Hasse C, Klöck G, Zielke A, Schlosser A, Barth P, Zimmermann U, Rothmund M
Department of Surgery, Philipps-University of Marburg, Marburg, Germany.
Int J Artif Organs. 1996 Dec;19(12):735-41.
Microencapsulation of tissues is an alternative to postoperative immunosuppression in transplantation. In 1994 iso-, allo- and xenotransplantation of microencapsulated parathyroid tissue was achieved in vivo. However, continued analysis of the coating substance (an alginate) determined mitogenic properties. Here, we report on the in vitro and in vivo function of parathyroid tissue microencapsulated with a novel amitogenic alginate suitable for use in humans. To assess in vitro function, parathyroid tissue encapsulated with mitogenic and amitogenic alginate was exposed to rising concentrations of calcium. For in vivo experiments, it was isotransplanted into parathyroidectomized rats. PTH release into medium and PTH serum levels as well as calcium levels of recipient rats were analyzed and compared to native (non-microencapsulated) tissue and empty capsules, respectively. In vivo, transplants were excised and subjected to histologic examination six months after trans-plantation. In vitro, parathyroid tissue encapsulated with amitogenic alginate releases approximately half of the PTH of the native tissue, not different from tissue encapsulated with the mitogenic alginate. In vivo, the novel alginate preserved parathyroid function similar to that of native tissue over the six month period resulting in complete reversal of hypoparathyroidism. Correspondingly, histologic examination revealed vital parathyroid tissue in intact microcapsules. By establishing in vitro function and successful long-term transplantation, we have documented the principle of microencapsulation of parathyroid tissue to be effective also with the novel amitogenic alginate, which is suitable for clinical use.
组织微囊化是移植术后免疫抑制的一种替代方法。1994年,微囊化甲状旁腺组织的同基因、异基因和异种移植在体内获得成功。然而,对包被物质(一种藻酸盐)的持续分析确定了其促有丝分裂特性。在此,我们报告用一种适用于人类的新型无促有丝分裂藻酸盐微囊化的甲状旁腺组织的体外和体内功能。为评估体外功能,将用促有丝分裂和无促有丝分裂藻酸盐包囊的甲状旁腺组织暴露于不断升高的钙浓度下。对于体内实验,将其同基因移植到甲状旁腺切除的大鼠体内。分析并比较了移植受体大鼠的甲状旁腺激素(PTH)释放到培养基中的情况、血清PTH水平以及钙水平,分别与天然(未微囊化)组织和空胶囊进行比较。在体内,移植六个月后切除移植物并进行组织学检查。在体外,用无促有丝分裂藻酸盐包囊的甲状旁腺组织释放的PTH约为天然组织的一半,与用促有丝分裂藻酸盐包囊的组织无差异。在体内,新型藻酸盐在六个月期间维持了与天然组织相似的甲状旁腺功能,导致甲状旁腺功能减退完全逆转。相应地,组织学检查显示完整微胶囊内有存活的甲状旁腺组织。通过确立体外功能和成功的长期移植,我们证明了甲状旁腺组织微囊化的原理对于这种适用于临床的新型无促有丝分裂藻酸盐也是有效的。