Composite Tissue Allotransplantation and Dysregulation in Tissue Repair and Regeneration: A Role for Mesenchymal Stem Cells

Abstract

Vascularized composite tissue allotransplantation is a rapidly evolving area that has brought to the forefront technological advances in the areas of plastic surgery, hand surgery and transplant biology. Composite tissue allografts may have profound functional, aesthetic and psychological benefits, but carry with them the risks of lifelong immune suppression and the inadequate abilities to monitor and prevent rejection. Allografts may suffer from additional insults which prevent regenerative and reparative activities, further weakening their overall benefits. Changes in local blood flow as a consequence of endothelial injury, neuropathy with lack of completely restored neurologic function, infection, inappropriate inflammation with subsequent dysregulated regenerative activity, and paucity of appropriate growth factors may all be involved in reducing the potential of composite tissue allografts and as a consequence, serve as new therapeutic targets to improve composite allograft outcomes. New strategies involving minimized immunosuppression combined with pro-regenerative therapeutics may provide greater inroads in optimizing long-term composite tissue allograft function. One such strategy may include mesenchymal stem cells, which can provide both unique anti-inflammatory and pro-regenerative effects in many tissue types. Insights gained from new studies with mesenchymal stem cells on composite allografts, advances in tissue regeneration reported in other mesenchymal-stem cell based clinical studies, as well as consideration of additional newly described capacities of MSC, may provide new regenerative based strategies for the care of composite tissue allografts.