院士講座系列１－３

講者：阮長耿院士，醫藥衛生學部
講題：血液學－血栓與止血的研究進展

摘要：「血栓與止血」是血液學的一個重要研究方向。止血機制異常會導致出血與血栓性疾病。血栓性疾病(心肌梗死,腦梗塞、肺栓塞等) 嚴重危害人類健康。

出血性疾病分為以下幾類：（1）血管壁功能異常；（2）血小板異常(血小板減少與血小板功能異常)；（3）凝血功能異常（4）纖維蛋白溶解亢進；（5）DIC、迴圈抗凝物質增多等因素導致的出血。近年來免疫性血小板減少症（ITP）的基礎和臨床研究取得很大的進展。

血栓性疾病包括動脈血栓和靜脈血栓，比出血性疾病更為常見。動脈血栓是血管未破時動脈粥樣斑塊脫落而造成血管內皮下膠原暴露、血小板活化，形成血小板血栓，臨床上可致心梗、腦梗等心腦血管事件。靜脈血栓是由於先天性或獲得性原因，導致體內凝血因數活性過高，抗凝蛋白活性下降，而在血管內形成纖維蛋白凝塊。它與臨床各科都有關係，包括婦產科、骨科、腫瘤科等。

展望血栓與出血性疾病的未來研究方向，主要的課題將包括：血液系統與血管系統的相互作用及其對血栓的影響、血小板膜糖蛋白信號傳導機制的深入研究、ITP發病機制的深入研究、安全有效的凝血因數替代物和新一代抗栓藥物的研發等。這些課題所涉及的研究領域已經不局限於血液學本身，而是廣泛地與幹細胞生物學、免疫學、生物化學相聯繫，也需要臨床多學科的密切合作。

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講者：程京院士，醫藥衛生學部
講題：個性化診斷平台技術開發

摘要：Individualized diagnosis is critical for appropriate therapies based on the patient’s genetic background. Genechips and high throughput sequencing are both powerful tools for individualized diagnosis. CapitalBio Corporation has invented series of genetic testing products. To prevent birth defects, CapitalBio has developed a cytogenomic microarray for the detection of chromosomal abnormalities,a sequencing based genetic testing of 287 pediatric Mendelian disorders, and a deafness gene mutation detection array. For infectious diseases, CapitalBio has developed multiple microfluidic chips for the detection of respiratory pathogens, tuberculosis, hepatitis related viruses and their drug resistance, which help doctors to make medical decisions. For a variety of tumors, circulating microRNA detection platforms were developed for the early prediction and detection of cancers. Detection for cancers by combined microRNA and protein biomarkers has significantly increased the detection sensitivity of clinical samples involving patients with liver cancer, lung cancer, stomach cancer and cervical cancer. Individualized diagnosis also involves traditional Chinese Medicine. An imaging-based eye white analysis system was developed which consists of a digital imaging device capable of capturing eye images and an image processing system which enables the recognition, extraction and analysis of the images.

講者：夏照帆院士，醫藥衛生學部
講題：Wound Repair Strategies by Inducing Endogenous Stem Cells

摘要：Stem cells are the foundation of early embryonic development and organogenesis and contribute to the renewal and regeneration of adult tissue. Therefore, stem cell-based therapy has been one of the best documented approaches in regenerative medicine, promising cures for a multitude of diseases and disorders, including skin wound repair.

The traditional strategy for stem cell-based therapy is autologous stem cell transplantation. Cells are harvested and isolated firstly and identified as stem cell subsequently. The cells are expected to home to the site of interest or stay at the site of injection, depending on the particular application. However, the stem cell transplantation strategy has many limitations in the clinical application, such as long period of amplification in vitro, possible contamination during culture, uncertain inducing conditions, uncertain intake rate, loss control of cells fate after transplantation and potential of malignant transformation. As a result, the clinical translation and application of the traditional strategy for stem cell-based therapy are greatly restricted. Recently, many studies have demonstrated that the endogenous stem cells either from the around injured skin or from the distant site like bone marrow can be attracted to the wound and involve the repairing and regeneration of the skin under certain conditions, which may indicate a new therapeutic option for in situ wound repair and skin regeneration by capturing endogenous stem cell. Therefore, skin wound repairing method by mobilization, chemotaxis and capturing endogenous stem cells to stimulate the body self-repairing and reconstruction may offer new insights into in vivo tissue engineering and hold great promise for the future of clinical translation.

We applied full-thickness skin excisional wounds mouse model and used G-CSF as a starter of stem cell mobilization. The results showed that mobilisation of stem cells by G-CSF can significantly increase the amount of stem cells at injury site, which in turn accelerates wound healing after skin injury. In another research, we overexpressed SDF-1α, a biochemical signal which can chemotaxis endogenous stem cells to the injury sites, in human dermal fibroblasts (HDF). Complexes constructed by amniotic membrane microparticles (mAM) and HDF or SDF-1αovHDF were developed. Transplantation of complexes onto full-thickness skin defects mice demonstrated that overexpression of SDF-1α could chemotaxize endothelial progenitor cells (EPCs) to reach local wounds and captured them, thus further accelerating angiogenesis in the transplant site. In order to further optimize chemotaxis and capture function of SDF-1 in promoting wound healing, nanoparticles fabricated by PPADT polymers was synthesized and SDF-1α was encapsulated in the nanoparticles. SDF-1α-PPADT nanoparticles are relatively stable under normal physiological conditions, whereas sensitive to the high levels of ROS in wounded areas, which enabled the targeted release of SDF-1α in wounds and surrounding tissues. In mice with full-thickness skin defects, SDF-1α was effectively released and targeted to the wounds, thus promoting the chemotaxis of bone marrow mesenchymal stem cells toward the wound.

Our studies give a brief outlook on the improvement of mobilization, chemotaxis and capturing of endogenous stem cells through different manners, which may prove to be a new strategy to accelerate wound healing. Further work on optimizing the biomaterials and understanding the mechanisms in accelerating wound healing and the long-term outcomes of healed wounds will be critical for introduction of these findings into clinical practice.

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院士講座系列４

講者：馬遠良院士，信息與電子工程學部
講題：海洋的協同觀測與信息獲取

摘要：
當前海空天信息聯網止於海面。對於約佔地球表面積71%的海面之下，觀測和信息獲取存在極大的困難。光波、電磁波在海水中的傳播不如聲波，因此聲波是當今對海觀測和信息獲取的主要手段。聲波受氣象水文三維分佈及地理環境的影響很大，氣象水文的變化主要是由於海流和海面的氣液熱交換所產生的，應該可以用空天遙感和海洋動力學模型來預測。聲學觀測還存在傳播速度慢、空時分辨力不高、可用頻帶窄傳輸速率低等缺陷。因此利用各種物理場與聲場協同觀測、各取所長，是必然的選擇。本報告將陳述以上各種問題的當前面貌，說明其原因，探討未來的發展方向。