MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys

Chunlin Zou,Xiahong Teng,Jian Zhang,Fen Huang,Yi Lu,Shuyan Wang,Xin Huang,Guannan Shu,Zhiguo Chen,Yu Alex Zhang,Hongwei Guo,Xiaoting Sun

doi:10.1038/s41598-017-02775-0

Chunlin Zou, Xiahong Teng + Show 10 more

Open Access

https://doi.org/10.1038/s41598-017-02775-0

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Abstract

Insulin-producing cells (IPCs) derived from a patient’s own stem cells offer great potential for autologous transplantation in diabetic patients. However, the limited survival of engrafted cells remains a bottleneck in the application of this strategy. The present study aimed to investigate whether nanoparticle-based magnetic resonance (MR) tracking can be used to detect the loss of grafted stem cell-derived IPCs in a sensitive and timely manner in a diabetic monkey model. Pancreatic progenitor cells (PPCs) were isolated from diabetic monkeys and labeled with superparamagnetic iron oxide nanoparticles (SPIONs). The SPION-labeled cells presented as hypointense signals on MR imaging (MRI). The labeling procedure did not affect the viability or IPC differentiation of PPCs. Importantly, the total area of the hypointense signal caused by SPION-labeled IPCs on liver MRI decreased before the decline in C-peptide levels after autotransplantation. Histological analysis revealed no detectable immune response to the grafts and many surviving insulin- and Prussian blue-positive cell clusters on liver sections at one year post-transplantation. Collectively, this study demonstrates that SPIO nanoparticles can be used to label stem cells for noninvasive, sensitive, longitudinal monitoring of stem cell-derived IPCs in large animal models using a conventional MR imager.

Highlights

Type 1 diabetes (T1D) is a disorder of carbohydrate metabolism characterized by hyperglycemia
To eliminate the possible effect of islet regeneration on blood glucose and insulin levels, fresh pancreatic tissues were obtained from the T1D animals by biopsy 3 months after STZ injection and after euthanasia
Our analysis demonstrated that 1 × 105/ml superparamagnetic iron oxide nanoparticles (SPIONs)-labeled cells resulted in a 70% loss of signal intensity on T2-weighted magnetic resonance imaging (MRI) compared with the control but did not induce any significant change in signal intensity on T1-weighted MRI

Summary

Introduction

Type 1 diabetes (T1D) is a disorder of carbohydrate metabolism characterized by hyperglycemia. A recent primate study by Wang et al demonstrated that SPION-based MRI can detect graft volume reduction prior to any detectable changes in blood glucose after intrahepatic islet allotransplantation[21]. Whether SPION-based MRI monitoring can be applied for the timely detection of graft loss following autologous stem cell-derived IPC transplantation remains unclear. We investigated the feasibility and efficacy of an in vivo MR tracking approach for longitudinally monitoring autologous stem cell-derived IPC grafts using a clinical 1.5-T MRI scanner in a cynomolgus diabetic model. Our data demonstrate that the SPION labeling procedure did not affect the viability or differentiation capacity of adult pancreatic progenitor cells in vitro and that our MRI tracking method can reliably detect IPC graft loss prior to graft dysfunction

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