Use of Magnetocapsules for in Vivo Visualization and Enhanced Survival of Xenogeneic HepG2 Cell Transplants

Cell Medicine

Piotr Walczak¹  Naser Muja¹  Dian R. Arifin¹  Thomas W. Link²  Jeff W.M. Bulte³  Aravind Arepally⁴  Christopher M. Long⁵ 

[1] * Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA§ Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;* Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA† Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA§ Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;* Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA† Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA‡ Department of Chemical and Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA§ Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;¶ Division of Interventional Radiology, Piedmont Hospital, Atlanta, GA, USA# Department of Radiology, The Johns Hopkins Medical Institutes, Baltimore, MD, USA** Department of Surgery, The Johns Hopkins Medical Institutes, Baltimore, MD, USA;† Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

关键词: Cell transplantation;    Fulminant liver failure;    Magnetic resonance imaging;    Iron nanoparticle contrast agent;    Bioluminescent imaging;   

DOI  :  10.3727/215517912X653337

学科分类：生物科学（综合）

来源: Cognizant Communication Corporation

【 摘 要 】

Hepatocyte transplantation is currently being considered as a new paradigm for treatment of fulminant liver failure. Xeno- and allotransplantation studies have shown considerable success, but the long-term survival and immunorejection of engrafted cells need to be further evaluated. Using novel alginate–protamine sulfate–alginate microcapsules, we have coencapsulated luciferase-expressing HepG2 human hepatocytes with superparamagnetic iron oxide nanoparticles to create magnetocapsules that are visible on MRI as discrete hypointensities. Magnetoencapsulated cells survive and secrete albumin for at least 5 weeks in vitro. When transplanted intraperitoneally in immunocompetent mice, encapsulated hepatocytes survive for at least 4 weeks as determined using bioluminescent imaging, which is in stark contrast to naked, unencapsulated hepatocytes that died within several days after transplantation. However, in vivo human albumin secretion did not follow the time course of magnetoencapsulated cell survival, with plasma levels returning to baseline values already at 1 week post-transplantation. The present results demonstrate that encapsulation can dramatically prolong survival of xenotransplanted hepatocytes, leading to sustained albumin secretion with a duration that may be long enough for use as a temporary therapeutic bridge to liver transplantation.

【 授权许可】

CC BY