18F-fluorodeoxyglucose (FDG) also can be taken up and metabolically trapped by the cells and subsequently tracked imaging and analysis, histological verification and clinical outcome measures. security concerns associated with genetic labels and developing methods to follow cell survival, differentiation and integration with host tissue. Imaging may bridge the space between cell therapies and health outcomes by elucidating mechanisms of action through longitudinal monitoring. Introduction Many tissues and organs in the human body, such as the heart, brain and spinal cord, cannot regenerate in response to disease or trauma; damage prospects not to restoration of structure and function but to an inflammatory response and scar formation. Regenerative medicine aims to achieve functional recovery of damaged tissues by providing specific cell populations, alone or incorporated in biomaterial scaffolds, that enhance the bodys intrinsic healing capacity1. The field has seen considerable progress in several areas, including development of new sources of transplantable cells and improved approaches to test the security and efficacy of experimental therapies. However, many difficult difficulties remain. Transplantation into diseased tissues is a nerve-racking experience for cells. Most cells leak out from the injection site or pass away through multiple mechanisms2. The hardy survivors have to migrate, proliferate and self-organize into a tissue, integrate functionally with the host parenchyma and recruit a vascular supply to support their long-term survival and function. Transplanted cells are often immature and are required to mature stability of 111In-oxine provides the option to acquire images after 24 h or more, whereas 99mTc chelated brokers have a relatively short half-life (6 h). 18F-fluorodeoxyglucose (FDG) also can be taken up and metabolically caught by the cells and subsequently tracked imaging and analysis, histological verification and clinical outcome measures. Document all results and do not deviate from standard operating procedures once established. imagingEnsure that labeled cells are detectable with high sensitivity and specificity using clinical scanners. Understanding the number of cells/voxel that migrate to targeted regions is usually important in determining preclinical doses, schedules and administration routes. It is impossible and unnecessary to track single cells. Scale upThe ability to move a labeling technique from your bench to a clinical Good Manufacturing Practice facility may be difficult, but it is essential for producing large numbers of cells for clinical trials. Phase 1 trials that include dose escalation should also be used to determine delivery methods, safety, toxicity and AZ-960 maximum tolerated dose of the labeled cells. Box 4 Recommendations for preclinical evaluation of imaging methods If imaging is to be used in a cell-therapy clinical trial, it is necessary to compile appropriate data for presentation during pre-IND discussions with the regulatory agency. These data should include the following. assessments of direct or indirect labeling methods should be compared to unlabeled cells and include determination of labeling efficiency; label concentration; rate of cell death; short and longer-term proliferation capacity; differentiation capacity; migration capacity; immunogenicity in a mixed lymphocyte reaction; and surface markers. It is important to document that labeling does not switch cell potency. For cells whose function is usually secretory, potency can be defined as hormone, neurotransmitter, cytokine/chemokine or growth factor release. For mechanically active cells, such as cardiomyocytes, potency includes electrical and mechanical activity. Gene expression profiling has not been required or routinely recommended to evaluate direct labeling methods because of potential variability between FSHR donor cells and uncertainty in how these data correlate with potency. For indirect labels, it may AZ-960 be necessary AZ-960 to AZ-960 determine the chromosomal location of the label to avoid proximity to oncogenes. If a suicide or therapeutic gene is inserted with the reporter gene, expression of both genes must be documented, along with efficacy of the suicide gene. Long-term passaging of cells is needed to ensure stability of.