The Effect of Tissue Preparation and Donor Age on Striatal Graft Morphology in the Mouse.
The Effect of Tissue Preparation and Donor Age on Striatal Graft Morphology in the Mouse.
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DOI：
10.1177/0963689717744788
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发表时间：
2018-03
影响因子：
3.3
通讯作者：
Rosser AE
中科院分区：
文献类型：
--
作者：
Harrison DJ;Roberton VH;Vinh NN;Brooks SP;Dunnett SB;Rosser AE
亨廷顿病(HD)是一种进行性神经退行性疾病，纹状体中棘神经元(MSN)丢失。神经元替代疗法旨在通过纹状体移植供体MSN前体细胞来替代MSN，成功地改善了大鼠HD模型中的HD样缺陷，并改善了患者的功能。与同等的大鼠移植物相比，HD小鼠模型中的移植细胞更具变异性，细胞存活率更低，但转基因HD模型中的大多数是小鼠。提高小鼠移植的质量和一致性将打开获得这种更广泛的啮齿动物模型的途径，并促进研究以增加对移植机制的了解，这对于将移植作为HD的治疗方法是必不可少的。在此，我们确定了供体年龄、细胞准备和供体/宿主菌株的选择如何影响喹啉酸损伤的HD小鼠模型的初级胚胎移植物的质量。采用品系内(W-S)和品系间(B-S)供体/宿主范式，比较了来自胚胎12天和14天小鼠的供体组织作为游离悬液和最小处理组织块(TP)的移植。移植物存活率良好，尽管移植物体积和细胞成分变化很大。细胞制备对移植物的影响因供者年龄的不同而有显著差异，与TP相比，E14细胞悬液产生更大的移植物。相反，从E12供体组织中提取的TP效果更好。W-S模型产生的移植物体积更大，msn含量更高，虽然在所有组中都观察到了高水平的激活的小胶质细胞，但在B-S模型中发现了更多的小胶质细胞。综上所述，我们表明组织准备对移植物形态的影响取决于所使用的供体组织的年龄。小胶质细胞的激活在所有组中的存在突出了宿主免疫反应作为小鼠移植的一个重要考虑因素。
Huntington's disease (HD) is a progressive neurodegenerative disease in which striatal medium spiny neurons (MSNs) are lost. Neuronal replacement therapies aim to replace MSNs through striatal transplantation of donor MSN progenitors, which successfully improve HD-like deficits in rat HD models and have provided functional improvement in patients. Transplants in mouse models of HD are more variable and have lower cell survival than equivalent rat grafts, yet mice constitute the majority of transgenic HD models. Improving the quality and consistency of mouse transplants would open up access to this wider range of rodent models and facilitate research to increase understanding of graft mechanisms, which is essential to progress transplantation as a therapy for HD. Here we determined how donor age, cell preparation, and donor/host strain choice influenced the quality of primary embryonic grafts in quinolinic acid lesion mouse models of HD. Both a within-strain (W-S) and a between-strain (B-S) donor/host paradigm were used to compare transplants of donor tissues derived from mice at embryonic day E12 and E14 prepared either as dissociated suspensions or as minimally manipulated tissue pieces (TP). Good graft survival was observed, although graft volume and cellular composition were highly variable. The effect of cell preparation on grafts differed significantly depending on donor age, with E14 cell suspensions yielding larger grafts compared to TP. Conversely, TP were more effective when derived from E12 donor tissue. A W-S model produced larger grafts with greater MSN content, and while high levels of activated microglia were observed across all groups, a greater number was found in B-S transplants. In summary, we show that the effect of tissue preparation on graft morphology is contingent on the age of donor tissue used. The presence of microglial activation in all groups highlights the host immune response as an important consideration in mouse transplantation.
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影响因子：
3.7
作者：
Chen ZF;Matsumura K;Wang H;Arellano SM;Yan X;Alam I;Archer JA;Bajic VB;Qian PY
通讯作者：
Qian PY
DOI：
10.1073/pnas.82.24.8780
发表时间：
1985-12-01
影响因子：
11.1
作者：
GERFEN, CR;BAIMBRIDGE, KG;MILLER, JJ
通讯作者：
MILLER, JJ
影响因子：
34.7
作者：
Brown, Guy C.;Neher, Jonas J.
通讯作者：
Neher, Jonas J.
影响因子：
3.3
作者：
FREEMAN, TB;SANBERG, PR;KORDOWER, JH
通讯作者：
KORDOWER, JH
影响因子：
3.3
作者：
Fricker, RA;Torres, EM;Dunnett, SB
通讯作者：
Dunnett, SB