D.A. Kedziorek

Superparamagnetic iron oxide labeling of stem cells for MRI tracking and delivery in cardiovascular disease.

In the mid-1980s, iron oxide nanoparticles were developed as contrast agents for diagnostic imaging. In the last two decades, established methods to label cells with superparamagnetic iron oxides (SPIOs) have been developed to aid in targeted delivery and tracking of stem cell therapies. The surge in cellular therapy clinical trials for cardiovascular applications has seen a similar rise in the number of preclinical animal studies of SPIO-labeled stem cells in an effort to understand the mechanisms of cardiovascular regenerative therapy and stem cell biodistribution. The adoption of a limited number of methods of direct labeling of stem cells with SPIOs is due in large part to the desire to rapidly translate these techniques to clinical trials. In this review, we will outline the most commonly adopted methods for iron oxide labeling of stem cells for cardiovascular applications and describe strategies for magnetic resonance imaging (MRI) of magnetically labeled cells in the heart.

Recent developments and future challenges on imaging for stem cell research.

As clinical trials with stem cells for cardiac regenerative therapy move forward, advances in imaging equipment and technique offer powerful methods to evaluate therapeutic efficacy. Methodologies to label stem cells for tracking continue to expand. Non-invasive imaging offers the potential to better understand the interaction of exogenous stem cells with the host to answer questions such as the best cell type(s), timing of delivery, dose, and delivery route. If successful, these techniques may enable individually tailored dosing of stem cell therapeutics. However, techniques that are suitable for animal models of cardiac disease may have hurdles to clinical translation beyond simple biocompatibility issues. Challenges include the high cost of advanced imaging techniques, applicability in acute ischemic disease, and regulatory approval. In this review, we will cover some new imaging techniques and labeling strategies and assess the obstacles to clinical adoption.

MRI and CT tracking of mesenchymal stem cells with novel perfluorinated alginate microcapsules

Background and objectives Stem cell therapies, although promising for treating ischemic arterial diseases, suffer from poor engraftment and the inability to noninvasively monitor and track transplanted cells in vivo. Stem cell microencapsulation in conjunction with an imaging contrast agent provides a means to prevent cell immunorejection and enable cell tracking with appropriate imaging modalities. The objective of this study was to design and evaluate a novel MRIand CT-visible, immunoprotectable alginate microcapsule containing an imaging contrast agent, perfluorooctylbromide (PFOB), for mesenchymal stem cell (MSC) delivery.

Erratum to Walczak et al. Applicability and limitations of MR tracking of neural stem cells with asymmetric cell division and rapid turnover: The case of the shiverer dysmyelinated mouse brain. Magn Reson Med 2007;58:261–269.

*Correspondence to: Dr. Jeff W. M. Bulte, Ph.D., Russell H. Morgan Department of Radiology and Radiological Science, Department of Chemical and Biomolecular Engineering, Cellular Imaging Section and Vascular Program, and Institute for Cell Engineering, Johns Hopkins University School of Medicine, 217 Traylor Building, 720 Rutland Ave, Baltimore, MD 21205-2195. E-mail: jwmbulte@mri.jhu.edu Received 15 August 2007; revised 15 August 2007; accepted 20 August 2007. DOI 10.1002/mrm.21412 Published online in Wiley InterScience (www.interscience.wiley.com). Figure 8. Scheme of symmetric vs. asymmetric cell division and dilution of Feridex particles. a: In symmetrically dividing cells, the contrast agent is distributed equally among daughter cells. b: Asymmetric cell division, as commonly encountered in stem cells, leads to an unequal distribution of Feridex particles. This, in turn, can lead to a sharp decline in cell detectability. In this hypothetical example, cells without particles are MR-invisible (solid crosses), while cells with only one particle are borderline detectable (dashed crosses). The asterisk denotes a parent cell that undergoes self-renewal with an exact copy of itself, which is a hallmark feature of undifferentiated, noncommitted stem cells.

PET-MRI tracking of imaging-visible microencapsulated stem cells in immunocompetent rabbits

Background Exogenous stem cell therapy has shown benefits for treating peripheral arterial disease patients, who are not amenable for conventional revascularization therapy. Previously, we have demonstrated the ability of imaging-visible cell microencapsulation to overcome the challenges of poor cell retention/survival and difficulties with monitoring cell delivery success. However, in vivo cell viability cannot be assessed noninvasively. Here, we investigate the potential of PET-MRI tracking of F MRI-visible microencapsulated human mesenchymal stem cells (hMSCs) labeled with triple-fusion (TF) reporter gene in non-immunosuppressed rabbits.

A comparison of time-of-flight mr angiography, contrast-enhanced mr angiography and ct angiography to evaluate vessel area in a rabbit peripheral arterial disease model

Inducing arteriogenesis using stem cells is a promising treatment for patients suffering from peripheral arterial disease (PAD). Computed tomography angiography (CTA) is often used as a gold standard method for evaluating vessel diameters in ischemic tissue after therapy.