Stem cells for neural regeneration--a potential application of very small embryonic-like stem cells.

There are several clinical situations where stem cells could be employed to recover proper function of central nervous system (CNS). The most important are i) stroke, ii) traumatic brain injury, iii) spinal cord injury and iv) neurodegenerative disorders (Alzheimer’s disease, Parkinsonism, amyotrophic lateral sclerosis and Huntington’s disease). Thus, one of the goals of regenerative medicine is to ameliorate irreversible destruction of brain tissue and spinal cord by harnessing the power of stem cells to initiate neurogenesis in damaged areas of the brain (1-3). The process of neurogenesis supplies new neurons and glial cells (astrocytes and oligodendrocytes) and occurs in the mammalian brain throughout life. Thus far, it has been clearly demonstrated at two locations: in the subventricular zone of the lateral ventricles and olfactory bulb as well as in the subgranular zone of the dentate gyrus in the hippocampus (4-6). Based on frequency and devastating consequences, in adult patients stroke seems as a most important target for developing stem cell therapies (1-3). Stroke is a result of occlusion of a cerebral artery that leads to focal ischemia and ultimately to irreversible damage to neurons and glial cells (7, 8). In case of newborns a leading potential target for stem cell therapies is hypoxic brain damage due to the preterm birth (9). Interestingly, evidence accumulates that it exists an individual sensitivity of brain tissue to hypoxia level both in patients (e.g., premature infants) as well as experimental animals (e.g., CD-1 mice are more resistant as compared to C57BL6 animals) (9). Data from mouse and rat have shown that stroke, hypoxia and the subsequent death of neurons leads to increased proliferation of neural precursors that are located in the subventricular zone, olfactory bulb, and hippocampus (10, 11). Unfortunately, this response is not effective enough to fully restore morphology and function of damaged neural tissue. It is therefore essential to enhance this process by employing i) locally residing stem cells, ii) stem cells that are mobilized in response to stroke and circulate in peripheral blood (PB), or iii) stem cells administered to the patient intravenously or locally that will regenerate damaged brain (1-3). In this review we will focus on stem cell-based strategies aimed at regeneration of neural tissues with a special emphasis on very small embryoniclike stem cells (VSELs) recently discovered by our team. Based on our observation that the number of circulating VSELs in PB increases in mice after experimental stroke (12) as well as in stroke patients (13), we envision that VSELs residing in adult tissues or mobilized into PB could be harnessed in regenerative medicine as a source of adult tissue-derived stem cells for neurogenesis and repair of the CNS. JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2011, 62, 1, 3-12 www.jpp.krakow.pl