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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 Ms
infiltrate the
iselets
DCs & Ms
Present  cell
Ags/MHC-II to
CD4+ T cells
Activated Ms
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 Ms
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