Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin

Transplant Proc. 2008 May;40(4):1135-9. doi: 10.1016/j.transproceed.2008.03.113.

Abstract

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.

Patients and 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.

Conclusion: This report describes safe and effective treatment of insulinopenic diabetics using insulin-producing h-AD-MSC plus CBM without xenogeneic materials.

MeSH terms

  • Adipose Tissue / cytology*
  • Adipose Tissue / physiology
  • Adolescent
  • Adult
  • Bone Marrow Cells / physiology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / surgery*
  • Female
  • Glycated Hemoglobin A / metabolism
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Insulin / biosynthesis*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / physiology

Substances

  • Glycated Hemoglobin A
  • Insulin