Topical delivery of mesenchymal stem cells and their function in wounds

Mesenchymal stem cells are a heterogeneous population of fibroblast-like cells found in most adult organs. However, most of our current knowledge is based on cells of bone marrow or interstitial adipose tissues. These cells are capable of differentiation along various mesenchymal lineages. In addition, they have demonstrated therapeutic characteristics in wounds and ischemic situations. The therapeutic characteristics of these cells are activated upon their entering wounds or other damaged tissues. A current problem is the development of strategies that ensure that these cells reach wound beds in a timely fashion and in sufficient numbers to maximize their therapeutic benefits. Currently, there are two basic delivery methods: systemic infusion of cells into the vascular circulation and direct application of therapeutic cells to wound sites. Skin wounds are optimal candidates for the topical delivery approach. However, the methods by which therapeutic cells are delivered to such wounds vary. This review outlines the basic methods used to deliver therapeutic cells to skin and other wounds. Upon entering wounds, therapeutic cells interact with other wound cells through paracrine mechanisms that are not yet well understood. Nonetheless, interactions with vascular endothelial cells and immunomodulation appear to play significant roles in accelerating wound healing and in reducing scar formation upon the completion of the healing process. Although the phenomenological body of evidence indicating the efficacy of therapeutic cells is substantial, considerable work is still required to better determine the molecular and cellular functions of these cells and to assess their fate and the long-term consequences of their application.