Fibroblast heterogeneity - Existence of functionally distinct Thy 1(+) andThy 1(-) human female reproductive tract fibroblasts

Little is known about fibroblasts from the female reproductive tract, much less whether or not functional subsets exist. Fibroblasts are key as sentin el cells for recruiting white blood cells and for wound healing. The purpos e of this research was to evaluate the possibility that functional subsets of fibroblasts exist in the human female reproductive tract. The strategy u sed was to define fibroblast subpopulations based on their surface expressi on of the Thy 1 antigen. In situ staining of human myometrium and endometri um showed heterogeneous staining for Thy 1. Freshly derived strains of fibr oblasts from the myometrium. and endometrium also demonstrated heterogeneou s Thy 1 expression. For the first time, using magnetic heading and fluoresc ence-activated cell sorting, human myometrial fibroblasts were successfully separated into functionally unique Thy 1(+) and Thy 1(-) subsets. Both sub sets produced the proinflammatory cytokines interleukin (IL)-6 and IL-8 aft er IL-1 beta stimulation, but only the Thy 1(+) subset produced MCP-1. Furt hermore, only Thy 1(+) fibroblasts up-regulated CD40 surface expression wit h IL-1 beta or interferon-gamma treatment. Engagement of CD40 in the Thy 1( +) subpopulation induced IL-6, IL-8, and MCP-1. The discovery of functional subsets of reproductive tract fibroblasts now permits assessment of their roles in the normal functions of the reproductive tract and in disease stat es such as adhesions and menorrhagia.