Mesenchymal stem cells (MSCs) are currently being widely investigated both in the lab and in clinical trials for multiple disease states. The differentiation, trophic, and immunomodulatory characteristics of MSCs contribute to their therapeutic effects. Another often overlooked factor related to efficacy is the degree of engraftment. When reported, engraftment is generally low and transient in nature. MSC delivery methods should be tailored to the lesion being treated, which may be local or systemic, and customized to the mechanism of action of the MSCs, which can also be local or systemic. Engraftment efficiency is enhanced by using intra-arterial delivery instead of intravenous delivery, thus avoiding the “first-pass” accumulation of MSCs in the lung. Several methodologies to target MSCs to specific organs are being developed. These cell targeting methodologies focus on the modification of cell surface molecules through chemical, genetic, and coating techniques to promote selective adherence to particular organs or tissues. Future improvements in targeting and delivery methodologies to improve engraftment are expected to improve therapeutic results, extend the duration of efficacy, and reduce the effective (MSC) therapeutic dose. 1. Introduction Mesenchymal stem cells (MSCs) are multipotential adult progenitor cells that have the capacity to differentiate along several mesenchymal lineages, including cartilage, adipose, marrow stroma, and bone tissue [1–3]. Studies have been conducted on the use of MSCs as a therapeutic based on this capacity to differentiate directly into these end-stage phenotypes, including the use of MSCs to promote or augment bone repair [4] and for the repair of cartilage defects [4, 5]. In addition to direct differentiation into end-stage phenotypes, MSCs have also been shown to have a positive therapeutic effect in many repair situations because of their capacity to secrete trophic factors (reviewed in [6]) that contribute to repair via the promotion of vascularization and the inhibition of cell death as well as through the modulation of the immune response. Currently, there are over 160 open studies and 116 closed clinical trials (results retrieved (3rd June 2013) in a search of www.clinicaltrials.gov on the search term “mesenchymal stem cells” and excluding trials with an unknown status and those that were conducted in vitro) that use MSCs to treat a variety of conditions that range from direct formation of bone tissue to treatments for graft versus host disease (GvHD) [7–9], myocardial infarction, brain trauma, and multiple
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