Abstract

About 43 million individuals in the US currently suffer from disabilities due to arthritis. Cartilage defects are the major source of pain in the affected joints. Current treatments, whilst alleviating some of the clinical symptoms, prove insufficient to cure the underlying irreversible cartilage loss. Stem cells represent a unique source for restoration of cartilage defects. Pre-clinical and clinical trials are currently pursued to investigate the potential of various types of stem cells and stem cell derived chondrocytes to repair arthritic joints. A major challenge with all stem cell-mediated tissue regeneration approaches is death of the transplanted cells with clearance by the immune system. Our current inability to diagnose successful or unsuccessful engraftment of transplanted cells non-invasively in vivo represents a major bottleneck for the development of successful stem cell therapies. A large variety of non-invasive Magnetic Resonance (MR) imaging techniques have been developed over the last decade, which enable sensitive in vivo detection of Matrix Associated Stem Cell Implants (MASI) and early diagnosis of related complications. While initially focused on successfully harvesting cellular MR imaging approaches with easily applicable SuperParamagnetic Iron Oxide Nanoparticles (SPIO), our team began to observe details that will facilitate clinical translation. We therefore started a broader effort to define a comprehensive set of novel, clinically applicable imaging approaches for stem cell transplants in patients. We established immediately clinically applicable nanoparticle labeling techniques for tracking stem cell transplants with MR imaging; we have evaluated the long term MR signal effects of iron oxide nanoparticle labeled MASI in vivo; and we have defined distinct signal characteristics of labeled viable and apoptotic MASI. This review article will provide an overview over these efforts and discuss important implications for clinical translation.

Highlights

  • Arthritis is a major cause of disability, resulting in 992,100 hospitalizations and 44 million outpatient visits in the US each year and causing annual expenses on the order of $95 billion in direct costs and $47 billion in indirect costs

  • Over the last 10 years, we have developed non-invasive Magnetic Resonance (MR) imaging techniques for early detection of complications of the engraftment process of Matrix Associated Stem Cell Transplants (MASI)

  • Our studies have shown that viable and apoptotic MASI demonstrate distinct signal characteristics on MR images, when the cells are labeled with iron oxide nanoparticles [15,36,37,48]

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Summary

Introduction

Arthritis is a major cause of disability, resulting in 992,100 hospitalizations and 44 million outpatient visits in the US each year and causing annual expenses on the order of $95 billion in direct costs (medical treatment) and $47 billion in indirect costs (lost earnings [1,2]). Clinically applicable, cell tracking techniques as a new tool to monitor stem cell engraftment outcomes non-invasively in vivo, we anticipate significantly improving and accelerating the development of successful therapies for cartilage regeneration in patients, and alleviating long term disabilities and related costs to society.

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