Effect of Microvesicles and Exosomes Therapy on β-cell Mass in Type I Diabetes Mellitus (T1DM)
Effect of Microvesicles and Exosomes Therapy on β-cell Mass in Type I Diabetes Mellitus (T1DM)
Type 1 diabetes mellitus is strictly autoimmune mediated disease destructing the islets
 β-cell of the pancreas. Mesenchymal stem cells and its microvesicles are reported as an
 anti-inflammatory agents. We hypothesis that intravenous infusion of cell free umbilical
 cord-blood derived MSC microvesicles may reduce the inflammatory state and hence improve the
 β-cell mass as well as the glycemic control of the patients of T1DM.
-  Twenty T1DM patients, age between 18-60 years with reduction of C-peptide chain more
 than 50%, C-peptide of more than 0.8 ng/mL at Screening and requiring insulin ≥0.4 IU
 per kg per day.

 -  Twenty T1DM patients of the same entry selection criteria will be subjected to all steps
 except the microvesicles administration as a control group.

 -  Study follow up period: Three months

 -  Gender: Both males and females are included

 -  Entry selection criteria include:

 UACR less than 300, BUN between 10-20 mg/dl, serum creatinin between 0.6-1.4 mg/dl and normal
 liver enzymes, normal serum bilirubin, normal serum albumin and coagulation profile).
 C-peptide of more than 0.8 ng/mL at Screening. BMI 20-40 kgm/m2 - Exclusion criteria: Other
 autoimmune diseases. Pregnancy. Previous treatment with stem cells. All patients and controls
 will be investigated for HBV, HCV & HIV by PCR test before enrollment in the study and
 positivity for any of these parameters means exclusion of this patient from the study.

 - The primary end point will be the end of three months follow up. At day (0):All patients
 and controls will be subjected to the following investigations: Liver functions tests, kidney
 functions tests, HbA1c, glucose tolerance test (GTT), fasting and 2 hrs.post prandial blood
 glucose levels, C-peptide chain level and calculated total daily insulin dose.

 After three months (at the end of the study) the same investigations will be repeated.

 Two intravenous infusions of cell free cord-blood derived mesenchymal stem cells [CB-MSC]
 microvesicles:

 - The first dose will be purified exosomes, ranging between 40-180 nm, in a dose of the
 supernatant produced from (1.22-1.51) × 10 (6)/kg/IV.

 (Characterization of exosomes:CD63, CD9, Alix, TSG 101, HSP 70).

 - The second dose, after 7 days, will be the microvesicles, ranging between 180-1000 nm, in a
 dose of the supernatant produced from (1.22-1.51) × 10 (6)/kg/IV.

 (Characterization of microvesicles: (Annexin V, Flotillin-2, selectin,integrin, CD40
 metalloproteinase).
Inclusion Criteria:

 -  UACR less than 300, BUN between 10-20 mg/dl, serum creatinin between 0.6-1.4 mg/dl and
 normal liver enzymes, normal serum bilirubin, normal serum albumin and coagulation
 profile). C-peptide more than 0.8 ng/mL at Screening. BMI 20-40 kgm/m2.

 Exclusion Criteria:

 -  Other autoimmune diseases. Pregnancy. Previous treatment with stem cells. All patients
 and controls will be investigated for HBV, HCV & HIV by PCR test before enrollment in
 the study and positivity for any of these parameters means exclusion of this patient
 from the study.