Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Advancements of Stem Cells in Diabetes TREATMENT or CURE ? Adeeb Al-Zoubi, Ph.D. Assistant Professor, College of Medicine , University of Illinois, USA CEO, Stem Cells of Arabia, Amman, Jordan No Conflict of Interest Declaration: I do not have any financial association with any of the manufacturers or suppliers of any material or equipment used in this presentation Adeeb M. AlZoubi, Ph.D. Cell Therapy Cell therapy is the transplantation of human or animal cells to replace or repair damaged tissue Cell Therapy vs. Stem Cell Therapy Cell Therapy Stem Cell Therapy Differentiated Cells Undifferentiated Stem Cells Cell Therapy – Differentiated Cells Cancer-Specific T Cells Our Work on Immunotherapy Against Cancer Purified Effector T Cells Specifically Killed Cancer Cells in vitro Integr. Mol. Med., 2015, 2(5):317-325 Stem Cell Therapy Undifferentiated Cells to repair damaged or diseased organ or tissue What are Stem cells? Immortal: Capable of self-renewal Can differentiate into other cell types and generate mature cells with specialized functions of a particular tissue Have homing capacity Self renewal and differentiation are controlled by intrinsic and extrinsic factors. SelfRenewal Differentiation Al-Zoubi et.al., Cell Transplant. 2010 Al-Zoubi et.al., J. Neurorestoratology, 2016 Neuron Stem Cell Potentiality Totipotent Pluripotent Multipotent Unipotent Embryonic SC: •Developing embryo Fetal SC: •Developing fetus •Amniotic fluid Adult SC: •Umbilical cord •Bone marrow •Peripheral blood •Tissue Resident Adult Stem Cells in Research & Therapy 1. Source & Type Clinical: •Bone Marrow •Blood •Tissues •Cord Blood • Hem/Onc • Immu. Diseases • Cardiac 2. Processing • Hepatic disorders • Purification • Neurological • Expansion • Diabetes •Manipulation • Blindness 3. Next • Infertility --Transplantation • Skin -- Research • Others Research: Mechanisms: • Differentiation • Repair • Renewal • Homing • Others Clinical Trials on Stem Cells 5182 World-wide Studying Genetics of Cells ~ 20 Years Ago In Chicago ~ 12 Years Ago In Chicago Stem Cell Differentiation Studies 2007-2016 in Jordan and USA Published: AlZoubi et.al., Cell Transplant. 2010;19(2):193-202. Published: AlZoubi et.al., Stem Cell Res. Ther. 2013; 25;4(1):16. Published: AlZoubi et.al., Cell Transplant. 2014; 23: 25-34. Published: AlZoubi et.al., Integr. Mol. Med. 2015; 2(5):317-325 Published: AlZoubi et.al., J. Neurorestoratology, 2016 Sponsored by Stem Cells of Arabia As of March, 2016 U.S. ClinicalTrials.gov # NCT02641769. Intra-Testicular Transplantation of Autologous Stem Cells for Treatment Azoospermia Male Infertility. U.S. ClinicalTrials.gov # NCT02644759. Transplantation of Autologous Stem Cells for the Treatment of Type 1 Diabetes Mellitus. U.S. ClinicalTrials.gov # NCT02687672. Transplantation of Autologous Bone Marrow Stem Cells for Treatment of Spinal Cord Injury. U.S. ClinicalTrials.gov # NCT02638714. Treatment of Optic Neuropathies Using Autologous Bone Marrow-Derived Stem Cells. U.S. ClinicalTrials.gov # Pending. Autologous Bone Marrow-Derived CD34+, CD133+, and CD271+ Stem Cell Transplantation for Retinitis Pigmentosa. Stem Cells in Jordan • ~8 M Population • + ~3M regugees • Serving > 50 M • Central location • Politically stable • Ranked 1st in the ME and 5th WW for Medical Tourism (W.H.O.) • Ministry of Health • Jordan FDA • Jordan Medical Association Medical Facilities: • Royal Medical Services • MOH Hospitals • Academic Institutions • Private Hospitals األردن أول دولة عربية تصدر نظام وتعليمات للعمل بالخاليا الجذعية New Stem Cell Law in Jordan, 2014 New Guidelines in February, 2016 Methods Used to Obtain ASCs MSCs: Adherence Properties Fat-Derived SCs: Lipo-Aspiration Mononuclear cells: Leukapheresis Pure Populations: Specific SC Markers CD 34+ Widely characterized HSC CD133+ Non-Hem. Potential CD271+ Neuronal potential Clinical-Grade Purification of Human Stem Cells 30-50 nm • FDA Approved • CE-marked • Clinically tested W W The Jordanian Method for Treatment of Chronic Conditions 99% ® Tissue Regeneration and Organ Repair Using Specific Autologous SC Combinations Purified and Prepared by Approved Methods Cell Transplant. 2014;23:S25-34. Epub 2014 Nov 4. The Jordanian-American Method for Treatment of Diabetes 99% ® • Registered Trade Mark at Jordanian Ministry of Industry and Commerce • U.S. ClinicalTrials.gov # NCT02644759. Transplantation of Autologous Stem Cells for the Treatment of Type 1 Diabetes Mellitus Pancreatic Protection By Immune Modulation AND Cell Restoration By Autologous Stem Cells Treatment of Type I Diabetes With Immunomodulation and Autologous Purified Stem Cell Transplantation: The Jordanian Experience U.S. ClinicalTrials.gov # NCT02644759. University of Illinois College of Medicine Adeeb Al-Zoubi, Hazem Haboob, Sameh Al-Bakheet, Marwa Tapponi, Mahasen Zalloum, Samer Abu Radi, Farah Khalifeh, Shahed Sarayrah, Feras AlTwal, Mohammed El-Khateeb, Mark Holterman In Chicago: The Immune Response Leading to T1DM DCs and Ms infiltrate the iselets DCs & Ms Present cell Ags/MHC-II to CD4+ T cells Activated Ms secrete IL-12 Activation of Th1 cells Release of GrB, perforin & FasL Secretion of IFN and IL-2 CD8+ T cells differentiate into CTLs CD8+ T cells recognize cell Ags/MHC-I on CD4+ T cells Cell Apoptosis Migration of CD8+ T cells to iselets IL-2 activate resting Ms Up-regulation of IL-1 and TNF > 38,000 Publications on Stem Cells and Diabetes Currently, 157 clinical trials are registered for use of stem cell in diabetes March, 2016 No Cure for Type 1 Diabetes The Modified Jordanian Method Step 1: Collection of PB-MNC by Leukapheresis 1 Step 2: Purification of CD34+/CD133+/CD271+ autologous Stem Cells 2 Step 3: A: Transplantation of purified autologous CD34+/CD133+/CD271+ Stem Cells via Interventional Radiology B-1: T Cell Education of autologous PB-MNCs by CB-MSCs B-2: Transplantation of Educated autologous PB-MNCs intravenously Phase I: Pilot Study 2011-2015 4 Patients Date of SCT Age 9-2011 45 89 M No No 1-2012 52 67 M No No 4-2013 32 77 M Yes No 2-2014 12 31 F No No Weight M/F Smoking Alcohol Results: Daily Insulin Intake 18 months after Trx. Before After Insulin intake (Units) 80 70 60 50 40 30 20 10 0 1 2 3 Patient 4 Results: C-Peptide 1.4 Before After 1.2 1 0.8 0.6 0.4 0.2 0 1 2 3 Patient 4 Results: HbA1c 14 Before 12 After 10 8 6 4 2 0 1 2 3 Patient 4 Other Follow Up Criteria- Lab • Kidney function test : Urinalysis ( chemical exam : albumin , sugar , acetone , bilirubin , urobilinogen , bile salts , blood , nitrite . microscopic exam : R.B.C , pus cells , clumps , cast , crystals , epithelial cells , mucus , bacteria . ) , Urea , creatinine , uric acid , total protein , albumin , globulin , Na , K , Cl • Liver : Bil.( total , direct ) , ALK. Phosphatase , SGPT , SGOT , total protein , Albumin , Globulin , Amylase . • Lipid : Triglycerides , Cholesterol , HDL , LDL • Cardiac : CPK , CK.MB • Diabetes : FBS , RBS , C-peptide , HbA1C , insulin , glucagon , anti insulin antibodies , anti islets antibodies , anti beta cells antibodies , anti gat antibodies , Lithium, IGF-1 , TSH . • Hematology : hemoglobin , RBC , MCV , MCH , MCHC , WBC count , Neutrophils , Lymphocytes , Monocytes , Eosinophils , Basophils , Platelet count , Ca , Phosphorus , iron , TIBC , Ferritin . • Others : FSH , LH , Cortisol , ACTH , Testosterone , Vitamin D Phase II: Efficacy Study 2015-2018 Number of patients done: 16 patients since July, 2015 Early follow up: No complications Early signs of improvements HbA1c C-Peptide Insulin dependency Quality of Life (QoL) Target number of patients to be studied 50 patients Conclusion Executing clinical trials is a long process and requires extensive experience. Treatment of chronic conditions with the Jordanian Method is SAFE Efficacies and success rates depend on many factors More research needs to be performed in order to draw more solid conclusions Stem Cells of ArabiaTeam-2015 Jordan USA Sweden France France USA Germany Canada Thank You