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Bone marrow (BM) contains a population of self-renewing hematopoietic stem cells (HSC) that give rise to cells from all hemato-lymphopoietic lineages. The concept that HSC could also be plastic and be able to transdifferentiate into stem/progenitor cells for different non-hematopoietic tissues became one of the most controversial issues of modern stem cell biology. Accumulating experimental evidence suggests that contribution of BM-derived stem cells to organ/tissue regeneration could be explained not by plasticity (transdifferentiation) of HSC but rather by the presence of non-hematopoietic stem cells in BM. In this review new evidence will be presented, that adult BM contains a small population of pluripotent very small embryonic-like (VSEL) stem cells. These cells are deposited in BM early during ontogenesis and could be mobilized from BM and circulate in peripheral blood during tissue/organ injury in an attempt to regenerate damaged organs. However, if these cells are mobilized at the wrong time and migrate to the wrong place they may contribute to the development of several pathologies, including tumor formation.
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Stem cells and their outstanding concerns

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Stem cells have captured considerable scientific and clinic interest because of their potential to renew themselves and to differentiate into one or more adult cell types. Thus stem cells have been recognized as a potential tool for the development of innovative therapeutic strategies in different disease disorders. Stem cells can be discriminating based on their differentiated potential as totipotent, pluripotent, multipotent or unipotent cells. There are in general three types of stem cells: embryonic, fetal and adult stem cells. While embryonic stem cell therapy has a lot of ethical concerns due to their obtaining but also unlimited proliferation and uncontrolled differentiation, fetal and adult stem cells have been used in the treatment of different diseases. The bone marrow, peripheral blood and umbilical cord blood are ideal sources of adult stem cells because there are easily accessible and contain two types of stem cells: hematopoietic stem cells giving rise to all blood cell types and mesenchymal stem cells differentiating into cells of mesodermal lineage. This review describes the general characteristics of these stem cell populations and their current applications in regenerative medicine. Additionally induced pluripotent stem cells generated through the reprogramming of differentiated adult cells are described.
The goal of regenerative medicine is to ameliorate irreversible destruction of brain tissue by harnessing the power of stem cells in the process of neurogenesis. Several types of stem cells, including mesenchymal stem cells, hematopoietic stem cells, as well as neural cells differentiated from embryonic stem cell lines, have been proposed as potential therapeutic vehicles. In this review paper we will discuss a perspective of stem cell therapies for neurological disorders with special emphasis on potential application of cells isolated from adult tissues. In support of this our group found that murine bone marrow contains a mobile population of Oct-4+CXCR4+SSEA-1+Sca-1+lin–CD45– very small embryonic-like stem cells (VSELs) that are mobilized into peripheral blood in a murine stroke model. The number of these cells in circulation increases also after pharmacological mobilization by administration of granulocyte colony stimulating factor (G-CSF). Recently we found that VSELs are present in various non-hematopoietic adult organs and, interestingly, our data indicate that the brain contains a high number of cells that display the VSEL phenotype. Based on our published data both in human and mice we postulate that VSELs are a mobile population of epiblast/germ line-derived stem cells and play an important role as an organ-residing reserve population of pluripotent stem cells that give rise to stem cells committed to particular organs and tissues - including neural tissue. In conclusion human VSELs could be potentially harnessed in regenerative medicine as a source of stem cells for neurogenesis.
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