Professor of the Institute for Tissue Engineering and Regenerative Medicine
Office: (852) 3505 2723
Address: Rm 74037, 5/F, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, N.T., Hong Kong
ORT Website: http://www.ort.cuhk.edu.hk/staff-oscarlee.html
Prof. Oscar Lee’s major research interest is to study the plasticity of Mesenchymal Stem Cells (MSCs) and its therapeutic potential on treatment of musculoskeletal diseases such as osteoporosis, sarcopenia and bone tumor, and also liver diseases. Through integration of knowledge in stem cell biology, immunology, bioengineering and computer sciences, his ultimate goal is to develop advanced technologies in regenerative medicine, artificial intelligence and precision medicine for diagnoses and treatments of the diseases so as to benefit to patients.
Contributions to Science and Selected Publications
A. Induction of MSC Differentiation by microenvironments and mechanical stimuli for tissue regeneration
Prof. Lee’s research team has been studying on how physical properties of the microenvironments, including three-dimensional spherical spatial boundary conditions, substrate stiffness, and mechanical forces contribute to the regulation of MSC differentiation over the years. They have used biophotonic approaches, such as Surface Plasmon Resonance Biosensor and Raman Spectroscopy, to monitor the differentiation of stem cells in a label-free & real-time manner.
- Chu SY, Chou CH, Huang HD, Yen MH, Hong HC, Chao PH, Wang YH, Chen PY, Nian SX, Chen YR, Liou LY, Liu YC, Chen HM, Lin FM, Chang YT, Chen CC* & Lee OK*. “Mechanical stretch induces hair regeneration through the alternative activation of macrophages.” Nat Commun, 2019; 10(1):1524.
- Wu HH, Ho JH, Lee OK*. “Detection of hepatic maturation by Raman spectroscopy in mesenchymal stromal cells undergoing hepatic differentiation. ” Stem Cell Res Ther, 2016; 7(1):6.
- Yen MH, Wu YY, Liu YS, Rimando MG, Ho JH*, OK Lee*. “Efficient generation of hepatic cells from mesenchymal stromal cells by an innovative bio-microfluidic cell culture device.” Stem Cell Res Ther, 2016; 7(1):120. (Cover Feature)
- Hsieh WT, Liu YS, Lee YH, Rimando MG, Lin KH, Lee OK*. “Matrix dimensionality and stiffness cooperatively regulate osteogenesis of mesenchymal stromal cells.” Acta Biomater, 2016; 32:210-22.
- Liu YS, Liu YA, Huang CJ, Yen MH, Tseng CT, Chien S, Lee OK*. “Mechanosensitive TRPM7 mediates shear stress and modulates osteogenic differentiation of mesenchymal stromal cells through Osterix pathway.” Sci Rep, 2015; 5:16522.
- Shih YV, Hwang YS, Phadke A, Kang H, Hwang N, Caro EJ, Nguyen S, Siu M, Theodoraki EA, Gianneschi N, Vecchio K, Chien S*, Lee OK*, Varghese S*. “Calcium-phosphate bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling.” P Natl Acad Sci USA, 2014; 111(3):990-995.
- Kuo YC, Chang TH, Hsu WT, Zhou J, Lee HH, Ho JH*, Chien S*, Lee OK*. “Oscillatory shear stress mediates directional reorganization of actin cytoskeleton and alters differentiation propensity of mesenchymal stem cells.” Stem Cells, 2015; 33(2):429-42
- Kuo SW, Lin HI, Ho JH, Shih YR, Chen HF, Yen TJ*, Lee OK*. “Regulation of the fate of human mesenchymal stem cells by mechanical and stereo-topographical cues provided by silicon nanowires.” Biomaterials, 2012; 33(20):5013-5022.
- Kuo YC, Ho JH, Yen TJ, Chen HF, Lee OK*. “Development of a surface plasmon resonance biosensor for real-time detection of osteogenic differentiation in live mesenchymal stem cells.” PLoS ONE, 2011; 6(7):e22382.
B. MSCs Isolation and Hepatic Tissue Engineering
Prof. Lee’s first important research achievement was the discovery of differentiation potential of stem cells from mesodermal origin into hepatocytes of endodermal origin, and being the first to design a novel 2-step protocol to induce hepatic differentiation of MSCs, and have obtained two US patents for this finding (US 8062632B2, US8216839B2). He has demonstrated that MSC transplantation effectively promotes liver regeneration, reverses liver damage, and reduces mortality in mice. Moreover, he has also developed a unique three-step protocol that effectively induces hepatic differentiation of iPS cells, and have secured one US and one TW patent (US9732323B2, TWI449789B). His research group has also adopted a novel method of cryo-chemical decellularization of the whole liver which opens a new area of MSCs-based functional hepatic tissue engineering.
- Lee CW, Chen YF, Wu HH, Lee OK*. “Historical Perspectives and Advances in the Mesenchymal Stem Cell Research for the Treatment of Liver Diseases.” Gastroenterology, 2018; 154(1):46-56.
- Lee CW, Huang WC, Huang HD, Huang YH, Ho JH, Yang MH, Yang VW, Lee OK*. “DNA methyltransferases modulate hepatogenic lineage plasticity of mesenchymal stromal cells.” Stem Cell Reports, 2017; 9(1):247-263.
- Jiang WC, Cheng YH, Yen MH, Chang Yin, Yang VW, Lee OK*. “Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering.” Biomaterials, 2014; 35(11):3607-3617.
- Chen YF, Tseng CY, Wang HW, Kuo HC, Yang VW, Lee OK*. “Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol.” Hepatology, 2012; 55(4):1193-1203.
- Kuo TK, Hung SP, Chuang CH, Chen CT, Shih YV, Fang SY, Yang VW, Lee OK*. “Stem cell therapy for liver disease: Parameters governing the success of using bone marrow mesenchymal stem cells.” Gastroenterology, 2008; 134(7):2111-2121. (editorial highlight)
- Lee KD, Kuo TK, Whang-Peng J*, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK*. “In vitro hepatic differentiation of human mesenchymal stem cells.” Hepatology, 2004; 40(6):1275-1284. (editorial highlight)
- Lee OK*, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH. “Isolation of multipotent mesenchymal stem cells from umbilical cord blood.” Blood, 2004; 103(5):1669-1675 (Cover Feature)
C. Clinical Application of MSCs
An endeavor to investigate the role of hMSCs in regulating hematopoietic stem cell fate and their therapeutic potential to treat lupus nephritis, spinocerebellar ataxia and diabetes in different animal models, and has established clinical trials of systematic administration of MSCs for treatment of osteoarthritis, acute liver failure and spinocerebellar ataxia in patients.
- Tsai YA, Liu RS, Lirng JF, Yang BH, Chang CH, Wang YC, Wu YS, Ho JH, Lee OK*, Soong BW*. “Treatment of spinocerebellar ataxia with mesenchymal stem cells: A phase I-IIa clinical study.” Cell Transplantation, 2017; 26(3):503-512.
- Ji AT, Chang YC, Fu YJ, Lee OK*, Ho JH*. “Niche-dependent regulations of metabolic balance in high-fat diet induced diabetic mice by mesenchymal stromal cells.” Diabetes, 2015; 64(3):926-36.
- Chang YK, Chen MH, Chiang YH, Chen YF, Ma WH, Tseng CY, Soong BW, Ho JH*, Lee OK*. “Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells.” J Biomed Sci, 2011; 18(1):54.
- Chang JW, Hung SP, Wu HH, Wu WM, Yang AH, Tsai HL, Yang LY, Lee OK*. “Therapeutic effects of umbilical cord blood-derived mesenchymal stem cell transplantation in experimental lupus nephritis.” Cell Transplantation, 2011; 20(2):245-57.