Magnetic Resonance Imaging of Transplanted Porcine Neonatal Pancreatic Cell Clusters Labeled with Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles
Jyuhn-Huarng Juang,
Jiun-Jie Wang,
Chia-Rui Shen,
Sung-Han Lin,
Chen-Yi Chen,
Chen-Wei Kao,
Chen-Ling Chen,
Shu-Ting Wu,
Zei-Tsan Tsai,
Yun-Ming Wang
Affiliations
Jyuhn-Huarng Juang
Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Jiun-Jie Wang
Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Chia-Rui Shen
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Sung-Han Lin
Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Chen-Yi Chen
Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Chen-Wei Kao
Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Chen-Ling Chen
Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Shu-Ting Wu
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Zei-Tsan Tsai
Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Yun-Ming Wang
Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan
Recently, we have shown that manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) conjugated with exendin-4 (Ex4) act as a contrast agent that directly trace implanted mouse islet β-cells by magnetic resonance imaging (MRI). Here we further advanced this technology to track implanted porcine neonatal pancreatic cell clusters (NPCCs) containing ducts, endocrine, and exocrine cells. NPCCs from one-day-old neonatal pigs were isolated, cultured for three days, and then incubated overnight with MnMEIO-Ex4 NPs. Binding of NPCCs and MnMEIO-Ex4 NPs was confirmed with Prussian blue staining in vitro prior to the transplantation of 2000 MnMEIO-Ex4 NP-labeled NPCCs beneath the left renal capsule of six nondiabetic nude mice. The 7.0 T MRI on recipients revealed persistent hypointense areas at implantation sites for up to 54 days. The MR signal intensity of the graft on left kidney reduced 62–88% compared to the mirror areas on the contralateral kidney. Histological studies showed colocalization of insulin/iron and SOX9/iron staining in NPCC grafts, indicating that MnMEIO-Ex4 NPs were taken up by mature β-cells and pancreatic progenitors. We conclude that MnMEIO-Ex4 NPs are excellent contrast agents for detecting and long-term monitoring implanted NPCCs by MRI.
