Hashemian Sanaz, O'Rourke Caitriona, Phillips James B, Strömberg Ingrid, Af Bjerkén Sara
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
Department of Life Health and Chemical Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA UK ; Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, 256 Gray's Inn Road, London, WC1X 8LD UK.
Springerplus. 2015 Sep 28;4:558. doi: 10.1186/s40064-015-1362-3. eCollection 2015.
One obstacle with grafting of dopamine neurons in Parkinson's disease is the insufficient ability of the transplant to reinnervate the host striatum. Another issue is the prospective interaction between the donor fetal tissue and the adult astrocytes of the host. To study nerve fiber growth and its interaction with immature/mature astrocytes, ventral mesencephalic (VM) organotypic rat tissue cultures from embryonic days (E) 12, E14, and E18 were studied up to 35 days in vitro (DIV), and co-cultures of E14 VM tissue and mature green fluorescent protein (GFP)-positive astrocytes were performed. Generally, nerve fibers grew from the tissue slice either in association with a monolayer of migrated astroglia surrounding the tissue (glial-associated), or distal to the astroglia as non-glial-associated outgrowth. The tyrosine hydroxylase (TH)-positive glial-associated nerve fiber outgrowth reached a plateau at 21 DIV in E12 and E14 cultures. In E18 cultures, TH-positive neurons displayed short processes and migrated onto the astrocytes. While the non-glial-associated nerve fiber outgrowth dominated the E14 cultures, it was found absent in E18 cultures. The GFP-positive cells in the VM and GFP-positive astrocyte co-cultures were generally located distal to the monolayer of migrated fetal astrocytes, a few GFP-positive cells were however observed within the astrocytic monolayer. In those cases TH-positive neurons migrated towards the GFP-positive cells. Both the non-glial- and glial-associated nerve fibers grew onto the GFP-positive cells. Taken together, the glial-associated growth has limited outgrowth compared to the non-glial-associated nerve fibers, while none of the outgrowth types were hampered by the mature astrocytes.
帕金森病中多巴胺神经元移植的一个障碍是移植体重新支配宿主纹状体的能力不足。另一个问题是供体胎儿组织与宿主成年星形胶质细胞之间可能存在的相互作用。为了研究神经纤维生长及其与未成熟/成熟星形胶质细胞的相互作用，对胚胎第12天（E12）、E14和E18的腹侧中脑（VM）器官型大鼠组织培养物进行了长达体外35天（DIV）的研究，并进行了E14 VM组织与成熟绿色荧光蛋白（GFP）阳性星形胶质细胞的共培养。一般来说，神经纤维从组织切片中生长出来，要么与围绕组织迁移的星形胶质细胞单层相关（胶质细胞相关），要么在星形胶质细胞远端以非胶质细胞相关的方式生长。酪氨酸羟化酶（TH）阳性的胶质细胞相关神经纤维生长在E12和E14培养物中于21 DIV达到平台期。在E18培养物中，TH阳性神经元显示出短突起并迁移到星形胶质细胞上。虽然非胶质细胞相关神经纤维生长在E14培养物中占主导，但在E18培养物中未发现。VM和GFP阳性星形胶质细胞共培养物中的GFP阳性细胞通常位于迁移的胎儿星形胶质细胞单层的远端，但在星形胶质细胞单层内也观察到一些GFP阳性细胞。在这些情况下，TH阳性神经元向GFP阳性细胞迁移。非胶质细胞相关和胶质细胞相关的神经纤维都生长到GFP阳性细胞上。综上所述，与非胶质细胞相关神经纤维相比，胶质细胞相关生长的生长受限，而成熟星形胶质细胞并未阻碍任何一种生长类型。
