Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine.
Coculture techniques for modeling retinal development and disease, and enabling regenerative medicine.
复制标题
DOI：
10.1002/sctm.20-0201
复制
发表时间：
2020-12
影响因子：
6
通讯作者：
Steel DH
中科院分区：
文献类型：
--
作者：
Ghareeb AE;Lako M;Steel DH
干细胞衍生的视网膜类器官提供了通过研究体外模型或生成用于移植的组织来治愈广泛病因的视网膜变性的机会。然而，尽管在动物和一些人类试点研究中做了大量工作，但尚未开发出令人满意的疗法。视网膜再生医学的两个主要挑战是：（a）对移植功能至关重要的物理细胞-细胞相互作用没有形成，以及（B）宿主环境没有提供合适的发育队列。有几种策略可以改善细胞移植的递送、整合、成熟和功能。这些包括微创递送、生物相容性材料载体、视网膜细胞片和光遗传学。优化动物模型中的几个变量实际上是困难的，受到解剖学和疾病病理学的限制，这些病理学通常与人类不同，并且面临监管和伦理挑战。需要高通量方法来实验优化这些变量。视网膜类器官对于这些模型的成功至关重要。在目前的状态下，它们不包含代表性的视网膜色素上皮（RPE）-感光细胞界面，也不包含血管成分，其直接影响神经视网膜表型，并且已知在常见的视网膜疾病如年龄相关性黄斑变性中功能障碍。先进的共培养技术模拟了RPE-感光细胞和RPE-布鲁赫-脉络膜毛细血管的相互作用，可以结合疾病特异性的人类视网膜类器官并克服这些缺点。在此，我们回顾视网膜共培养模型的神经视网膜，视网膜色素上皮细胞，和choriocapillaris。我们描述了在视网膜器官发生、疾病建模和视网膜变性再生细胞疗法优化的研究中对这种系统的科学需求。神经视网膜、视网膜色素上皮和脉络膜毛细血管高度相互依赖，因此需要共培养技术来了解正常发育和疾病。此外，共培养技术将使再生疗法的优化和可移植的多组织片的发展成为可能。
Stem cell‐derived retinal organoids offer the opportunity to cure retinal degeneration of wide‐ranging etiology either through the study of in vitro models or the generation of tissue for transplantation. However, despite much work in animals and several human pilot studies, satisfactory therapies have not been developed. Two major challenges for retinal regenerative medicine are (a) physical cell‐cell interactions, which are critical to graft function, are not formed and (b) the host environment does not provide suitable queues for development. Several strategies offer to improve the delivery, integration, maturation, and functionality of cell transplantation. These include minimally invasive delivery, biocompatible material vehicles, retinal cell sheets, and optogenetics. Optimizing several variables in animal models is practically difficult, limited by anatomical and disease pathology which is often different to humans, and faces regulatory and ethical challenges. High‐throughput methods are needed to experimentally optimize these variables. Retinal organoids will be important to the success of these models. In their current state, they do not incorporate a representative retinal pigment epithelium (RPE)‐photoreceptor interface nor vascular elements, which influence the neural retina phenotype directly and are known to be dysfunctional in common retinal diseases such as age‐related macular degeneration. Advanced coculture techniques, which emulate the RPE‐photoreceptor and RPE‐Bruch's‐choriocapillaris interactions, can incorporate disease‐specific, human retinal organoids and overcome these drawbacks. Herein, we review retinal coculture models of the neural retina, RPE, and choriocapillaris. We delineate the scientific need for such systems in the study of retinal organogenesis, disease modeling, and the optimization of regenerative cell therapies for retinal degeneration. Neural retina, retinal pigment epithelium, and choriocapillaris are highly interdependent and therefore coculture techniques are required to understand normal development and disease. Furthermore, coculture techniques will enable the optimization of regenerative therapies and the development of transplantable multitissue sheets.
登录
查看更多内容
影响因子：
2.4
作者：
Boochoon, Kieran S.;Manarang, Joseph C.;Davis, Joshua T.;McDermott, Alison M.;Foster, William J.
通讯作者：
Foster, William J.
DOI：
10.3791/57084
发表时间：
2018-04-12
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Cai H;Gong J;Del Priore LV;Tezel TH;Fields MA
通讯作者：
Fields MA
影响因子：
5.9
作者：
Assawachananont, Juthaporn;Mandai, Michiko;Okamoto, Satoshi;Yamada, Chikako;Eiraku, Mototsugu;Yonemura, Shigenobu;Sasai, Yoshiki;Takahashi, Masayo
通讯作者：
Takahashi, Masayo
影响因子：
12.4
作者：
Barnea-Cramer, Alona O.;Singh, Mandeep;MacLaren, Robert E.
通讯作者：
MacLaren, Robert E.
影响因子：
9.7
作者：
Chirco KR;Worthington KS;Flamme-Wiese MJ;Riker MJ;Andrade JD;Ueberheide BM;Stone EM;Tucker BA;Mullins RF
通讯作者：
Mullins RF