Background— Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. Methods and Results— With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. Conclusions— Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

Background and Purpose-In animal models of stroke, functional improvement has been obtained after stem cell transplantation. Successful therapy depends largely on achieving a robust and targeted cell engraftment, with intraarterial (IA) injection being a potentially attractive route of administration. We assessed the suitability of laser Doppler flow (LDF) signal measurements and magnetic resonance (MR) imaging for noninvasive dual monitoring of targeted IA cell delivery. Methods-Transient cerebral ischemia was induced in adult Wistar rats (nϭ25) followed by IA or intravenous (IV) injection of mesenchymal stem cells (MSCs) labeled with superparamagnetic iron oxide. Cell infusion was monitored in real time with transcranial laser Doppler flowmetry while cellular delivery was assessed with MRI in vivo (4.7T) and ex vivo (9.4T). Results-Successful delivery of magnetically labeled MSCs could be readily visualized with MRI after IA but not IV injection. IA stem cell injection during acute stroke resulted in a high variability of cerebral engraftment. The amount of LDF reduction during cell infusion (up to 80%) was found to correlate well with the degree of intracerebral engraftment, with low LDF values being associated with significant morbidity. Key Words: laser Doppler flow Ⅲ MRI Ⅲ stroke Ⅲ stem cells Ⅲ transplantation R ecent discoveries in the field of stem cell research have opened new avenues for the therapy of complex diseases, particularly those of the central nervous system. It has been shown repeatedly in animal models that neurological deficits can be diminished by the introduction of therapeutic cells. 1,2 These observations in animal models provided the basis for the first clinical trials in Parkinson disease 3 and stroke patients. 4 -6 Stroke is a leading cause of serious, long-term disability, and survivors of ischemic insults have little effective treatment available. Although evidence of the beneficial effects of stem cells in animal stroke models is growing, the mechanisms behind the improvements are still unclear. 7 Some investigators have postulated that functional improvement is related to trophic support, which promotes survival of challenged neurons in the penumbra, 8 inducing myelination and neural plasticity, 9 or is attributable to other factors, such as neoangiogenesis. 10 Other researchers suggest that functional improvement is related to both neuronal differentiation and integration. 11 In any case, demonstration of therapeutic effects have been modest to date, and clearly, optimization of robust engraftment and detailed characterization of basic cellular events, such as migration, differentiation, and grafthost interactions, remains essential. Conclusions-HighOne obstacle that has hampered the advancement of stem cell transplantation is inadequate methodology to allow stem cell characterization in living organisms. Several techniques for noninvasive in vivo cellular imaging have been developed, including intravital multi-photon microscopy, 12,13 bioluminescence, 14 PET, 15 and MRI. 1...

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