Strategic Research Development in Stem Cell and Regenerative Medicine in HKU Professor Sum-ping Lee Dean HKU Li Ka Shing Faculty of Medicine
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1 Strategic Research Development in Stem Cell and Regenerative Medicine in HKU Professor Sum-ping Lee Dean HKU Li Ka Shing Faculty of Medicine Adult stem cells Cells that are capable of self renewal and can differentiate and replace damaged or aged tissue 1
2 What is Stem Cell Therapy? Stem cell therapy- a treatment in which mature (adult) or immature stem cells are used to treat human diseases, e.g.bone marrow cell transplantation for leukemia Source: NIH Bone, joint, spine injuries & degeneration 29.8% 30.6% Stem cells Brain and nervous 14.2% system degeneration (including eye diseases) 18.2% Diabetes Others: 7.2% Target for Regenerative Medicine Heart Diseases 2
3 Stem Cell Treatment for Eye Diseases Professor David Wong Albert Young Chair Professor of Ophthalmology Director Eye Institute Stem cell therapy is directed at treating corneal and retinal diseases 3
4 Corneal stem cells Limbal stem cell deficiency (LSCD) Result from trauma such as lime burn or inflammatory disease Leads to scarring and the growth of new blood vessels; as a result the cornea turns opaque or white Existing therapy When one eye is affected, stem cell transplant from one eye to the other is possible But this could lead to stem cell deficiency in the donor endangering a previously healthy eye When both eyes are affected, treatment relies on allografts from live related donors or from cadaveric eyes 4
5 Age-related macular degeneration 5
6 Patch graft in myopic macular degeneration Surgery relies on harvesting patient s own tissue from the periphery and transplanted into the centre 6
7 Source of adult stem cells in the eye Ciliary Body Retinal Progenitor Cells can turn into all cell types normally found in the retina Can grow into all cell types that make up the retina 7
8 Growing cells on substrates eptfe as substrate Transplant strategy 8
9 NSFC/RGC Funding ipsc Project Generation of corneal epithelial stem cells from human induced pluripotent stem cells (ipsc) and application for corneal epithelial tissue engineering Epithelial defects-cloudy cornea-vision loss Background ---Corneal stem cell (CSC) at limbal is the cell source for corneal epithelium regeneration. ---Transplanting CSC restores vision in those patients with limbal stem cell deficiency (LSCD). Major Challenges --shortage of available donor tissues --Immune rejection Proposed Solutions Using induced pluripotent stem cells or ipscs, to generate patient-specific corneal epithelial stem cells. Patient s stromal cells Deriving Corneal epithelial stem cells Tissue engineering Treatment ips generation Advantages --Patient-specific --Batch to batch consistenc -- No ethical issues --Unlimited cell source -- Cost effective 9
10 Investigators Hong Kong Team University of Hong Kong Main Land Team XiaMen University Qizhou Lian Hung-Fat Tse David S H Wong Chung-Wah Siu ZuGuo Liu Wei Li Hui Lin Cheng Li Carol Shan-Yu Stem Cell Treatment for End-Stage Heart Failure Professor Hung-Fat Tse William MW Mong Professor in Cardiology Cardiology Division Department of Medicine University of Hong Kong 10
11 Heart Failure After Acute Myocardial Infarction: A Lost Battle in the War on Heart Failure NEJM Heart Failure (HF) After Acute Myocardial Infarction (MI): A Lost Battle in the War on Heart Failure Percentage of Events (%) Congestive Heart Failure MI Death 5-year mortality for HF ~50% HF death ~135% ( ) Hospital discharge ~160% ( ) AHA Statistical update Velagaleti RS, et al, Circulation
12 No-Option Patients with Coronary Artery Disease (CAD) Bone Marrow Cell Therapy Re-endothelization Angiogenesis Sata: Arterioscler Thromb Vasc Biol, 2006; 26:
13 Treatment of Heart Diseases Reimplantation World s First Catheter-based Autologous Bone Marrow Stem Cells Implantation in Human GMP Laboratory Tse et al. Lancet 2003 Flow cytometry Catheter-Based Intramyocardial Injection 13
14 Prospective Randomized Trial of Direct Endomyocardial Implantation of Bone Marrow Cells for Therapeutic Angiogenesis in Coronary Artery y Disease (PROTECT-CAD) CAD) : Study Design No-option CAD pts (n=28) Control group 2:1 RANDOMIZATION BM group Saline Injection (n=9) BM MNC* Injection (n=19) MNC 1x10 7 ml -1 (n=10) MNC 2x10 7 ml -1 (n=9) 6 months Assessment * Bone Marrow Mononuclear Cell Tse HF, et al. Eur Heart J 2008 Exercise Time (s) PROTECT-CAD: CAD: Main Result ±136 Exercise Time Δ+20.9%* P=0.026 Δ-18.0% *p< ± ± ±228 0 BMC=19 Placebo =8 Baseline 6 months Baseline 6 months Tse HF, et al. Eur Heart J
15 70 PROTECT-CAD: CAD: Results Left Ventricular Ejection Fraction Δ+7.6%* Δ+4.6% *p<0.01 LVEF (%) ±9 56±9 48±8 49±8 20 BMC (n=18) Placebo (n=7) 10 0 Baseline 6 months Baseline 6 months Tse HF, et al. Eur Heart J 2008 END -Heart Failure: Study Design Control group No-option CAD and HF pts (n=90) 2:1 RANDOMIZATION Hong Kong Indonesia Australia BM group Saline Injection (n=30) BM MNC Injection (n=60) MNC 3x10 8 ml -1 6 months Assessment (MRI-EF) This research is supported by the SK Yee Medical Foundation. 15
16 Cardiac MRI Assessment Baseline 6 months Clinical Trials for Stem Cells Therapies in Heart Diseases Total no. of studies: 333 Asia countries: <10% ClinicalTrials.gov 16
17 - Q & A - 17
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