• Evidence supports the active mechanism of MSC migration towards inflamed or damaged tissues, yet more research to confirm this model is needed and the process of trafficking of MSCs remains not fully understood.

• Infused msCs frequently transmigrate towards damaged regions in significant numbers and have the ability to decrease inflammation and facilitate tissue regeneration.

• The precise MSCs positioning after infusion (localization or tissue-specific transmigration) and MSC phenotype remain vague, making it difficult to confirm mechanisms of MSC engraftment and functional properties.

(3) Direct methods of assessing native MSCs and their trafficking properties is a big unmet need required to conclusively elucidate mechanisms of MSC trafficking during physiological and pathological states. Detection of infused MSCs that remain in an undifferentiated state compared to their differentiated progeny also presents a significant challenge.

(4) Homing of culture-expanded MSCs is inefficient compared to leukocytes and HSCs, which apparently is due to a lack of relevant cell-adhesion and chemokine receptors; however, engineering strategies are available to enhance the homing response. The increased size of MSCs likely promotes passive cell entrapment and reduces the number of MSCs that reach the target site.

As our understanding of the mechanisms of MSC trafficking grows, the ability to enhance homing to specific tissues through engineered approaches should significantly reduce the number of cells required to achieve a therapeutic effect, and presumably provide better outcomes for patients. Accumulating evidence suggests that MSCs have a significantly larger role in regulating wound healing and inflammatory diseases than previously thought. Given the systemic nature of many diseases and the desire to have minimally invasive therapies, systemic infusion of MSCs that can promote tissue regeneration and immunosuppressive effects represents an attractive therapeutic approach. The number of potential therapeutic applications and their efficiency and efficacy will continue to grow as the fundamental biology that is responsible for the MSC regenerative properties and homing responses continues to be elucidated.

Figure 3. Problems Faced in Field of MSC

Trafficking

Given the complexities involved in identifying

MSCs and tracking their position and the lack of

standardized methods for culturing and characterizing

them, new studies in this area should

consider the common problems/challenges that

are experienced and the available methods to

address them.

References

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5. Dominici M. et al., (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 8 (4), p. 315-317.

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7. Bhakta S. Et al., (2005) The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovascular Revascularization Medicine. 7 (1), p. 17-24.

8. Chen L., et al. (2008). Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing. PLoS ONE. 3, (4)

9. Tsai L. et al.,. (2011). Mesenchymal Stem Cells Primed With Valproate and Lithium Robustly Migrate to Infarcted Regions and Facilitate Recovery in a Stroke Model. Stroke. 42, p. 2932-2939

10. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185169/

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