Autografting of bone marrow mesenchymal stem cells alleviates streptozotocin-induced diabetes in miniature pigs: Real-time tracing with MRI in vivo

Abstract

Cellular replacement therapy for diabetes mellitus (DM) has received much attention. In this study, we investigated the effect of transplantation of autologous bone marrow-derived mesenchymal stem cells (ABMSCs) in streptozotocin (STZ)-induced diabetic miniature pigs. Miniature pig BMSCs were cultured, labeled with superparamagnetic iron oxide (SPIO) and transplanted into the pancreas of diabetic miniature pigs through targeted intervention. Blood glucose levels, intravenous and oral glucose tolerance test (OGTT), serum insulin, C-peptide and islets histology were analyzed. These transplanted cells were then identified by magnetic resonance imaging (MRI). The results showed that transplantation of ABMSCs reversed STZ-induced diabetes in miniature pigs. Blood glucose levels, intravenous, OGTT, serum insulin and C-peptide were significantly recovered in the diabetic minipigs with the autologous BMSC (DMAB) transplantation group. In addition, the number of islets was significantly increased in this group compared to the diabetic minipig control (DMC) group with conventional therapy. These data suggested the implantation of autologous BMSCs for type 1 diabetes treatment can partially restore the function of islet β cells and maintain blood glucose homeostasis. Transplanted autologous BMSCs may improve islet repairing by differentiating for new islets and change pancreatic microcirculation and be identified in a real-time manner using MRI in vivo.

Diabetes mellitus and cellular replacement therapy: Expected clinical potential and perspectives

“…Tang et al [53] investigated the effect of transplantation of autologous BMSCs in streptozotocin-induced DM pigs. The results obtained in the animal model have been showed that transplantation of autologous BMSCs may help to reverse a streptozotocin-induced DM.…”

“…Obviously these data suggested that autologous BMSCs implantation might be useful as alternative strategy of DM. Overall, majority investigators have been concluded that the transplantation of BMSCs aimed alternative treatment of DM added to conventional strategy is safe and effective [52,53] .…”

Involvement of autophagy in the procedure of endoplasmic reticulum stress introduced apoptosis in bone marrow mesenchymal stem cells from nonobese diabetic mice

“…Insulin injection, the predominant treatment for T1D, is effective to ameliorate the hyperglycaemia but incompetent to relieve the autoimmunity and to regenerate lost islets. The recent progress in regenerative medicine, especially stem cell therapy, has suggested several novel and potential cures for T1D . Mesenchymal stem cell‐based cell therapy is one of them .…”

Bone Marrow Mesenchymal Stem Cells Alleviate Extracellular Kynurenine Levels, as Detected by High-Performance Liquid Chromatography

“…Additionally, numerous previous studies support the idea that bone marrow mesenchymal stem cells (BMSCs) could be an effective and novel therapy modality for various diseases; e.g., sepsis, endotoxemia, diabetes, lung injury, etc. [3][4][5][6][7][8][9][10][11]. Therefore, our objective was to investigate whether the use of bone marrow mesenchymal stem cells as a new cellular therapy modality could ameliorate kynurenine (KYN) production by endothelial cells in vitro.…”