Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

Abstract

Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PDMSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22-1.51) × 10(6)/kg, with an average of 1.35 × 10(6)/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU (P<0.01), and the C-peptide level was increased from 4.1 ±3.7 ng/mL to 5.6 ±3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.

Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation

“…hUC-MSCs from nine hUC samples were isolated as described previously. 4,8 The cells were cultured in a monolayer at 37 1C and 5% CO 2 in DMEM/F12 (Gibco, Grand Island, NY, USA) with 10% fetal calf serum (ExCell Bio, Shanghai, China), harvested using trypsin (Gibco) after reaching 90% confluence, and subplated at a 1 : 3 ratio until reaching a senescence phase. The cell number was counted using Casy-TTC (Roche, Reutlingen, Germany).…”

“…4,5 Cultured hUC-MSCs are being tested in several clinical trials (www.clinicaltrials.gov), and encouraging outcomes have been observed. [6][7][8] Because of the high frequency of genomic mutations during long-term passaging of ESCs and iPSCs, it is necessary to determine whether hUC-MSCs, such as ESCs and iPSCs, can be grown indefinitely in culture and undergo adaptive genetic changes during the long-term expansion.…”

Effects of autologous adipose-derived stem cell infusion on type 2 diabetic rats

“…Pancreatic β-like cells derived from induced-pluripotent stem cells also exhibited a reversal of hyperglycemia in mouse type 2 diabetic models [6]. Clinical trials also demonstrated the effect and safety of stem cell implantation using autologous bone marrow cells or placenta-derived mesenchymal stem cells in patients with type 2 diabetes [7][8][9]. However, most tes mellitus (DM) group were intraperitoneally injected with 35 mg/kg of STZ.…”

Clinical Islet Cell Transplantation – Recent Advances

“…HbA1c levels decreased, less insulin was needed and C-peptide serum levels increased in these patients. In another clinical trial in patients with T2DM, transplantation of placenta-derived mesenchymal stem cells led to increased C-peptide levels as well as a decreased need for insulin 66 . The easy availability of mesenchymal stem cells, the successful early clinical trials, and the promising in vitro and in vivo experiments render these cells a promising candidate for transplantation-based therapies to overcome diabetes.…”