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.

Mesenchymal stem cells in obesity: insights for translational applications

“…For example, MSCs can differentiate into insulin-producing cells, suggesting MSCs as a source of transplantation material in the treatment of diabetes, [72][73][74] while other studies demonstrated the angiogenic and anti-inflammatory potential of MSCs in supporting islet transplantation. 75,76 Furthermore, Dave et al 77 reported a clinical trial showing that co-infusion of in vitro-generated insulin-producing cells differentiated from autologous adipose-derived MSCs and bone marrow-derived hematopoietic stem cells into the portal circulation, thymus, and subcutaneous tissue increased serum C-peptide levels and improved glycosylated hemoglobin levels. Significant progress has thus been made in the field of MSC and diabetes, and further research is warranted to realize the clinical potential of MSC adipogenesis in this area.…”

Adipose-derived mesenchymal stem cells improve glucose homeostasis in high-fat diet-induced obese mice

“…In patients with type 1 diabetes, co-transplantation of ASC-derived insulin-secreting islets with hematopoietic stem cells decreased exogenous insulin requirement, increased c-peptide levels, and prevented ketoacidosis [ 26 ]. In another clinical trial in the same patient population, transplantation of ASC-derived insulin + cells improved patients’ HB1Ac levels, and decreased serum GAD antibody, without causing adverse effects [ 27 ].…”

Stem cells in the treatment of diabetes mellitus — Focus on mesenchymal stem cells

“…Moreover, MSC are immune-privileged because they express very low levels of major histocompatibility complex (MHC) class I and no MHC class II which normally prevents or strongly reduces immune responses [172,173]. In clinical use since 1995 [56], MSC are considered clinically safe [106] and both administration of autologous and also allogenic MHC-mismatched MSC is generally well tolerated and clinically effective [174][175][176].…”