Changes in the regulation of a circulating organ stem cell in patients with fibrosis or malignant tumors (chondrosarcoma).

ML Labat, PhD,aG Mouthon DMV, PhD b, M Pouchelet PhD c, N Gouhier c, F Escaig b, P Boireau DMV, PhD a, F Quintin-Colonna d

aUMR 956 , Ecole Nationale Veterinaire d'Alfort ENVA, France, b Chimie et Physique Biologiques et Medicales, ENVA, France, c Audiovisuel, INSERM, Le Vesinet, France, dLaboratoire d'Immunologie, ENVA, France

Damage to stem cells have been reported to contribute to neoplasia. Stem cells able to give rise to different cell types circulate in adult human blood as monocytoid cells. They might well represent one single population of pluripotent cells in homeostatic equilibrium with the 'reserve' stem cells buried in the organs. They are normally almost quiescent. Under precise circumstances such as wound healing they may proliferate and migrate in order to participate in the regeneration of the damaged tissue. Indeed such a process has to be tightly controlled. Time-lapse microcinematography shows how a subpopulation of CD4+ T lymphocytes, called phagic T lymphocytes destroy them when they differentiate in vitro. These stem cells which express constitutively HLA-DR molecules are both the activators and the targets of phagic T lymphocytes that penetrate and circulate into them until the stem cells 'explode'. It is a beneficial exception exception to self-tolerance, restricted to normal stem cells, in order to avoid their accumulation out of a repair purpose. In disorders such as fibrosis and chondrosarcoma, these circulating stem cells proliferate, escape destruction by phagic T lymphocytes and accumulate, giving rise in vitro to a 'tissue' evoking the lesion of the patient. The question is raised whether these observations represent early events in the multistep processes leading to fibrosis and/or some malignancies. If so, studying the proliferation of circulating organ stem cells and their behavior in regards to phagic T lymphocytes might constitute a test in terms of predictive oncology.

KEY WORDS: pluripotent organ stem cells, T lymphocytes, exception to self-tolerance.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Stem Cell Biology.