我們希望透過幹細胞,組織工程,以及相關奈米材料技術,應用於神經損傷再生,抗老化與癌症治療上。 基於核心工具,目前我們實驗室有三個主軸研究方向。歡迎有興趣的學生加入我們的行列!
腦中風與其他神經退化性疾病,往往對病患造成難以挽回的不可逆傷害。面對這些嚴峻的醫療挑戰,傳統藥物治療的修復效果相對有限,使得醫學界急需嶄新的治療策略,來幫助病患重建受損的神經組織與功能。
為了突破現有治療的瓶頸,我們整合了多項前瞻性生醫技術,致力於開發新一代的神經修復方法。透過人類誘導多能幹細胞技術(human induced plurypotent stem cell, hiPSC),我們能將其精準誘導為高品質的神經幹細胞。在治療開發過程中,我們進一步結合了功能性生醫材料水膠,ˋ 作為神經幹細胞與衍生胞外體載體,仿效神經再生所需的神經系統微環境,藉此大幅提升細胞在體內的存活率與治療效能。同時,我們也積極投入相關神經系外泌體的應用,期望透過其作為傳遞關鍵修復訊號的載體,進一步促進神經網路的修復與再生。
我們期盼藉由建構這個全方位的神經幹細胞平台,發展出新穎的治療藥物與臨床方法。
Strokes and other neurodegenerative diseases often cause irreversible damage to patients. Because traditional medicines have limited healing effects, the medical field urgently needs new treatment strategies to help patients rebuild damaged nerve tissue and restore their functions.
To break through current treatment limitations, we are combining advanced biomedical technologies to develop a new generation of nerve repair methods. By using human induced pluripotent stem cell (hiPSC) technology, we can precisely guide these cells to become high-quality neural stem cells.
During our treatment development, we also use functional hydrogels as carriers for the neural stem cells and their exosomes. This mimics the neural niChe needed for nerve regeneration, which greatly improves cell survival rates and treatment effectiveness in the body. At the same time, we are actively focusing on the use of neural exosomes to deliver essential healing signals, further boosting the repair and regeneration of neural networks.
By building this comprehensive neural stem cell platform, we aim to advance scientific frontiers and develop novel therapeutic drugs and clinical methods.
我們針對腫瘤特異性標記,致力開發具高親和力的 hiPSC 衍生 CAR-T 與 CAR-NK 免疫細胞,並結合專一性核酸適體(Aptamer)技術。嵌合抗原受體(CAR)技術如同為免疫細胞配備了專屬的導航雷達,使其能主動追蹤並鎖定癌細胞;我們將此技術導入 T 細胞與自然殺手細胞(NK 細胞)中,讓 CAR-T 發揮強悍的毒殺能力與持久的免疫記憶,同時利用 CAR-NK 異體排斥性低、不易引發免疫風暴(CRS)的高安全性優勢。有別於傳統自體細胞療法需耗時客製、且受限於病患自身細胞品質的重重限制,結合 hiPSC 技術使我們能夠穩定培育出高品質、標準化,且具備量產潛力的「現成型」(Off-the-shelf)免疫細胞。同時,透過結合高專一性的核酸適體作為更精確的標靶指引,我們能大幅提升免疫細胞辨識並精準清除癌細胞的能力,進而將對正常組織的傷害降至最低。期盼能透過這些先進的細胞工程與精準標靶機制,克服現有療法的瓶頸,構築並發展出具突破性、普及度更高的新世代癌症免疫治療策略。
Targeting tumor-specific markers, we are dedicated to developing high-affinity, hiPSC-derived CAR-T and CAR-NK immune cells integrated with specialized aptamer technology.
Chimeric Antigen Receptor (CAR) technology acts like a built-in radar, enabling immune cells to actively track and lock onto cancer cells. By introducing this technology into T cells and Natural Killer (NK) cells, we harness the powerful tumor-killing ability and long-lasting immune memory of CAR-T cells. At the same time, we leverage the superior safety of CAR-NK cells, which carry a low risk of rejection and are much less likely to trigger cytokine release syndrome (CRS).
Unlike traditional personalized cell therapies—which are time-consuming to customize and limited by the patient's own cell quality—our integration of hiPSC technology allows us to reliably cultivate high-quality, standardized, and mass-producible "off-the-shelf" immune cells.
Furthermore, by utilizing highly specific aptamers as precise targeting guides, we significantly enhance the immune cells' ability to recognize and accurately eliminate cancer cells, keeping damage to healthy tissues to an absolute minimum.
Through these advanced cell engineering and precise targeting mechanisms, we aim to overcome the bottlenecks of current treatments and pioneer a breakthrough, widely accessible new generation of cancer immunotherapies.
在再生醫療的前沿領域,我們致力於將尖端的奈米分子工程與細胞生物學深度結合,開創突破性的治療策略。為此,我們正積極整合「DNA/RNA 摺紙技術」與「工程化外泌體」,構築新世代的生醫研發平台。
DNA/RNA 摺紙技術 (Nucleic Acid Origami) 顛覆了傳統對遺傳物質的認知。我們將 DNA 與 RNA 視為具備高度可塑性的生醫材料,透過精密的電腦計算與設計,在奈米尺度下將其精確組裝成特定功能的三維結構。這項技術使我們能夠開發出新穎的生醫元件,為精準標靶與組織修復提供全新的施力點。
同時,細胞間的訊息傳遞對於組織再生至關重要。外泌體 (Exosomes) 作為細胞分泌的奈米級囊泡,是極佳的天然傳遞載體。我們運用基因工程等先進技術,針對人類誘導多能幹細胞 (hiPSC) 衍生的幹細胞外泌體進行「工程化編輯」。藉由精準調控外泌體的表面結構與內含物(如包覆特定的微小 RNA 等關鍵修復訊號),我們將其轉化為具備強大修復潛能的新穎再生醫療藥物,協助在受損組織中重建適合再生的 niChe。
結合 DNA/RNA 摺紙技術的「精準結構設計」與 hiPSC 工程化外泌體的「高效生物傳遞」,我們期盼能突破現有框架,為再生醫療與退化性疾病帶來極具潛力的全新策略。
At the forefront of regenerative medicine, we are combining cutting-edge nanoscale molecular engineering with cell biology to pioneer breakthrough treatments. To achieve this, we are actively integrating "DNA/RNA origami" and "engineered exosomes" to build a next-generation biomedical R&D platform.
DNA/RNA Origami changes how we think about genetic material. We use DNA and RNA as highly flexible biomedical materials. Through precise computer modeling, we assemble them at the nanoscale into 3D structures with specific functions. This technology allows us to develop novel biomedical components, offering new approaches for precise targeting and tissue repair.
At the same time, cell-to-cell communication is essential for tissue regeneration. Exosomes—nanoscale vesicles naturally released by cells—are excellent delivery vehicles. Using advanced genetic engineering, we modify the exosomes derived from human induced pluripotent stem cells (hiPSCs). By precisely adjusting their surface structures and contents (such as loading them with specific microRNAs that signal repair), we transform them into powerful new regenerative medicines. This helps rebuild the ideal niChe for healing within damaged tissues.
By combining the precise structural design of DNA/RNA origami with the highly efficient biological delivery of engineered hiPSC exosomes, we aim to break through current limitations. We hope to bring highly promising new strategies to regenerative medicine and the treatment of degenerative diseases.
人類誘導多能幹細胞(human induced Pluripotent Stem Cell,簡稱 hiPSC)是近代生醫領域最具突破性的發展之一,它打破了細胞分化的單向性,為再生醫療與新藥開發帶來了革命性的改變。
1. 它是如何被發現的?hiPSC 技術是由日本科學家山中伸彌(Shinya Yamanaka)團隊所開發。2006 年,他們首次成功將成體小鼠的皮膚細胞「基因再程序化」,回溯到類似胚胎幹細胞的狀態;隨後在 2007 年,該團隊成功在人類細胞上實現這項技術,培育出人類誘導多能幹細胞。這項顛覆傳統生物學常理的重大發現,讓山中伸彌教授於 2012 年榮獲諾貝爾生理學醫學獎。
2. 製造方法 (細胞再程序化)hiPSC 的製造過程被稱為「細胞再程序化」(Cellular Reprogramming)。科學家會從人體採集少量的成體細胞(通常是皮膚纖維母細胞或血液細胞),並透過病毒載體或非病毒技術,將四個關鍵的轉錄因子(Oct3/4、Sox2、c-Myc、Klf4,學界常稱為「山中因子」)導入這些成熟細胞中。這四個因子能重新啟動細胞的基因表現,將已經分化定型的細胞「時光倒流」,誘導回具有多重分化潛能的原始幹細胞狀態。
3. 技術的重要性hiPSC 技術之所以在醫學界具有舉足輕重的地位,主要基於兩大無可取代的優勢:
避開倫理爭議: 過去具有多重分化能力的幹細胞主要來自人類胚胎(胚胎幹細胞, ESC),伴隨著巨大的倫理與道德爭議。hiPSC 是使用成體細胞進行培育,完美解決了這個問題。
高度的免疫相容性: 由於可以取用病患自身的細胞來培育,未來若將其誘導分化為特定組織並移植回病患體內,能大幅降低免疫排斥的風險,實現真正的「個人化醫療」。
hiPSC 擁有分化成人體幾乎所有細胞類型的能力,目前主要廣泛應用於以下領域:
再生醫療與組織修復: 可將 hiPSC 誘導分化為神經幹細胞、心肌細胞等,用於修復受損組織。例如在神經退化疾病的治療中,結合生醫材料重建適合細胞生長的 niChe,能大幅提升細胞存活率與神經再生效能。
新世代免疫療法: 利用 hiPSC 大量培育並衍生出標準化、具備量產潛力的 CAR-T 或 CAR-NK 免疫細胞,作為現成型(Off-the-shelf)的癌症治療武器。
疾病模型建立: 將帶有特定遺傳疾病患者的細胞誘導成 hiPSC,能在實驗室的培養皿中重現該疾病的發展過程,幫助科學家深入研究致病機制。
藥物篩選與毒性測試: 利用 hiPSC 衍生出的病理細胞進行新藥測試,不僅能提高藥物篩選的準確度與效率,還能大幅減少動物實驗的需求。