研究團隊從需要氣管移植的病人身上取下少量細胞，轉化為誘導性多功能幹細胞(induced pluripotent stem cell, iPSC)。體外大量培養這些幹細胞後，使之附著到客製化的3D列印氣管支架上。最後誘導這些幹細胞分化成為氣管相關細胞，形成可供移植的仿生氣管。
Free to breathe:
A new turning point of tracheal transplant
Tracheal reconstruction using artificial trachea is still a great challenge in thoracic medicine. With the advances of tissue engineering technology, stem cell biology, and 3D printing technology, the engineered bionic trachea that mimics tracheal anatomy and functions like human trachea have the potential to overcome the clinical barrier and regenerate tracheas. It begins with taking few cells from the patient needing tracheal reconstruction, and then transforming these cells into induced pluripotent stem cell. After in vitro cell expansion culture, the obtained stem cells will be transferred to a custom- designed 3D-prineted stent. Eventually, the stem cells on the stent will be induced and differentiated to mature trachea-related cells, becoming the bionic trachea ready for transplantation. Under the supports from Taiwan MOST, we recruited professors and doctors who major in automated intelligence, biomechanics, materials science, stem cell biology, medicine, and clinical ethics and work together to make the dream of bionic trachea come true.
For in vitro cell expansion, we designed automated robotic arm to perform daily works in cell culture. There are two advantages: 1) to reduce the workload by human, allowing researchers to do real researches but boring repetitions; 2) to avoid bacterial pollution from human, ensuring the safety in clinical applications. We also developed Artificial Neural Network for cell culture quality control. The obtained data will be fed back to robotic arm to responsively adjust the culture conditions. Therefore, our robotic arm is not only automated but also intellectualized.
For promotion of stem cell proliferation/differentiation, we developed techniques and equipments based on ultrasound (US). US can deliver mechanical waves into cells, inducing responses inside the cells. By using our US equipments, we are the first one to visualize the US-induced cell activation. We saw lamellipodial, a typical response for cell activation, 10 minutes after US application.
After preparation of stem cells with high quality, we then need stent to enclose these stem cells. Therefore, we developed bio-degradable stent material, which is suitable for human transplantation. This stent is multi- functions: its fine structure with patent allows the growth of stem cells and enclosure of small molecule drugs, thereby promoting regeneration of tracheal tissue. Moreover, out stent is 3D-printed, which is also custome- made when basing on medical imaging for individual patient.
The aforementioned preclinical techniques and equipments has patent and technological transfer. In addition, animal study has been proceed and clinical study will be started soon as the proof of concept of engineered bionic trachea.
陳晉興醫師 Jin-Shing Chen
Department of Surgery, National Taiwan University and National Taiwan University Hospital, Taipei