特异性耐受消除了对免疫抑制的需要，并防止了慢性排斥反应的发展。骨髓移植确实有局限性。具体而言，这些局限性包括与致死性调节、移植物抗宿主病和植入失败相关的发病率。目前与致死性条件反射相关的发病率和死亡率不能证明I型糖尿病耐受诱导或自身免疫状态中断是合理的。目前研究的目标是确定受体和供体中优化植入以逆转与BMT相关的风险/效益比的那些因素。本文就造血干细胞嵌合体对糖尿病的影响作一综述。
Type I diabetes is a systemic autoimmune disease. Evidence is accumulating that autoimmune diseases such as type I diabetes are linked to the bone marrow hematopoietic stem cell (HSC) itself rather than its derivatives, HSC chimerism achieved through bone marrow transplantation (BMT) may affect type I diabetes in two ways: first, to induce tolerance to pancreas and islet cell transplants; and second, to reverse the autoimmune process prior to the development of terminal complications. Transplantation of bone marrow from normal donors into patients with hematologic malignancy and coexistent type I diabetes has reversed the systemic diabetic autoimmune process. Donor HSCs can also be utilized for the induction of donor-specific tolerance to islet cell transplants. Islet or whole pancreas transplantation is the most physiologic approach to treating type I diabetes, Currently, this is limited by the requirement for high-dose chronic nonspecific immunosuppression to prevent rejection. Despite these agents, chronic rejection remains the primary cause for late graft loss. Donor-specific tolerance eliminates the requirement for immunosuppression and prevents the development of chronic rejection, Bone marrow transplantation does have limitations. In particular these limitations include the morbidity associated with lethal conditioning, graft-versus-host disease, and failure of Engraftment. Currently the morbidity and mortality associated with lethal conditioning could no; be justified fo; tolerance induction or interruption of the autoimmune state in type I diabetes. The goal of current research is to identify those factors in both recipient and donor that optimize engraftment to reverse the risk/benefit ratio associated with BMT. This article reviews the state of the art for HSC chimerism affecting diabetes.