Figure 4.

Use of humanized mice to study keloid scar development. This schematic diagram illustrates the potential use of humanized mice as hosts for grafting of ESS prepared using keloid-derived or normal skin-derived fibroblasts and keratinocytes. Humanized mice are prepared by injection of CD34+ hematopoietic stem cells into severely immunodeficient mice (see text for details). Resulting mice harbor immune systems reconstituted by human cells, enabling studies of the human immune response in a mouse experimental model. Grafting of ESS containing keloid-derived cells to humanized mice can permit investigation of the role of the immune system in keloid scar development, which is currently not possible using standard immunodeficient mouse hosts. ESS containing normal cells can be compared with ESS containing keloid-derived cells to determine the relative contribution(s) of skin cells and immune cells in keloid pathology. This diagram shows images of ESS prepared using primary keratinocytes and fibroblasts cultured from keloid scar and normal skin. Melanocytes⁶⁹ and microvascular endothelial cells⁷⁰ have also been used in preparation of ESS; thus, this model can be used to study the relative roles of numerous different cell types in keloid pathology. Comparison of mice humanized with keloid patient-derived hematopoietic stem cells versus normal donor stem cells can be used to identify specific components of the immune system involved in keloid development. Currently, isolation of sufficient numbers of hematopoietic stem cells from peripheral blood is an obstacle to implementation of such a model, but future developments aimed at expansion of this population and improved methods for stem cell recovery are expected to enable such studies in the near future. Color images are available online.