探討人工胰島建構之要素: 血管與自主神經網絡

Abstract

近年來，為了因應病人的難症與絕症，許多新創醫療應運而生，再生醫學為利用細胞或幹細胞技術進行移植治療，以修補或取代受損組織。由於牙髓幹細胞具有高分化能力及於成年人較易取得的雙重優勢，所以過去研究曾使用牙髓幹細胞分化出可移植到糖尿病人身上並且分泌胰島素的胰島細胞聚集體。不過，若要能讓人工胰島能因應糖尿病病人的生理狀況調控血糖，必須有血管與神經的參與，所以若能了解完整的神經架構，可以幫助再生胰島的架構建構，使移植入糖尿病的人工胰島能因應病人生理狀況調控血糖。神經如何調控血糖的恆定,主要是透過自律神經去調控，血糖上升時，副交感神經會釋放乙烯膽鹼促進Beta細胞製造胰島素降低血糖，來達到調節體內血糖的目標。過去研究主要把胰島依照血管或鄰近臟器分區，而本篇研究承先前實驗發現胰島有分布在主要血管周邊的Insulo-venous胰島，以及單獨分布在腺泡小葉當中的Insulo-acinar 胰島。為了瞭解兩者不同與可能對胰島素分泌的貢獻與主要功能。並主要以不進行切片行為來破壞其結構，保留最完整的功能性結構。將富含胰島部分分離，進行胰島與神經血與副交感神經血管免疫螢光染色了解其具體結構並推測其功能與內部模式，實驗發現 Insulo-venous系統之胰島其內部血管分布與主要血管較接近，且結構與模型均較為密集，且Insulo-acinar神經為pole to pole模式，實現單向神經控制胰島素的分泌，而 Insulo-venous神經模式是center to periphery模式，可以組織和綜合複雜神經訊息幫助胰島素分泌，對於Insulo-venous與Insulo-acinar的神經血管網絡的理解希望對未來人工胰島結構的確立以及血糖調控功能的協作有所幫助。

In recent years, in response to challenging and incurable diseases, many innovative medical approaches have emerged. Regenerative medicine, which uses cell or stem cell technology for transplantation therapy, aims to repair or replace damaged tissues. Due to the dual advantages of dental pulp stem cells, including their high differentiation potential and ease of accessibility in adults, past studies have used them to differentiate into islet cell aggregates that can be transplanted into diabetic patients and secrete insulin. However, to enable artificial islets to regulate blood glucose in response to the physiological conditions of diabetic patients, the participation of blood vessels and nerves is necessary. Understanding the complete neural architecture can aid in constructing the structure of regenerative islets, allowing transplanted artificial islets to regulate blood glucose in response to the patient's physiological state.The autonomic nervous system primarily regulates blood glucose homeostasis. When blood glucose levels rise, the parasympathetic nervous system releases acetylcholine to stimulate beta cells to produce insulin, thereby lowering blood glucose and achieving regulation. Past research mainly categorized islets based on blood vessels or nearby organs. This study builds on previous experiments that discovered the distribution of Insulo-venous islets around major blood vessels and Insulo-acinar islets isolated within acinar lobules. To understand the differences between these two types of islets, their potential contributions to insulin secretion, and their primary functions, we aimed to preserve the most intact functional structures without slicing or damaging them. We used immunofluorescence staining for islets, neurovasculature, and parasympathetic innervation to understand their specific structures and infer their functions and internal patterns.The experiment found that the internal vascular distribution of Insulo-venous islets is closer to major blood vessels, with a denser structure and model. The Insulo-acinar neural pattern follows a pole-to-pole model, achieving unidirectional neural control of insulin secretion. In contrast, the Insulo-venous neural pattern follows a center-to-periphery model, capable of organizing and integrating complex neural signals to aid insulin secretion. Understanding the neurovascular networks of Insulo-venous and Insulo-acinar islets is hoped to assist in establishing the structure of artificial islets and the collaborative regulation of blood glucose in the future.