M.D. Kaohsiung Medical College
Ph.D. University of Washington, Seattle (Bioengineering)
Although the field of cardiac stem cell therapy has significantly advanced over the past years, the premise of regenerating or replacing diseased human myocardium with functional tissue remains unsatisfied. The overall objective of our research is to promote myocardial stem cell therapy through nano-/micro-environmental engineering the intramyocardial stem cell niche for endogenous cardiac stem cells to reactivate, proliferate, differentiate and repopulate the diseased myocardium. Using a cardiac specific inducible Cre-Lox transgenic mouse strain, we have found that an endogenous cardiac stem cell pool may contribute to ~15% of new cardiomyocytes in the peri-infarcted area, saturated as early as within the first 2 weeks after infarction. Accordingly, we focus on (1) animal models to identify the source of this cardiac stem cell pool, and (2) methods to engineer the cardiac nano-/micro-environments for augmenting the regenerative signaling for spontaneous repair. Thus, we employ a team approach which brings together people from a broad variety of backgrounds, including stem biology, engineering and medicine . This combination has allowed us to work together and interact in a way traditionally not available at an individual laboratory or program.
利用誘導性心肌細胞標的基因轉殖鼠進行成鼠心肌細胞血統追蹤,本實驗室發現老鼠在自然老化過程中,原有的心肌細胞並不會藉由幹細胞分化進行新陳代謝。研究卻顯示了令人驚訝的結果,當心肌梗塞發生之後二週內,在梗塞周圍的心肌細胞竟有多達15%左右是由幹細胞衍生而來。證明成年哺乳類動物的心臟可能仍然具有某些再生的能力。本實驗室藉由結合生物、醫學、工程三個領域的轉譯研究,以改進幹細胞在受損心肌中的物理、化學、機械與生物的奈微環境,同時開發新型的奈米生醫材料進行基因轉殖與藥物釋放,以幫助幹細胞形成成熟而有功能的心臟組織,達成真正的心肌再生。近年,本實驗室利用奈米纖維水膠(NF)結合血管內皮生長因子(VEGF)形成NF/VEGF的混合藥物,並注射到受損心肌部位。一方面克服了生長因子單獨使用造成的血管滲漏、致癌等副作用。二方面可提升梗塞後的心功能,減少梗塞面積等。更驚人的是,這個微環境還會引發心肌再生,打破傳統認為心肌無法再生的觀念。