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The developmental deposition of epiblast/germ cell-line derived cells in various organs as a hypothetical explanation of stem cell plasticity?

100%
Kucia M., Machalinski B., Ratajczak M. Z.
Acta Neurobiologiae Experimentalis
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2006
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vol. 66
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issue 4
331-341
EN
The embryo develops from germ cell line (fertilized oocyte) and precursors of primordial germ cells (PGC) are the first population of stem cells that are specified in mice at the beginning of gastrulation in proximal primitive ectoderm (epiblast) ? region adjacent to the extraembryonic ectoderm. These founder cells subsequently move through the primitive streak and give rise to several extra-embryonic mesodermal lineages and to germ cells. By day 7.25 of embryonic development, a cluster of PGC is visible at the basis of allantois. Subsequently PGC migrate through the embryo proper and colonize genital ridges, where they finally differentiate into sperm and oocytes. We hypothesize that during early development epiblast/germ line-derived cells including PGC become a founder populations of pluripotent stem cells (PSC). These cells are deposited during embryogenesis in various organs and may persist in these locations into adulthood ? for example in bone marrow (BM). To support this, we recently identified in BM a population of very small embryonic-like (VSEL) stem cells that express epiblast/germ line-derived cells transcription factor Oct-4 and several other PGC markers. Similarly, cells expressing Oct-4 were also identified in several adult tissues by other investigators. Thus, pluripotent epiblast/PGC may persist beyond embryogenesis in neonatal and adult tissues. Their fate is defined by several mechanisms which regulate cell proliferation and affect status of somatic imprint on selected genes responsible for pluripotency. We hypothesize that these cells play an important role in tissue/organ regeneration and their presence in adult tissues may explain phenomenon of stem cell plasticity. In pathological situations, however they may undergo malignant transformation and give rise to tumors.
2

Bone-marrow-derived stem cells ? our key to longevity

100%
Ratajczak M. Z., Zuba-Surma E. K., Machalinski B., Kucia M.
Journal of Applied Genetics
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2007
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vol. 48
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issue 4
307-319
EN
Bone marrow (BM) was for many years primarily regarded as the source of hematopoietic stem cells. In this review we discuss current views of the BM stem cell compartment and present data showing that BM contains not only hematopoietic but also heterogeneous non-hematopoietic stem cells. It is likely that similar or overlapping populations of primitive non-hematopoietic stem cells in BM were detected by different investigators using different experimental strategies and hence were assigned different names (e.g., mesenchymal stem cells, multipotent adult progenitor cells, or marrow-isolated adult multilineage inducible cells). However, the search still continues for true pluripotent stem cells in adult BM, which would fulfill the required criteria (e.g. complementation of blastocyst development). Recently our group has identified in BM a population of very small embryonic-like stem cells (VSELs), which express several markers characteristic for pluripotent stem cells and are found during early embryogenesis in the epiblast of the cylinder-stage embryo.
3

The migration of bone marrow-derived non-hematopoietic tissue-committed stem cells is regulated in an SDF-1-, HGF-, and LIF-dependent manner

64%
Kucia M., Wojakowski W., Reca R., Machalinski B., Gozdzik J., Majka M., Baran J., Ratajczak J., Ratajczak M. Z.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 2
121-135
EN
Introduction: Recently we identified in bone marrow (BM) by employing chemotactic isolation to SDF-1 gradient combined with real time RT-PCR analysis a mobile population of CXCR4+ BM mononuclear cells that express mRNA for various markers of early tissue-committed stem cells (TCSCs). In this study we evaluated whether TCSCs respond to other moto-morphogens, such as hepatocyte growth factor (HGF) and leukemia inhibitory factor (LIF). Materials and Methods: We again employed chemotactic isolation combined with real-time RT-PCR analysis to assess whether murine and human BM contain TCSCs that respond to HGF and LIF gradients. We also evaluated expressions of HGF and LIF in damaged organs. Results: We noted that the number of TCSCs is highest in BM from young (1- to 2-month-old) mice and decreases in 1-year-old animals. Murine and human TCSCs 1) respond to HGF and LIF gradients in addition to an SDF-1 gradient, 2) reside in populations of BM-derived non-hematopoietic CD45? cells, and 3) are released (mobilized) from BM into the peripheral blood (PB) during tissue injury (e.g. after partial body irradiation). Conclusions: These findings further support our theory of the BM as a ?hideout' for TCSCs and we suggest that their presence in BM tissue should be considered before experimental evidence is interpreted simply as transdifferentiation/plasticity of hematopoietic stem cells. Since we demonstrated that not only SDF-1, but also HGF and LIF are upregulated in damaged tissues, we postulate that CXCR4+ c-Met+ LIF-R+ TCSC could be mobilized from the BM into the PB, from which they are subsequently chemoattracted to damaged organs, where they play a role in tissue repair/regeneration.
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