矽膠和生物活性玻璃對神經幹細胞和神經前驅細胞的影響

Abstract

大部分神經退化性疾病源自於神經元死亡。為了解決神經元減少的問題，有研究指出神經幹細胞移植可以回復神經元的數量，但細胞在移植時會被打散並破壞型態，移植後的存活和神經元分化也較差。由於矽膠具有生物相容性且能做為立體支架的材料，生物活性玻璃也被發現對多種細胞有助益，因此我們進一步測試它們在神經幹細胞培養上的效果。先使用P19小鼠胚胎瘤细胞株作為研究幹細胞的模型，發現聚二甲基矽氧烷矽膠和生物活性玻璃58S具有生物相容性，不會影響P19細胞的存活、增生和神經元分化。加了氧化鋯的58S則可以增加P19細胞和其產生的神經元數量。取出出生後第七天小鼠側腦室的細胞，進行懸浮培養來純化神經幹細胞並進行實驗。發現聚二甲基矽氧烷同樣具有生物相容性，讓它有潛力成為立體支架的製作材料。加了氧化鋯的58S則可以透過抑制凋亡，增加神經幹細胞、神經前驅細胞和其所產生神經元的數量。聚二甲基矽氧烷和參雜氧化鋯的58S可能有助於解決幹細胞移植中，細胞型態被破壞和存活太差的問題，來提升治療神經退化性疾病的效率。Most neurodegenerative diseases are caused by a gradual loss of neurons. Previous studies have shown that neural stem cell (NSC) transplantation can restore neuron loss. However, cellular morphology is disrupted during transplantation, and transplanted NSCs exhibit poor viability and limited neuronal differentiation. Since silicone (SIL) is biocompatible and has potential as a three-dimensional (3D) scaffold material, and bioactive glass (BG) has been reported to have beneficial effects on various cell types, we aimed to examine their effects on NSCs. Using murine embryonic carcinoma cell line P19 cell as a model for stem cell research, we observed that polydimethylsiloxane (PDMS), a type of SIL, and BG 58S were biocompatible and did not affect survival, proliferation and neuronal differentiation in P19 cells, while Zr-doped 58S increased cell and neuron numbers. PDMS was also biocompatible in neural stem/progenitor cells (NSPCs) from lateral ventricles of postnatal mice, while Zr-doped 58S decreased apoptosis, leading to an increase in cell and neuron numbers. Biocompatibility and plasticity of PDMS make it a potential material for 3D scaffolds. Zr-doped 58S can inhibit apoptosis in NSCs and therefore produce more neurons. The advantages of PDMS and Zr-doped 58S may overcome poor cell viability and limited neuron production in stem cell transplantation and improve treatments for neurodegenerative diseases.