On the track of a human circulating mesenchymal stem cell of neural crest origin

Abstract

The neural markers present in the normal circulating monocytoid cells able, in pathological situations, to trans-differentiate into different mesenchymal-type cells, confirm the hypothesis previously raised that these cells derive from the neural crest. In culture, the normal cells display a great plasticity very reminiscent of microglial cells in culture. Almost a quiescent cell in normal individuals, this monocytoid cell shows its division potentialities in pathological situations of fibrosis and cancer (chondrosarcoma) where it is found to spontaneously proliferate. While the normal neofibroblasts are rapidly recognized and destroyed by fibrophagic T-lymphocytes, the pathological cells escape this control and, as a result, they accumulate in vitro giving rise to a tissue sometimes organized as nodules. Although basically the transdifferentiation process is similar in all the pathological situations of fibrosis and cancer studied so far, the end-result phenotype evokes the pathology the patient is suffering from. It evokes osteoblasts in a case of osteomyelosclerosis, chondroïdocytes in a case of chondrosarcoma, myelofibroblasts in a case of fibrosis of lung and kidney in a patient under ciclosporine treatment. Hence, this circulating monocytoid cell is a multipotent cell with great division potentiality. These are characteristics of stem/preprogenitor cells. Since this circulating monocytoid cell also bears the neural markers we called it a monocytoid ectomesenchymal stem/preprogenitor cell. Therefore, the existence of an ectomesenchymal system is discussed here. The circulating monocytoid ectomesenchymal stem/preprogenitor cell might be involved in the normal cicatrisation process while the fibrophagic T lymphocytes might be involved in its termination. Impairment of this controlled mechanism might result in the development of fibrosis and/or cancer such as chondrosarcoma in vivo. Interestingly, at least in vitro, proliferation is restricted to the monocytoid cell before transdifferentiation takes place. In this model, fibrosis and cancer might share some common steps going from the proliferation of the monocytoid cells to their transdifferentiation into mesenchymal-type cells and the accumulation of these transdifferentiated cells in the tissues. Then, cancer might be distinguished from fibrosis by the additional acquisition of the ability to proliferate by the transdifferentiated cells. The monocytoid ectomesenchymal stem/preprogenitor cell might also be involved in brain neurodegenerative diseases characterized by an accumulation of microglia. The circulating monocytoid ectomesenchymal stem/preprogenitor cell appears as a target for gene therapy in pathological situations of fibrosis and/or cancer where it proliferates out of control. If the normal cell can be expanded and if its transdifferentiation can be directed, the circulating monocytoid ectomesenchymal stem/preprogenitor cell may become a useful tool for cellular therapy, in case of failure in wound healing and tissue regeneration.