228 research outputs found
Stem cells and their potential use in a clinic
Thanks to the progres in science the man of the beginnings of the third millenium
uses the technologies which have been reserved for the highest entities.
The development of physics has resulted in discovering many mysteries
of nuclear physics and the development of biology and genetics has enriched
man’s knowledge of the origins of living organisms and their regeneration. As
a result, mankind has been introduced in the fascinating world of stem cells.Pomorski Uniwersytet Medyczny w Szczecini
Cancer stem cells - normal stem cells "Jedi" that went over to the "dark side"
Evidence has accumulated that cancer develops from a population of quiescent tissue committed/pluripotent stem
cells (TCSC/PSC) or cells developmentally closely related to them that are distributed in various organs. To support this notion,
stem cells (SC) are long lived cells and thus may become the subject of accumulating mutations that are crucial for
initiation/progression of cancer. More important, they may maintain these mutations and pass them to the daughter stem cells.
Therefore, mutations that occur in normal SC, accumulate during the life of an organism at the clonal level in the stem cell
compartment committed to a given tissue/organ. As a consequence, this may lead to the malignant transformation of SC and
tumor initiation. Furthermore, many biological features of normal and cancer SC such as the physiological trafficking of normal
and metastasis of cancer stem cells involve similar molecular mechanisms, and we discuss these similarities here. Therefore,
looking both at the origin and behavioral aspects we can envision cancer SC being normal SC "Jedi" that went over to the "dark
side"
The Expanding Family of Bone Marrow Homing Factors for Hematopoietic Stem Cells: Stromal Derived Factor 1 Is Not the Only Player in the Game
The α-chemokine stromal derived factor 1 (SDF-1), which binds to the CXCR4 and CXCR7 receptors, directs migration and homing of CXCR4+ hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) and plays a crucial role in retention of these cells in stem cell niches. However, this unique role of SDF-1 has been recently challenged by several observations supporting SDF-1-CXCR4-independent BM homing. Specifically, it has been demonstrated that HSPCs respond robustly to some bioactive lipids, such as sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), and migrate in response to gradients of certain extracellular nucleotides, including uridine triphosphate (UTP) and adenosine triphosphate (ATP). Moreover, the responsiveness of HSPCs to an SDF-1 gradient is enhanced by some elements of innate immunity (e.g., C3 complement cascade cleavage fragments and antimicrobial cationic peptides, such as cathelicidin/LL-37 or β2-defensin) as well as prostaglandin E2 (PGE2). Since all these factors are upregulated in BM after myeloblative conditioning for transplantation, a more complex picture of homing emerges that involves several factors supporting, and in some situations even replacing, the SDF-1-CXCR4 axis
Very Small Embryonic/Epiblast-Like Stem Cells (VSELs) Residing in Adult Tissues and Their Role in Tissue Rejuvenation and Regeneration
Heterogeneous populations of bone marrow stem cells--are we spotting on the same cells from the different angles?
Accumulated evidence suggests that in addition to hematopoietic stem cells (HSC), bone marrow (BM) also harbors endothelial stem cells (ESC), mesenchymal stem cells (MSC), multipotential adult progenitor cells (MAPC), pluripotent stem cells (PCS) as well as tissue committed stem cells (TCSC) recently identified by us. In this review we discuss the similarities and differences between these cell populations. Furthermore, we will present the hypothesis that all of these versatile BM derived stem cells are in fact different subpopulations of TCSC. These cells accumulate in bone marrow during ontogenesis and being a mobile population of cells are released from BM into peripheral blood after tissue injury to regenerate damaged organs. Furthermore, since BM is a "hideout" for TCSC, their presence in preparations of bone marrow derived mononuclear cells should be considered before experimental evidence is interpreted simply as trans-differentiation or plasticity of HSC. Finally, our observation that the number of TCSC accumulate in the bone marrow of young animals and their numbers decrease during senescence provides a new insight into aging and may explain why the regeneration processes becomes less effective in older individuals
Heterogeneous populations of bone marrow stem cells : are we spotting on the same cells from the different angles?
Accumulated evidence suggests that in addition to hematopoietic stem cells (HSC), bone marrow (BM) also harbors endothelial stem cells (ESC), mesenchymal stem cells (MSC), multipotential adult progenitor cells (MAPC), pluripotent stem cells (PCS) as well as tissue committed stem cells (TCSC) recently identified by us. In this review we discuss the similarities and differences between these cell populations. Furthermore, we will present the hypothesis that all of these versatile BM derived stem cells are in fact different subpopulations of TCSC. These cells accumulate in bone marrow during ontogenesis and being a mobile population of cells are released from BM into peripheral blood after tissue injury to regenerate damaged organs. Furthermore, since BM is a "hideout" for TCSC, their presence in preparations of bone marrow derived mononuclear cells should be considered before experimental evidence is interpreted simply as trans-differentiation or plasticity of HSC. Finally, our observation that the number of TCSC accumulate in the bone marrow of young animals and their numbers decrease during senescence provides a new insight into aging and may explain why the regeneration processes becomes less effective in older individuals
Mobilization of Hematopoietic Stem Cells as a Result of Innate Immunity-Mediated Sterile Inflammation in the Bone Marrow Microenvironment—The Involvement of Extracellular Nucleotides and Purinergic Signaling
Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic enzymes. All these factors together trigger activation of the complement and coagulation cascades, both of which orchestrate egress of HSPCs into BM sinusoids and lymphatics. Recent evidence also indicates that, in addition to attenuation of the SDF-1–CXCR4 and VLA-4–VCAM-1 retention axes in the BM microenvironment and the presence of a mobilization-directing phosphosphingolipid gradient in PB, an important role in the mobilization process is played by extracellular nucleotides and purinergic signaling. In particular, a new finding by our laboratory is that, while extracellular ATP promotes mobilization of HSPCs, its derivative, adenosine, has the opposite (inhibitory) effect
Stem cell biology : a never ending quest for understanding
Stem cells (SC) research is an important part of biotechnology that could lead to the development of new therapeutic strategies. A lot of effort has been put to understand biology of the stem cells and to find genes and subsequently proteins that are responsible for their proliferation, self-renewal and differentiation. Different cytokines and growth factors has been used to expand stem cells, but no combination of these factors was identified that could effectively expand the most primitive stem cells. Recently, however, genes and receptors responsible for SC proliferation and differentiation have been described. Ligands for these receptors or these genes themselves are being already used for ex vivo expansion of stem cells and the first data are very promising. New markers, such as CXCR4 and CD133, have been discovered and shown to be present on surface of hematopoietic stem cells. The same markers were recently also found to be expressed on neuronal-, hepatic- or skeletal muscle-stem cells. By employing these markers several laboratories are trying to isolate stem cells for potential clinical use. New characteristics of stem cells such as transdifferentiation and cell fusion have been described. Our team has identified a population of tissue committed stem cells (TCSC). These cells are present in a bone marrow and in other tissues and they can differentiate into several cell types including cardiac, neural and liver cells
Hormon wzrostu a proces starzenia się
Studies in mutant, gene knock-out and transgenic mice have demonstrated that growth hormone (GH) signalling has a major impact on
ageing and longevity. Growth hormone-resistant and GH-deficient animals live much longer than their normal siblings, while transgenic
mice overexpressing GH are short lived. Actions of GH in juvenile animals appear to be particularly important for life extension and
responsible for various phenotypic characteristics of long-lived hypopituitary mutants.
Available evidence indicates that reduced GH signalling is linked to extended longevity by multiple interacting mechanisms including
increased stress resistance, reduced growth, altered profiles of cytokines produced by the adipose tissue, and various metabolic adjustments
such as enhanced insulin sensitivity, increased oxygen consumption (VO2/g) and reduced respiratory quotient. The effects of removing
visceral fat indicate that increased levels of adiponectin and reduced levels of pro-inflammatory cytokines in GH-resistant mice are
responsible for their increased insulin sensitivity. Increased VO2 apparently represents increased energy expenditure for thermogenesis,
because VO2 of mutant and normal mice does not differ at thermoneutral temperature. Recent studies identified GH- and IGF-1-dependent
maintenance of bone marrow populations of very small embryonic-like stem cells (VSELs) as another likely mechanism of delayed ageing
and increased longevity of GH-deficient and GH-resistant animals.
Many of the physiological characteristics of long-lived, GH-related mouse mutants are shared by exceptionally long-lived people and by
individuals genetically predisposed to longevity.W badaniach na zmutowanych i transgenicznych myszach wykazano, że przekazywanie sygnałów przez hormon wzrostu (GH) wywiera
istotny wpływ na procesy starzenia się organizmu i długowieczność. Zwierzęta, u których stwierdza się oporność na hormon wzrostu
lub jego niedobór, żyją dłużej niż ich normalne rodzeństwo, podczas gdy myszy transgeniczne wykazujące nadekspresję GH żyją krótko.
Działania, jakie wywiera GH u młodocianych zwierząt wydają się odgrywać szczególnie ważną rolę w wydłużaniu życia i są odpowiedzialne
za różnorodne cechy fenotypowe długowiecznych mutantów z niedoczynnością przysadki.
Z dostępnych dowodów naukowych wynika, że osłabione przekazywanie sygnałów przez GH wiąże się ze zwiększeniem długowieczności,
u podstawy czego leży wiele współzależnych mechanizmów obejmujących zwiększoną odporność na stres, osłabione wzrastanie, zmieniony
profil cytokin wytwarzanych przez tkankę tłuszczową, a także różne adaptacje metaboliczne, np. zwiększona insulinowrażliwość,
zwiększone zużycie tlenu (VO2/g) i zmniejszony współczynnik oddechowy. Konsekwencje usunięcia trzewnej tkanki tłuszczowej wskazują,
i że zwiększoną insulinowrażliwość u myszy opornych na GH odpowiedzialne jest zwiększone stężenie adyponektyny i zmniejszone
stężenie cytokin prozapalnych. Zwiększone VO2 wydaje się wynikać ze zwiększenia wydatkowania energii na termogenezę, bowiem
w temperaturze termoneutralnej VO2 u myszy zmutowanych i myszy niezmutowanych nie różni się. W najnowszych badaniach — jako
kolejny prawdopodobny mechanizm opóźnionego starzenia się organizmu i zwiększonej długowieczności u zwierząt z niedoborem GH
i opornością na GH — zidentyfikowano zależne od GH i IGF1 podtrzymywanie szpikowych populacji bardzo małych komórek macierzystych
podobnych do zarodkowych (VSEL, very small embryonic-like stem cells).
Wiele z cech fizjologicznych długowiecznych myszy z mutacjami związanymi z GH występuje też u bardzo długo żyjących ludzi i osób
genetycznie predysponowanych do długowieczności
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