1. Camillo Ricordi, MD, FNAI
Terapie Cellulari, Immunomodulazione e Medicina Rigenerativa per la Cura del Diabete
Camillo Ricordi, MD, FNAI
Director, Diabetes Research Institute and Cell Transplant Center
University of Miami
Chairperson, NIH CIT SC
Fellow, National Academy of Inventors

3. MILAN, BOLOGNA, ROME, PALERMO
DRI FEDERATION
UMEA
EDMONTON
OXFORD
STOCKHOLM
UCSF
GENEVE
MILAN, BOLOGNA, ROME, PALERMO
HACKENSACK
TIBLISI
STANFORD
VALENCIA
SHANGHAI-FOUZO
MIAMI
MANAGUA
SEOUL
TEL AVIV
KYOTO
SAN PAULO
BUENOS AIRES

4. 30 Years of the Ricordi Chamber
1988 – 2018
30 Years of the Ricordi Chamber
(Diabetes, 1988)

6. 1991 

7. TRANSPLANTATION OF
INSULIN PRODUCING CELLS
FOR TREATMENT OF DIABETES

8. IND 9336 Preclinical data Manufacturing information
Detailed Clinical protocols
Investigator information
Informed consents
Assurances: IRB, IND
IND 9336
-We are in the process of submitting data of the CIT Phase III clinical trial
-Animal Pharmacology and Toxicology Studies - Preclinical data
-Manufacturing Information
-Clinical Protocols and Investigator Information - Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. 
-Qualifications of clinical investigators, commitments to obtain informed consent from the research subjects,
-to obtain review of the study by an institutional review board (IRB), and
-to adhere to the investigational new drug regulations.
Biologic License Application
Diabetes Care 2016 Jul;
39(7):

9. Manufacture of a Complex Cellular Product
Eight manufacturing centers jointly developed and implemented a harmonized process for the manufacture of an allogeneic purified human pancreatic islet product.
Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, islet product specifications, certificate of analysis, and test methods.
The process was compliant with cGMP and cGTP.
No adverse events attributable to the product and no cases of primary nonfunction were observed in 48 patients participating in the CIT-07 Phase 3 trial.
Diabetes 2016 Nov;65(11):

10. Primary Endpoint
Proportion of subjects with HbA1c < 7.0% at day AND free of severe hypoglycemic events from Day 28 to Day 365 inclusive following the first islet transplant
Multiple secondary endpoints for safety and efficacy
Diabetes Care 2016; 39:

11. Primary Endpoint
Diabetes Care 2016; 39:

12. HbA1c [%]
Diabetes Care 2016; 39:

13. % of Patients with SHE
Diabetes Care 2016; 39:

14. Islet Allograft Survival
CONFIDENTIAL
UNPUBLISHED OBSERVATIONS

15. Proposed treatment algorithm for patients with T1D and problematic hypoglycemia.
MDI: Multiple Daily Injections
SMBG: Self Monitoring Blood Glucose
CSII: Continuous SC Insulin Infusion
SAP: Sensor S\Augmented Pump
LGS: Low Glucose Suspend
Proposed treatment algorithm for patients with T1D and problematic hypoglycemia.
Routinely provide to all MDI therapy patients with T1D using SMBG structured and curriculum-based educational programs that reduce the incidence of SH and restore awareness in a significant proportion of patients with IAH.
Add one diabetes technology, preferably CSII with SMBG or MDI with CGM, where available, with appropriate education, training, and support to patients with problematic hypoglycemia to reduce the incidence of SH and maintain or improve HbA1c.
Use SAPs, preferably with an automated threshold-suspend feature, where available, or very frequent contact with a specialized hypoglycemia service in patients whose problematic hypoglycemia persists despite the use of structured education and other diabetes technologies.
Consult with transplant program (and payer) about the eligibility of selected patients with persistent problematic hypoglycemia for an islet or a pancreas transplant when other interventions have not been effective and when the risk-benefit ratio is deemed favorable.

16. Specialist Hypoglycaemia Service
Outcomes for Adults with Type 1 Diabetes Referred with Severe Hypoglycaemia and/or Referred for Islet Transplantation to a
Specialist Hypoglycaemia Service
M.L. Byrne, D. Hopkins, W. Littlejohn, R. Beckford, P. Srinivasan, N. Heaton, S.A. Amiel, P. Choudhary
King’s College London
Horm Metab Res 2015; 47 (01): 9-15
47.2% of patients presenting with problematic hypoglycaemia resolved with optimal medical therapy, with a further 25% achieving clinically relevant improvement, however 27.8% required transplantation despite access to all therapies.

17. QOL www.thelancet.com/diabetes-endocrinology
Published online May 15,
QOL
Figure 4: Median gain in quality-of-life dimensions assessed with the Diabetes Quality of Life questionnaire
Quality of life was assessed at 6 months after first islet infusion in the immediate transplantation group and at
6 months after randomisation in the insulin group and compared with baseline. *No statistical tests were applied
because of the low number of respondents to this item.

18. HbA1c
% PTS with HbA1c <7
C-Peptide
Insulin Requirements

19. Data on 16,061 patients updated between 2013 and 2014.
Overall average HbA1c was 8.4 ± 1.6%, in patients 30 to 65 yrs of age it was between %.
ADA HbA1c goals of <7.0% were met by 14% of year-olds and by 30% in older adults.
About 60% of patients used insulin pumps; 7% used CGM.

21. MSCs in the DRI BioHUB Strategy
OPTIMIZATION
OF THE
TRANSPLANT
SITE
TOLERANCE INDUCTION
REVERSAL OF AUTOIMMUNITY
IMMUNOISOLATION
SOURCE
OF INSULIN PRODUCING CELLS
BIOLOGIC
CURE

24. Bioengineering of an Intraabdominal Endocrine Pancreas

25. In vivo studies in NonHuman Primates, models of diabetes, are ongoing
Version 2.0
In vivo studies in NonHuman Primates, models of diabetes, are ongoing
Thrombin
Plasma + MSC
Thrombin
Plasma + MSC
Islets
Omental surface