微納醫學與組織工程

杜亞楠

清華大學醫學院教授

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?微組織工程助力再生治療和病理研究

实验室主页 http://dulab-tsinghua.net/ ?杜亞楠教授2002年本科结业于清华大学化学工程系;2007年博士结业于新加坡国立大学生物工程系;2007至2010年于美国麻省理工学院和哈佛医学院进行博士後研究。杜亞楠教授在“微组织工程”这一特色交织研究偏向进行创新探索,实现理论探究和技术转化。开发的3D微组织技术可作为新一代细胞药物的扩增制备平台和药剂学递送系统革新体外细胞培养和再生医学;同时可辅助建设仿生生理/病理模型,用于高通量药物筛选和病理机制研究。发表多篇高影响力论文,相关微组织工程产物已经商品化,并获得美国FDA和中国药监局相关资质。为再生医学、药物开发和病理研究提供新型平台技术、理论模型息争决方案。

在“微組織工程”特色交织研究偏向實現理論研究的突破和技術轉化的落地

杜亞楠教授在 “微组织工程”领域研究内容为应用微纳加工技术结合生物质料工程、生物力学、基因编辑等手段构建“精准化”和“规模化”3D微尺度再生和病理微情况,为再生医学研究提供创新理论基础息争决方案。重点关注种种干细胞微情况,免疫细胞微情况和纤维化等病理微情况的构建、微情况内细胞-细胞,细胞-基质互作机制研究以及相关的再生医学应用转化。其中,基于干细胞3D微组织提出和实现了“细胞药剂学”理念和应用,实现了细胞规模化、高质量体外扩增和微创、定点、高效体内递送和再生治疗,以解决现有干细胞再生疗法中细胞来源数量不足和质量不稳定的问题,以及体内定位差、存活率低、疗效有限等问题;同时建设了“病理3D纤维化微组织阵列”技术通过构建仿生纤维化病理微组织实现了高通量抗纤维化药物筛选和潜在临床精准用药指导,并启发发现了组织纤维化发生和生长历程中“血管化和纤维化互作关系”以及“旁张力”信号介导的新型病理机制,为组织修复再生提供新思路和疗法。微组织工程焦点技术已乐成通过知识产权转让从清华大学转化进行下游的干细胞3D微组织大规模制造和药剂辅助的干细胞微组织再生治疗临床转化。其焦点产物细胞用明胶3D微载片于2020年和2021年划分获得中国药监局药品评审中心和美国FDA首款细胞药用辅料资质审批。作为全球首款可用于细胞药物开发和应用的药用级微载体辅料,预期将加速微组织工程技术在细胞和再生医学领域的转化应用。

2019-presentProfessor, School of Medicine, Tsinghua University

2018-presentPrincipal Investigator, Tsinghua-PKU, Center of Life Science

2017-2019Tenured Associate professor, School of Medicine, Tsinghua University

2014-2017Tenure-track Associate professor, School of Medicine, Tsinghua University

2010-2014Principal Investigator, School of Medicine, Tsinghua University

2007-2010Postdoctoral Fellow, Harvard-MIT Division of Health Science and Technology, MIT; Harvard Medical School, Harvard University, USA

2003-2007Ph.D. in Bioengineering, National University of Singapore, Singapore

1998-2002B.Eng. in Chemical Engineering, Tsinghua University, Beijing, China

We have been innovating in the field of ‘Microtissue Engineering’, with accomplishment in the theoretical elucidation and technological translation. Microtissue Engineering integrates biomaterials, microfabrication, biophysical and gene editing technologies to engineer and fine-tune the microscale 3D cell or tissue microenvironments, whichprovides innovative and effective tools and solutions for regenerative medicine, drug discovery and pathology study. We focus on1)establishment of stem cell microenvironment, immune cell microenvironment as well as fibrosis pathological microenvironments; 2)the mechanism investigation of cell-cell, cell-matrix interactions and3)their translational applications in regenerative medicine.

Specifically, through theconstruction of 3D stem cell micro-tissue, large-scale/high-quality in vitro stemcell manufacture and minimally invasive, targeted, efficient in vivo delivery andregeneration treatment have been accomplished; meanwhile, the 3D pathological micro-tissuearray technology realized high-throughput and accurate anti-fibrosis drugscreening and evaluation. The new pathological mechanism of cell mechanicalcommunication based on 'paratensile signaling' in the development of tissuefibrosis was discovered. 2patents of micro-tissue engineering have been commercially translated with relatedproducts approved as the first cell pharmaceutical excipients by both China CDE and US FDA.

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Lab web:http://dulab-tsinghua.net/

1.Exendin-4 Gene-modification and Microscaffold Encapsulation Promote Self-persistence and Anti-diabetic Activity of MSCs,Science Advances, 2021, DOI: 10.1126/sciadv.abi4379

2.Matrix -transmitted paratensile signaling enables myofibroblast-1 fibroblast crosstalk in fibrosis expansion,PNAS, 2020, 03(27): 4-27

3.Cryoprotectant enables structural control of porous scaffolds for exploration of cellular mechano-responsiveness in 3D,Nature Communications, 2019, 10: 0-3491

4.Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis,Nature Materials, 2017, 16(12): 1252-1261

5.Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia,PNAS, 2014, 111(37): 13511-13516

學術榮譽與獎勵

2021 国家自然科学基金“杰出青年”项目获得者

2018 北京自然科学基金“杰出青年”项目获得者

2017 教育部青年长江学者奖励计划

2015 国家自然科学基金“优秀青年”项目获得者

2014 清华大学“學術新人