3D Bioprinted retina models for drug screening

用于药物筛选的 3D 生物打印视网膜模型

• 批准号: 10916043
• 负责人: Marc Ferrer
• 金额: $ 226.91万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10916043
• 关键词: 3-Dimensional; Blood-Retinal Barrier; Bruch' s basal membrane structure; Choroid; Choroidal Neovascularization; Disease; Drug Modelings; Drug Screening; Engineering; Extracellular Matrix; Goals; Human; Pathologic Neovascularization; Photoreceptors; Prevention; Recovery; Recurrence; Retina; Retinal Diseases; Structure of retinal pigment epithelium; Techniques; Therapeutic; Tissue Model; Tissues; Vascular Endothelium; Vascularization; Virus Diseases; Vision; ZIKV infection; angiogenesis; bevacizumab; bioprinting; clinically relevant; hypoxia inducible factor 1; improved; in vitro Model; induced pluripotent stem cell; new therapeutic target; therapeutic development; therapeutic target

An engineered ocular tissue of outer blood retina barrier containing RPE and three dimensional (3D) vascularized tissue has been produced using bioprinting techniques with human induced pluripotent stem cells. It successfully recapitulates features of choriocapillaris and components of Bruchs membranes including RPE induced vascular endothelial fenestration and extracellular matrix formation. We have further demonstrated that HIF-1 induced angiogenesis towards RPE in the tissue and the reduction of the induced angiogenesis with improved barrier functions by bevacizumab treatment. We have also explored the usefulness of this 3D retina tissue model to investigate Zika virus infection and demonstrated viral infection in the tissue and disruption of barrier function. This 3D vascularized ocular tissue model therefore provides extensive opportunities to study underlying mechanisms of relevant diseases and the development of therapeutics.

利用生物打印技术，利用人诱导多能干细胞制备了含RPE和三维血管化组织的体外血视网膜屏障眼组织。它成功地概括了绒毛膜的特征和布鲁氏膜的成分，包括RPE诱导的血管内皮开窗和细胞外基质的形成。我们进一步证明了HIF-1诱导了组织中RPE的血管生成，贝伐单抗治疗减少了诱导的血管生成，改善了屏障功能。我们还探索了这种3D视网膜组织模型在研究寨卡病毒感染方面的有用性，并证明了病毒在组织中的感染和屏障功能的破坏。因此，这种三维血管化眼组织模型为研究相关疾病的潜在机制和治疗方法的发展提供了广泛的机会。

项目成果

A platform of assays for the discovery of anti-Zika small-molecules with activity in a 3D-bioprinted outer-blood-retina model.

• DOI: 10.1371/journal.pone.0261821
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Dorjsuren D;Eastman RT;Song MJ;Yasgar A;Chen Y;Bharti K;Zakharov AV;Jadhav A;Ferrer M;Shi PY;Simeonov A
• 通讯作者: Simeonov A