title: Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells.
abstract: Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually resulting from autoimmune-mediated β-cell destruction requiring lifetime exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising therapy. We present our experience of treating IDDM with co-infusion of in vitro autologous adipose tissue-derived MSC-differentiated insulin-secreting cells (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent from ten patients. ISC were differentiated from autologous adipose tissue-derived MSC and were infused with bone marrow-derived HSC in portal, thymic circulation by mini-laparotomy and in subcutaneous circulation. Patients were monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 × 10(4) cells/μL were infused. No untoward effects were observed. Over a mean follow-up of 31.71 months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of 0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99 to 6.72%. Mean GAD antibodies were positive in all patients with mean of 331.10 IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with HSC represents a viable novel therapeutic option for IDDM.
authors: Stem Cell Lab, Transplantation Biology Research Centre, Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre (IKDRC)-Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), Civil Hospital Campus, Asarwa, Ahmedabad, 380016, Gujarat, India, shrutiddave@yahoo.com.
authors: S D
authors: SD
authors: Dave
authors: A V
authors: AV
authors: Vanikar
authors: H L
authors: HL
authors: Trivedi
authors: U G
authors: UG
authors: Thakkar
authors: S C
authors: SC
authors: Gopal
authors: T
authors: T
authors: Chandra
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000819:agonists / Q000097:blood; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology / Q000628:therapy*; D005260:Female; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D014182:Transplantation, Autologous
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007328:Insulin