Long-Term/Bioinert Labeling of Rat Mesenchymal Stem Cells with PVA-Gd Conjugates and MRI Monitoring of the Labeled Cell Survival after Intramuscular Transplantation

Abstract

Noninvasive in vivo imaging of transplanted stem cells is an effective method to clarify the mechanisms involved in stem cell transplantation therapy. We labeled rat mesenchymal stem cells (MSCs) with water-soluble magnetic resonance imaging (MRI) contrast agent poly(vinyl alcohol)-gadolinium (PVA-Gd) in order to ascertain the fate of transplanted MSCs in vivo. PVA-Gd was retained and localized in the cytosolic compartment of MSCs for a longer period of time. The effect of PVA-Gd labeling on MSC proliferation was much less than that of the commercially available contrast agent ProHance, and the labeled MSCs were found to have osteoblastic differentiation ability. To study the MSC lifetime in vivo, MSCs were seeded and trapped in the cytocompatible three-dimensional porous scaffolds of Spongel and transplanted. The MRI signal attributed to MSCs was eliminated from the transplanted site in 14 days. Because free PVA-Gd was rapidly eliminated from the site, this signal reduction indicated MSC death in the transplantation site. The low efficiency of MSC transplantation for ischemic tissue may be due to their short lifetime, making it important to develop highly effective stem cell transplantation systems that address cell number, injection position, and cell formulation (suspension, sheet, and aggregates). Our cell survival tracking system would be a very powerful tool to this end and would be applicable in clinical cell therapies.