Abstract
The ability to deliver cells to appropriate target tissues is a prerequisite for successful cell-based therapy. To optimize cell therapy it is therefore necessary to develop a robust method of in vivo cell delivery quantification. Here we examine Mesenchymal Stem Cells (MSCs) labeled with a series of 4 membrane dyes from which we select the optimal dye combination for pair-wise comparisons of delivery to inflamed tissue in the mouse ear using confocal fluorescence imaging. The use of an optimized dye pair for simultaneous tracking of two cell populations in the same animal enables quantification of a test population that is referenced to an internal control population, thereby eliminating intra-subject variations and variations in injected cell numbers. Consistent results were obtained even when the administered cell number varied by more than an order of magnitude, demonstrating an ability to neutralize one of the largest sources of in vivo experimental error and to greatly reduce the number of cells required to evaluate cell delivery. With this method, we are able to show a small but significant increase in the delivery of cytokine pre-treated MSCs (TNF-α & IFN-γ) compared to control MSCs. Our results suggest future directions for screening cell strategies using our in vivo cell delivery assay, which may be useful to develop methods to maximize cell therapeutic potential.
Highlights
IntroductionVery few clinical applications have been approved so far, which suggests that treatment efficacy could be improved
Cell-based therapeutics offer the potential to address unmet clinical needs in which traditional health care has faltered
mesenchymal stem cells (MSCs) Trafficking to Inflamed Ears To evaluate the performance of lipophilic dyes for use in quantifying cell delivery to an inflamed site, 76104 MSCs stained with each of the range of dyes were systemically infused
Summary
Very few clinical applications have been approved so far, which suggests that treatment efficacy could be improved. One of the primary strategies to improve therapeutic outcome is by increasing delivery of cells to their target tissue. Methods such as alternative culture [7,8], pretreatment with cytokines [9,10,11], transfection [12,13,14], or cell engineering [15,16,17,18] have been used. Our lab has primarily focused on cell surface engineering of therapeutic mesenchymal stem cells (MSCs), and has found that functionalization of the MSC surface can enhance their delivery to an inflamed site in vivo [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
