Royce Hynes Sara, McGregor Lynn M, Ford Rauch Millicent, Lavik Erin B
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
J Biomater Sci Polym Ed. 2007;18(8):1017-30. doi: 10.1163/156856207781494368.
Neural progenitor cells (NPCs) have shown promise in a number of models of disease and injury, but for these cells to be safe and effective, they must be directed to differentiate appropriately following transplantation. We have developed a photopolymerized hydrogel composed of macromers of poly(ethylene glycol) (PEG) bound to poly(L-lysine) (PLL) that supports NPC survival and directs differentiation. Green fluorescent protein (GFP) positive NPCs were encapsulated in these gels and demonstrated survival up to 17 days. When encapsulated in the gels at a photoinitiator concentration of 5.0 mg/ml, few NPCs (0.5 +/- 0.25%) demonstrated apoptosis. Furthermore, 55 +/- 6% of the NPCs cultured within the gels in epidermal growth factor (EGF) containing media differentiated into a mature neuronal cell type (neurofilament 200 positive) while the remainder 44 +/- 8% were undifferentiated (nestin positive). A small percentage, 1 +/- 0.4%, expressed the astrocytic marker glial acidic fibrilary protein. Photopolymerized PEG/PLL gels promote the survival and direct the differentiation of NPCs, making this system a promising delivery vehicle for NPCs in the treatment of injuries and diseases of the central nervous system.
神经祖细胞(NPCs)在许多疾病和损伤模型中已显示出应用前景,但要使这些细胞安全有效,必须在移植后引导它们进行适当分化。我们开发了一种由与聚(L-赖氨酸)(PLL)结合的聚(乙二醇)(PEG)大分子单体组成的光聚合水凝胶,它能支持NPCs的存活并引导其分化。绿色荧光蛋白(GFP)阳性的NPCs被封装在这些水凝胶中,并显示出长达17天的存活时间。当以5.0 mg/ml的光引发剂浓度封装在水凝胶中时,很少有NPCs(0.5 +/- 0.25%)发生凋亡。此外,在含有表皮生长因子(EGF)的培养基中于水凝胶内培养的NPCs中,55 +/- 6%分化为成熟的神经元细胞类型(神经丝200阳性),而其余44 +/- 8%未分化(巢蛋白阳性)。一小部分,1 +/- 0.4%,表达星形胶质细胞标志物胶质酸性纤维蛋白。光聚合的PEG/PLL水凝胶促进NPCs的存活并引导其分化,使该系统成为治疗中枢神经系统损伤和疾病的NPCs的一种有前景的递送载体。