Bioengineering tissue morphogenesis and function in human neural organoids.
Bioengineering tissue morphogenesis and function in human neural organoids.
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DOI：
10.1016/j.semcdb.2020.05.025
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发表时间：
2021-03
影响因子：
7.3
通讯作者：
Ashton RS
中科院分区：
文献类型：
--
作者：
Fedorchak NJ;Iyer N;Ashton RS
在过去的十年中，科学家们已经开始使用人类多能干细胞（hPSC）衍生的类器官在体外模拟CNS发育，功能和疾病。使用传统方案，这些3D组织是通过将分化hPSC聚集体的先天涌现特性与诱导氧气和营养物质间质转运的生物反应器环境以及可选的支持性水凝胶细胞外基质（ECM）相结合来生成的。在延长培养期间，hPSC衍生的神经类器官（hNO）获得毫米级尺寸，具有内部微观细胞结构、细胞表型和神经元回路行为，模拟在发育中的脑、眼或脊髓中观察到的那些。早期的研究评估了这些类器官的细胞结构和表型特征，并对支配CNS发育的形态发生过程提供了前所未有的见解。与人类胎儿组织的比较揭示了它们的显著相似性和差异性。虽然hNO具有当前的疾病建模应用和显著的未来前景，但它们作为解剖学和生理学模型的价值是有限的，因为它们不能可重复地形成并重现更成熟的体内特征。这些包括仿生宏观组织形态学，定位形态发生信号传导中心以协调适当的空间组织和离散组织区域的内部和相互连接，生理相关神经回路的成熟，以及可以支持持续体外组织生长的血管网络的形成。为了解决这些不足之处，科学家们已经开始将类器官培养与生物工程技术和方法相结合，包括基因组编辑，生物材料以及微制造和微流体平台，这些平台能够时空控制细胞分化或协调类器官形态发生的生化和生物物理线索。这篇综述将研究最近的进展hNO技术和培养策略，促进可重复的体外形态和更大的仿生结构和功能。
Over the last decade, scientists have begun to model CNS development, function, and disease in vitro using human pluripotent stem cell (hPSC)-derived organoids. Using traditional protocols, these 3D tissues are generated by combining the innate emergent properties of differentiating hPSC aggregates with a bioreactor environment that induces interstitial transport of oxygen and nutrients and an optional supportive hydrogel extracellular matrix (ECM). During extended culture, the hPSC-derived neural organoids (hNOs) obtain millimeter scale sizes with internal microscale cytoarchitectures, cellular phenotypes, and neuronal circuit behaviors mimetic of those observed in the developing brain, eye, or spinal cord. Early studies evaluated the cytoarchitectural and phenotypical character of these organoids and provided unprecedented insight into the morphogenetic processes that govern CNS development. Comparisons to human fetal tissues revealed their significant similarities and differences. While hNOs have current disease modeling applications and significant future promise, their value as anatomical and physiological models is limited because they fail to form reproducibly and recapitulate more mature in vivo features. These include biomimetic macroscale tissue morphology, positioning of morphogen signaling centers to orchestrate appropriate spatial organization and intra- and inter-connectivity of discrete tissue regions, maturation of physiologically relevant neural circuits, and formation of vascular networks that can support sustained in vitro tissue growth. To address these inadequacies scientists have begun to integrate organoid culture with bioengineering techniques and methodologies including genome editing, biomaterials, and microfabricated and microfluidic platforms that enable spatiotemporal control of cellular differentiation or the biochemical and biophysical cues that orchestrate organoid morphogenesis. This review will examine recent advances in hNO technologies and culture strategies that promote reproducible in vitro morphogenesis and greater biomimicry in structure and function.
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影响因子：
13.6
作者：
Hinton TJ;Jallerat Q;Palchesko RN;Park JH;Grodzicki MS;Shue HJ;Ramadan MH;Hudson AR;Feinberg AW
通讯作者：
Feinberg AW
DOI：
10.1073/pnas.0910786107
发表时间：
2010-06-08
影响因子：
11.1
作者：
Chizhikov, Victor V.;Lindgren, Anne G.;Millen, Kathleen J.
通讯作者：
Millen, Kathleen J.
影响因子：
4.6
作者：
Duval, Nathalie;Vaslin, Celia;Ribes, Vanessa C.
通讯作者：
Ribes, Vanessa C.
影响因子：
11.8
作者：
Guo, Guoji;Huss, Mikael;Robson, Paul
通讯作者：
Robson, Paul
影响因子：
64.8
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
通讯作者：
Paşca SP