Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells
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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 × 104 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.
KeywordsInsulin-secreting cells Adipose tissue Mesenchymal stem cells Hematopoietic stem cells Insulin-dependent diabetes mellitus
Cultured bone marrow
Fasting blood sugar levels
Glutamic acid decarboxylase
Hematopoietic stem cells
Mesenchymal stem cells
Postprandial blood sugar level
Insulin-dependent diabetes mellitus
The authors thank the staff and technicians of IKDRC-ITS, India, for all the technical help. The authors also thank Shobhana Sengunthar for providing statistical analysis.
Conflict of interest
- 6.Vanikar AV, Dave SD, Thakkar UG, Trivedi HL (2010) Co-transplantation of adipose tissue-derived insulin-secreting mesenchymal stem cells and hematopoietic stem cells: a novel therapy for insulin-dependent diabetes mellitus. Stem Cells Int Article ID 582382 5 pagesGoogle Scholar