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

2. TOLEROGENIC IMMUNOMODULATION
T regs
Regulatory T Cells
MSCs
DIPIT
Vitamin D
Low Dose IL-2
Omega 3

3. for Infusion of MSCs in Subjects with Type 1 Diabetes
Interventional Radiology for Selective Targeting of Pancreatic Arteries
for Infusion of MSCs in Subjects with Type 1 Diabetes

5. MSCs in T1DM (DRI-Stanford/CIRM) Study Design
Enrollment
Month 6 Post T1D Diagnosis
MSC 2.5 x 106 cells/kg
Month 18
Crossover
Month 30
GROUP 1 (N=20)
MSC
Assessment
CONTROL
Assessment
GROUP 2 (N=20)
CONTROL
Assessment
MSC
Assessment
Placebo

6. Chronic Complications: Chronic Kidney Disease
End stage renal disease (ESRD) remains the major cause of excess morbidity and premature mortality in patients with T1D.
Despite almost universal implementation of renoprotective therapies and attempts to improve glycemic control, the risk of ESDR in T1D is not decreasing but increasing, suggesting that more effective therapies are needed.
U.S. Renal Data System (
Rosolowsky ET et al., J Am Soc Nephrol 2011; Krolewski AS et al., Diabetes Care 2015

7. U.S. Renal Data System (http://www.usrds.org/)
The number of new cases of ESRD almost doubled in patients aged yrs, suggesting that improved care has not reduced but postponed the onset of ESRD.
U.S. Renal Data System (
Rosolowsky ET et al., J Am Soc Nephrol 2011; Krolewski AS et al., Diabetes Care 2015

8. Interventional Radiology for Selective Targeting of Renal Arteries
for Infusion of MSCs in Subjects with Chronic Renal Disease
Overall ↑ in eGFR 2 months after injection. Deterioration between 12 – 18 months for advanced patients.
Patients with eGFR >35 at start (all in stage 3A and most in 3B), experienced long-term improvement.
Baseline
18 months
STAGE 3A
STAGE 3B
STAGE 4
STAGE 5
Vascular structural changes within the kidneys 2 months after the injection, reflected by a sustained reduction in the Renal Resistive Index (RRI) at both renal artery (hilar) and interlobar arteries.
Hilar artery
Interlobar artery
PRE-PROCEDURE
2 MONTHS POST-INJECTION

9. Encapsulated Islets-MSC Transplants
in a Biologic Resorbable Scaffold on the Omentum

10. Osp. Niguarda Ca’Granda
Allotransplantation of Microencapsulated Human Islets in T1D without Immunosuppression
Azienda Ospedaliera
Osp. Niguarda Ca’Granda
Milano

11. DRI Federation Protocol:
Allotransplantation in brittle type 1 diabetes mellitus (Niguarda Hospital, Milan, Italy)
Microencapsulation of human islets (University of Perugia, Italy)
Transplant in omentum (DRI, University of Miami BioHUB Protocol)
Peritransplant treatment with Omega-3 and Vit D (DRI, University of Miami Poseidon Protocol)
Oxygen (DRI, University of Miami Protocol)
Liraglutide treatment of recipients
No immunosuppression

12. 15%

13. THE AUTOIMMUNE EPIDEMIC
What role chemicals, heavy metals, viruses, diet, stress, lifestyle and genes play in developing autoimmune disease
How our modern lifestyles and environmental contamination have created a “perfect storm” — the ripest possible conditions for today’s autoimmune epidemic to take hold
The connection between autoimmune disease and allergies, the rates of which are likewise skyrocketing (

15. Healthy Lifespan Potential
Telomere Shortening:
Age
INFLAMMATORY DIET 1%
50%
100%
Healthy Lifespan Potential
ANTI-INFLAMMATORY DIET

16. Healthy Lifespan Potential
Telomere Shortening:
Age
INFLAMMATORY DIET 1%
50%
100%
Healthy Lifespan Potential
ANTI-INFLAMMATORY DIET

17. AA/EPA Ratio as Healthspan Predictor

18. The Perfect Nutritional Storm
Increased Omega-6
Increased Refined Carbohydrates
Decreased Omega-3
Decreased Polyphenols

19. Shared Tolerogenic Immunomodulation Pathways
MSC and T1DM
MSCs, Vitamin D, Omega 3
Shared Tolerogenic Immunomodulation Pathways
October 2014
MSCs
Vitamin D
Omega 3
Carlsson P-O , Schwarcz E, Korsgren O and Le Blanc K. Diabetes 2014 doi: /db , PMID:

24. TOLEROGENIC IMMUNOMODULATION
T regs
Regulatory T Cells
MSCs
DIPIT
Vitamin D
Low Dose IL-2
Omega 3