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  1. 11 Archivum Immunologiae et Therapiae Experimentalis

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  1. 4 Ratajczak M. Z.

  2. 3 Kucia M.

  3. 3 Machalinski B.

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1
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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
|
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
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Defined serum-free culturing conditions for neural tissue engineering of human cord blood stem cells

80%
Ali H., Jurga M., Kurgonaite K., Forraz N., McGuckin C.
Acta Neurobiologiae Experimentalis
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2009
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vol. 69
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issue 1
12-23
EN
Taking tissue engineering applications into clinical trials requires the development of efficient and safe protocols incorporated with effective 3-dimentional cell culturing and differentiation systems in order to develop transplantable tissues that may offer a life-line for patients in the future. Cord blood, which is perhaps the most abundant world stem cell source, has shown previously practical and ethical advantages over other stem cells sources in many research and clinical applications including regenerative medicine. We previously developed a three-step protocol for isolation, expansion and sequential neuronal differentiation of cord blood pluripotent stem cells (characterized with our unique triple immunocytochemisty scheme for Oct-4, Sox-2 and Nanog) in defined serum-free culturing conditions. In this study we incorporated this protocol with 3-dimentional culturing systems which produced artificial neuronal tissues expressing Nestin, NF-200, TUJ1, PSD-95 and NeuN. We showed that cord blood pluripotent stem cells are a potential and promising candidate for future neural tissue engineering and regenerative medicine.
3

Prevalence of human herpesvirus 6 antibodies and DNA in allogeneic stem cell transplant patients: two-year single centre experience

80%
Dzieciatkowski T., Przybylski M., Torosian T., Tomaszewska A., Luczak M.
Archivum Immunologiae et Therapiae Experimentalis
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2008
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vol. 56
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issue 3
201-206
EN
Human herpesvirus 6 (HHV-6) has been recognized as a potentially significant pathogen in hemopoietic stem cell transplant (HSCT) recipients. Different clinical manifestations have been described, including fever, skin rash, bone marrow suppression, and encephalitis. Materials and Methods: A retrospective review of a group of 26 adult recipients of allogeneic HSCTs was conducted. Serum samples taken before transplant were examined for the presence of specific anti-HHV-6 IgM and IgG antibodies. After transplantation, quantitative real-time PCR was used to determine viral load in plasma samples from days 0?180 post-transplant. Results: HHV-6 DNA was detected in plasma samples in 8 (30%) of the 26 recipients between days 18 and 40 after transplantation. All of them developed fever of unknown origin and over 50% had graft-versus-host disease features. Three individuals from this group died during detectable HHV-6 viremia. Another two recipients showed a single positive PCR result at a later time. Infection with HHV-6 was thus confirmed in 10 (38.5%) of the 26 graft recipients. Conclusions: There is a high frequency of detectable HHV-6 viral load in stem cell transplant recipients in Poland. Further investigation to monitor HHV-6 reactivation in graft recipients will be important to improve outcome for these patients.
4
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Embryonic-like stem cells from umbilical cord blood and potential for neural modeling

80%
McGuckin C., Forraz N., Baradez M.-O., Basford C., Dickinson A. M., Navran S., Hartgerink J. D.
Acta Neurobiologiae Experimentalis
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2006
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vol. 66
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issue 4
321-329
EN
Stem cells offer the distinct prospect of changing the face of human medicine. However, although they have potential to form different tissues, are still in the early stages of development as therapeutic interventions. The three most used stem cell sources are umbilical cord blood, bone marrow and human embryos. Whilst, cord blood is now used to treat over 70 disorders, at the time of writing this manuscript, not a single disease has been overcome or ameliorated using human embryonic stem cells. Advancing stem cell medicine requires ethically sound and scientifically robust models to develop tomorrow's medicines. Media attention, however, distracts from this reality; it is important to remember that stem cells are a new visitor to the medical world and require more research. Here we describe the utility of human cord blood to develop neural models that are necessary to take stem cells to the next level ? into human therapies.
5

Predicting outcome in haematological stem cell transplantation

80%
Dickinson A. M., Cavet J., Cullup H., Wang X. N., Jarvis M., Sviland L., Middleton P. G.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
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issue 6
369-376
EN
This present review summarises recent results investigating the role of certain cytokine gene polymorphisms, including TNF, IFN, IL-6, IL-10 and IL1 Ra, in allogeneic stem cell transplantation. The review discusses their role in predicting outcome and the development of a genetic risk index for Graft versus Host Disease in HLA matched sibling transplants. By the comparative use of an in vitro human skin explant model initial results suggest that certain cytokine gene polymorphisms may be associated with more severe disease.
6
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Treatment of lysosomal storage disorders: Focus on the neuronal ceroid-lipofuscinoses

80%
Pierret C., Morrison J. A., Kirk M. D.
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issue 3
429-442
EN
Recent advances in our understanding of lysosomal storage disorders (LSDs) may lead to new therapies to treat the neuronal ceroid-lipofuscinoses (NCLs). In this review, enzyme replacement therapy, gene therapy, cell-mediated therapy and pharmaceutical treatments are considered across the LSDs and extended to therapies for the NCLs. It is likely that a combination of approaches will produce the most beneficial clinical outcome for treatment of pathologies displayed by the NCLs.
7
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Neural commitment of cord blood stem cells (HUCB-NSC/NP): Therapeutic perspectives

80%
Domanska-Janik K., Habich A., Sarnowska A., Janowski M.
Acta Neurobiologiae Experimentalis
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2006
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vol. 66
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issue 4
279-291
EN
Human umbilical cord blood (HUCB) is considered a promising source of neural progenitors capable of being used for cellular therapies in neurological disorders. Here we review briefly our work on the elucidation of mechanisms and development of practical standards as regards the selection, maintenance and use of cord blood derivatives for such purposes. Our results join those of other recent studies in suggesting strongly that, the generation of neural-like cells from tissue belonging to a different germ layer (such as a cord blood is) is most probably explained by reference to a discrete subpopulation of embryonic-like stem cells of pluripotent characteristics. Such cells identified in cord blood through their expression of specific genetic and protein markers can be expanded in vitro and directed toward neurally-committed progenitors differentiating further into more mature neuron-like or macroglia-like cell phenotypes. From this HUCB-derived neural progenitor fraction a novel neural-like stem cell line (HUCB-NSC) has been developed, and characterized in respect of in vitro and in vivo (post-transplantation) properties.
8

Impact of fetal -maternal tolerance in hematopoietic stem cell transplantation

80%
Teshima T., Matsuoka K., Ichinohe T.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 3
165-172
EN
Allogeneic hematopoietic stem cell transplantation (HSCT) is known to cure various hematological disorders; however, its widespread use is limited due to a lack of histocompatible donors. Reciprocal cell traffic between the mother and fetus during pregnancy gives rise to postpartum fetal-maternal lymphohematopoietic microchimerism, which is frequently detected in the blood or tissue of healthy individuals. Studies in clinical and experimental transplantation provide evidence that exposure to non-inherited maternal antigens (NIMAs) during pregnancy may result in long-lasting fetomaternal microchimerism and tolerance induction. Studies of HLA-mismatched HSCT have suggested a relatively lower incidence of severe graft-versus-host disease (GVHD) after transplantation from a NIMA-mismatched donor. Studies using a mouse model have also demonstrated a 'child-to-mother' bone marrow transplantation from an NIMA-exposed donor to reduce the morbidity and mortality of GVHD in an antigen-specific manner while preserving the graft-versus-leukemia effects and favoring the immune reconstitution, thus resulting in a marked improvement in outcome after HSCT. Prospective clinical studies are therefore warranted to confirm these beneficial effects of fetal-maternal tolerance in allogeneic HSCT.
9

Active vaccination after allogeneic bone marrow cell transplantation: a new option in the immunotherapy cancer?

80%
Zoller M., Matzku S.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
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issue 3
197-224
EN
The concept of immunotherapy of cancer has been evoked more than a century ago by W. Coley. Yet, it is only recently that the state of knowledge allows for molecularly defined therapeutic approaches and much effort will still be required to place immunotherapy beside of surgery, chemotherapy and radiation as a forth option. In this review, we will strongly focus on two aspects: active therapeutic vaccination, because it is our belief that this approach will provide a major breakthrough and the potential efficacy of combining active vaccination with allogeneic bone marrow cell transplantation. It lately could be established in clinical trials that allogeneic bone marrow cell transplantation does not require myeloablative conditioning. Only non-myeloabaltive conditioning, which avoids the high toxicity of the conventional approach, allows the recruitment of elderly patients and patients in poor health condition. Concerning active vaccination protocols we will address the questions 1) what the targets (i.e. the antigens) of immunotherapeutic approaches could be; 2) how to achieve an optimal confrontation of the immune system with these tumor-associated antigens; and 3) which response elements are needed for raising a therapeutically successful immune reaction against these. Many question remain to be answered in the field of allogeneic bone marrow transplantation after non-myelablative conditioning to optimize the therapeutic setting for this likely very powerfull tool of cancer therapy. We will briefly summarize current considerations to improve engraftment, to reduce graft versus host disease while strengthening graft versus tumor reactivity. There is some hope that the latter can be 'naturally' maintained during the process of T cell maturation in the allogeneic host. Provided this hypothesis can be substantiated, the efficacy of active vaccination of the allogeneically reconstituted host will meet a pool of virgin T cells, which are tolerant towards the host, but not anergized towards tumor antigens presented by MHC molecules of the host. We only briefly will mention suportive regimen of immunomodulation and those hazards which one is most frequently confronted with in trials to attack tumors with the inherent weapon of immune defense. Though successful immunotherapy of cancer still remains far behind expectation, there is a solid basis to believe that by improving our understanding of molecular mechanisms of immunity, it may become a very powerful and less harmful tool than conventional therapies.
10

No recovery of T-cell receptor excision circles (TRECs) after non-myeloablative allogeneic hematopoietic stem cell transplantation is correlated with the onset of GvHD

80%
Przybylski G. K., Kreuzer K.-A., Siegert W., Schmidt C. A.
Journal of Applied Genetics
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2007
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vol. 48
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issue 4
397-404
EN
Improper T-cell reconstitution with its consequences, graft-vs-host disease (GvHD) and outbreak of viral infections, is the major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). To determine the factors affecting reconstitution of naive T-cells after non-myeloablative HSCT (NM-HSCT), the T-cell receptor excision circle (TREC) content was measured on a weekly basis in 24 transplanted patients with various malignant diseases. We analysed correlations of the results with the development of GvHD. In addition, in 11 chronic myeloid leukaemia (CML) patients, we correlated TREC and BCR-ABL transcript numbers. After HSCT, in most patients (22/24) TRECs became undetectable. In 12 patients, TRECs reappeared 3?4 months after HSCT, in 1 patient TRECs reappeared 5 months after HSCT, and in 11 patients TRECs remained negative for more than a year. All 11 patients who remained TREC-negative, developed acute GvHD grade 2?3, while only 6 out of 13 patients who recovered TRECs developed GvHD. We show that after non-myeloablative HSCT, thymopoiesis takes place and is affected by GvHD. Our results indicate that no recovery of TRECs after NM-HSCT (which most likely reflect the expansion of host-reactive co-transplanted mature T-cells) correlates with the onset of GvHD.
11

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

80%
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.
12

The application of antisense oligodeoxynucleotides strategy in studies on molecular regulation of haematopoiesis

80%
Ratajczak M. Z., Kuczynski W. I.
Biotechnologia
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1995
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issue 1
56-64
EN
In this paper, different aspects of the aplication of antisense strategy in experimental haematology based on own experimental results are discussed.This strategy was succesfullu applied to study role of the : c-kit, STK-1 (FLK2/FLT3), IGF-IR, c-mpl, c-vav and c-myb genes in regulation of human haematopoiesis.
13

Biotechnology in regenerative and reproductive medicine

80%
Kamieniarz K., Nawrot R., Grajek K., Gozdzicka-Jozefiak A.
Biotechnologia
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2006
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issue 2
31-48
EN
Rapid progress in molecular biology, genetics, and mammalian biotechnology has revolutionized diagnostic, therapeutic and reproductive cloning in mammals. Recently, several human gene products have been able to be pharmaceutically explored in transgenic organisms and employed for medical applications. When organs or tissues are irreparably damaged, they may be also replaced with an artificial device or donor organ. Promising and also controversial application for therapeutic and regenerative medicine is stem cells engineering.
14

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

80%
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.
15

Endothelial progenitor cells as a new agent contributing to vascular repair

80%
Miller-Kasprzak E., Jagodzinski P. P.
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2007
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vol. 55
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issue 4
247-259
EN
A special type of stem cells, defined as endothelial progenitor cells (EPCs), has been found in the bone marrow and peripheral blood. These EPCs are incorporated into injured vessels and become mature endothelial cells during re-endothelialization and neovascularization processes. Though a complete phenotypic description of EPCs remains unclear, these cells express several surface markers, the most relevant including CD34 and CD133 antigens. Furthermore, EPCs derived from other sources could also give rise to mature endothelial cells, which makes this group of cells more diverse. The recruitment of EPCs from the bone marrow to homing sites of vasculogenesis is subject to regulation by many factors, including chemokines and growth factors. The precise mechanism of EPC mobilization and differentiation is not entirely elucidated and is still under investigation. Recent studies have suggested that EPCs may promote local angiogenesis by secreting angiogenic growth factors in a paracrine manner. The number and function of EPCs can be affected during pathological conditions, including diabetes mellitus, cardiovascular risk factors for ischemic disease, and graft vasculopathy. Additionally, EPC number and migration capacity could be improved by such factors as drugs, physical exercise, and growth factors. Transplantation of EPCs into ischemic tissues may emerge as a promising approach in the therapy of diseases associated with blood vessel disorders.
16

Developmental potential of mammalian somatic cells

80%
Modlinski J. A., Piliszek A., Karasiewicz J.
Biotechnologia
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2003
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issue 1
9-22
EN
The analysis of the experiments on somatic cloning of mammals reveals that possibly there is a group of cells whose nuclei have greater developmental potential than those of other cells. The group comprises cells of a particular developmental lineage, namely those originating from embryonic mesenchyme and mesoderm. The group remains to be elucidated if somatic cells effectively used for cloning are terminally differentiated, not yet fully differentiated or if they are stem cells. Developmental potential of somatic cell nuclei is best revealed when they are quiescent (i.e. in G0 phase of the cell cycle) upon being introduced into enucleated oocytes. The main obstacle in revealing the potencies of nuclei are the difficulties in their reprogramming before starting embryonic transcription, probably consisting in improper and not fast enough erasing of epigentic modifications of the genome. Developmental plasticity of whole cells as opposed to their nuclei has been experimentally presented in a particular class of somatic cells, namely in stem cells. Stem cells renewing a tissue of their origin can undergo transdifferentiation, that is, in atypical conditions they can differentiate into cells of other tissue and in chimaeras with early embryos - even into many diferent types of cells.
17

Stem cells in nephrology: present status and future

80%
Watorek E., Klinger M.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
|
issue 1
45-50
EN
Stem cell biology is currently developing rapidly because of the potential therapeutic utility of stem cells. The ability to acquire any desired phenotype raises hope for regenerative therapies. Manipulation of these cells is a potentially valuable tool; however, the mechanisms of stem cell differentiation and plasticity are currently beyond our control. In the field of nephrology, the presence of adult kidney stem cells has been debated. Renal adult stem cells may be descendants of some early kidney progenitors or may be derived from bone marrow. Evidence of a hematopoietic stem-cell contribution to renal repair encourages the possibility of bone marrow or stem cell transplantation as a means of treating autoimmune glomerulopathies. The transplantation of fetal kidney tissue containing renal progenitors which then develop into functional nephrons is a step towards renal regeneration. According to recent reports, the development of functional nephrons from human mesenchymal stem cells in rodent whole-embryo culture is possible. Establishing in vitro self organs from autologous stem cells would be a promising therapeutic solution in light of the shortage of allogenic organs and the unresolved problem of chronic allograft rejection.
18
Content available remote

Human cord blood CD34+ cells and behavioral recovery following focal cerebral ischemia in rats

80%
Nystedt J., Makinen S., LaineJ., Jolkkonen J.
Acta Neurobiologiae Experimentalis
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2006
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vol. 66
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issue 4
293-300
EN
The present study investigated effects of human umbilical cord blood derived CD34+ cells on sensorimotor, cognitive, and histological outcome in rats following focal cerebral ischemia. Halothane anesthetized adult male Wistar rats were subjected to transient or permanent occlusion of the middle cerebral artery (MCAO) followed by intravenous administration of CD34+ cells (5 ? 105 or 2 ? 106) after 24 h recovery. The beam-walking and cylinder tests were used to assess sensorimotor function, and Morris water-maze examined cognitive performance during a 25 day follow-up period. Subsequently, rats were perfused for measurement of infarct volumes and detection of CD34+ cells in the brain by immunohistochemistry (MAB1281). MCAO rats showed minor or no spontaneous recovery in sensorimotor function during the follow-up. The recovery profile was similar in MCAO controls and in MCAO rats that received CD34+ cells, although CD34+ cells seemed to improve the use of impaired forelimb. There was also a trend toward improved water-maze performance by CD34+ cells in transient MCAO rats. Infarct volumes assessed from Nissl-stained sections on postoperative day 25 did not differ between the experimental groups. MAB1281-positive cells were not detected in the brain of MCAO rats that received CD34+ cells. The present study suggests that CD34+ cells might improve functional outcome in MCAO rats after systemic administration, but do not significantly provide neuroprotection.
19

Cancer stem cells: the theory and perspectives in cancer therapy

80%
Gil J., Stembalska A., Pesz K. A., Sasiadek M. M.
Journal of Applied Genetics
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2008
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vol. 49
|
issue 2
193-199
EN
The cancer stem cell theory elucidates not only the issue of tumour initiation and development, tumour's ability to metastasise and reoccur, but also the ineffectiveness of conventional cancer therapy. This review examines stem cell properties, such as self-renewal, heterogeneity, and resistance to apoptosis. The ?niche' hypothesis is presented, and mechanisms of division, differentiation, self-renewal and signalling pathway regulation are explained. Epigenetic alterations and mutations of genes responsible for signal transmission may promote the formation of cancer stem cells. We also present the history of development of the cancer stem cell theory and discuss the experiments that led to the discovery and confirmation of the existence of cancer stem cells. Potential clinical applications are also considered, including therapeutic models aimed at selective elimination of cancer stem cells or induction of their proper differentiation.
20

Role of the Wnt/beta-catenin network in regulating hematopoies

71%
Wilusz M., Majka M.
Archivum Immunologiae et Therapiae Experimentalis
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2008
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vol. 56
|
issue 4
257-266
EN
The Wnt/ beta -catenin pathway plays a significant role in several aspects of cell biology, including the stimulation of gene expression, growth, and mobility. Wnt proteins activate at least three cascades: Wnt/ beta-catenin, Wnt/Ca2+, and planar cell polarity. beta-Catenin is not only a very important element of many intracellular signaling pathways, including the Wnt pathway, but it also takes part in creating intercellular adhesive junctions. When overexpressed or mutated it functions as an oncogen. The Wnt/ beta-catenin signaling pathway has been shown to play an important role in controlling the proliferation, survival, and differentiation of hematopoietic cells. Thus any aberrant signaling through this pathway may have a negative influence on hematopoiesis. Indeed, some recent findings suggest that Wnt/beta-catenin signaling is dysregulated in leukemias and lymphomas. All these data position the Wnt/beta-catenin signaling network as a critically important regulator of hematopoiesis and justify future efforts to better understand its role in the process of physiological and pathological hematopoiesis. The present review summarizes recent advances in this field.
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