Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin.
BACKGROUND
Type 1 diabetes mellitus (DM) is an autoimmune disorder with disturbed glucose/insulin metabolism, which has no medical treatment other than life-long insulin therapy, despite which 30% of subjects develop organ failure. Herein we have reported the use of human adipose-tissue-derived, insulin-making mesenchymal stem cells (h-AD-MSC) transfused with unfractionated cultured bone marrow (CBM) in 5 insulinopenic DM patients.


METHODS
Five (M:F, 2:3) insulinopenic DM patients of 0.6 to 10 years' duration, ages 14 to 28 years under treatment insulin (Human with 14-70 U/d) showed postprandial blood sugars between 156 to 470 mg%, glycosylated hemoglobin 6.8% to 9.9% and c-peptide levels of 0.02 to 0.2 ng/mL. They underwent intraportal administration of xenogeneic-free h-AD-MSC (mean dose = 1.5 mL; cell counts, 2.1 x 10(3)/muL). The CD45-/90+/73(+) cells (29.8/16.8%) showed c-peptide levels of 3.08 ng/mL, insulin level of 1578 micro IU/mL. The aliquot was supplemented with CBM (mean dose 94 mL with cell counts: 18.7 x 10(3)/microL) containing CD45-/34+ elements of 0.93%. The Institutional Review Board approved the study protocol and consent forms.


RESULTS
All patients were successfully infused CBM plus h-AD-MSC without any untoward effects and showed 30% to 50% decreased insulin requirements with 4- to 26-fold increased serum c-peptide levels, with a mean follow-up of 2.9 months.


CONCLUSIONS
This report describes safe and effective treatment of insulinopenic diabetics using insulin-producing h-AD-MSC plus CBM without xenogeneic materials.
Department of Nephrology and Transplantation Medicine, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre, Dr. H.L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Anand, India. ikdrcadl@sancharnet.in
H L
HL
Trivedi
A V
AV
Vanikar
U
U
Thakker
A
A
Firoze
S D
SD
Dave
C N
CN
Patel
J V
JV
Patel
A B
AB
Bhargava
V
V
Shankar
D000273:Adipose Tissue / Q000166:cytology* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology
D006442:Glycated Hemoglobin; D007328:Insulin