Magnetic Resonance Imaging of Transplanted Porcine Neonatal Pancreatic Cell Clusters Labeled with Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles

• Published in: Nanomaterials (Basel, Switzerland) Vol. 12; no. 7; p. 1222
• Main Authors: Juang, Jyuhn-Huarng, Wang, Jiun-Jie, Shen, Chia-Rui, Lin, Sung-Han, Chen, Chen-Yi, Kao, Chen-Wei, Chen, Chen-Ling, Wu, Shu-Ting, Tsai, Zei-Tsan, Wang, Yun-Ming
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.04.2022; MDPI
• Subjects: Antibodies; Beta cells; Clusters; Contrast agents; Contrast media; exendin-4-conjugated manganese magnetism-engineered iron oxide nanoparticles; Insulin; Iron oxides; Kidneys; Laboratory animals; Magnetic resonance imaging; Magnetism; Manganese; Nanoparticles; Neonates; Pancreas transplantation; Pancreatic islet transplantation; Pigments; porcine neonatal pancreatic cell clusters; Potassium; Progenitor cells; Sox9 protein; Staining; Stem cells; Swine; Transplantation; Transplants & implants; United States > US; porcine neonatal pancreatic cell clusters; magnetic resonance imaging; exendin-4-conjugated manganese magnetism-engineered iron oxide nanoparticles; transplantation
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano12071222

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.