Potential involvement of human circulating CD14⁺ monocytes in tissue repair and regeneration

Abstract

Circulating CD14⁺ monocytes originate from hematopietic stem cells and are believed to be committed precursors for phagocytes such as macrophages. Recently, we have reported a primitive human cell population called monocyte-derived multipotential cells (MOMCs), which has a fibroblast-like morphology in culture and a unique phenotype positive for CD14, CD45, CD34, and type I collagen. MOMCs are derived from circulating CD14⁺ monocytes, but circulating precursors still remain undetermined. MOMCs contain progenitors with the capacity to differentiate into a variety of mesenchymal cells in vitro, including bone, cartilage, fat, and skeletal and smooth muscles. Moreover, MOMCs are able to differentiate into the cardiomyogenic and neuronal lineage by co-culturing with primary cultures of embryonic heart and brain, respectively. In addition, MOMCs have capacity of differentiating into endothelium of a mature phenotype with typical morphologic, phenotypic, and functional characteristics. In vitro generation of MOMCs from precursors within circulating monocytes requires their binding to fibronectin and exposure to soluble factors derived from activated platelets. In a rat model of cerebral ischemia, transplantation of MOMCs into the ischemic core results in a significant improvement in neurologic function, but this effect is primarily due to neovascularization through production of a large array of angiogenic factors by MOMCs with some contribution of their differentiation into mature endothelial cells. These findings indicate that circulating CD14⁺ monocytes are involved in a variety of physiologic functions other than innate and acquired immune responses, such as repair and regeneration of the damaged tissue, through a variety of mechanisms.