The role of resident monocytes and vascular pericytes in the stem cell niche and regenerative medicine

The perivascular tissue-specific stem cell niche (SCN) determines nuclear reprogramming of multipotent stem cells into particular cell types in distinct tissues in vivo. It represents a morphostatic (homeostatic) mechanism executed by the so-called tissue control system (TCS), which is associated with postcapillary venules and consists of vascular pericytes regulated by the autonomic nervous system and of resident perivascular monocytederived cells. Tissue morphostasis executed by the TCS is a complex procedure consisting of three processes: i) Stem cell and tissue renewal by asymmetric division of stem cells, ii) Preservation of tissue cells in a properly differentiated (functional) state, and iii) Maintenance of tissue quantity. The TCSmediated functional preservation of tissuespecific cells is established during the morphogenetic critical developmental period, such as developmental immune adaptation, as a stop effect at the level of resident self-renewing tissue monocyte-derived cells (MDC), and its function declines with advancing age. The functional stop effect differs between the tissues, and an inhibition or acceleration of tissue differentiation during the critical developmental period can result in persistent functional immaturity or premature tissue aging. In addition, a retardation of tissue development can cause an earlier failure of that tissue function, like a premature ovarian failure. A promising approach in regenerative medicine is a chemical approach, such as the combination of sex steroids stimulating growth of endogenous stem cells for neuronal, vascular, and cardiac repair. Sex steroid combinations and doses for clinical applications are suggested. Regenerative medicine may be more successful in acute/traumatic disorders with intact morphostatic SCN compared to the chronic and degenerative diseases caused by an altered SCN. If we attain the capacity to repair the function of altered SCN and the tissue- specific stop effect by trascriptional therapy, we may be able to provide novel treatments for early postnatal tissue disorders, improve regenerative medicine, and delay aging.