DigitalUM :: Browsing by Subject "Stem cell"

Browsing by Subject "Stem cell"

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Open Access
Adult stem and transit-amplifying cell location
(Murcia : F. Hernández, 2006) Díaz-Flores Jr., L.; Madrid, J.F.; Gutiérrez, Ricardo; Varela, H.; Valladares, Francisco; Álvarez-Argüelles, H.; Díaz-Flores, Lucio
Adult stem cells (ASC) -able to self renew and to intervene in maintaining the structural and functional integrity of their original tissue- can express greater plasticity than traditionally attributed to them, adopting functional phenotypes and expression profiles of cells from other tissues. Therefore, they could be useful to regenerative medicine and tissue engineering. Transit-amplifying cells (TAC) are committed progenitors among the ASC and their terminally differentiated daughter cells. The ASC reside in a specialized physical location named niche, which constitutes a three-dimensional microenviroment where ASC and TAC are protected and controlled in their selfrenewing capacity and differentiation. The niche can be located near or far from the recruitment point, requiring a short or long-distance cellular migration, respectively. This paper briefly reviews the current status of research about ASC plasticity, transdifferentiation, fusion and functional adaptation mechanisms. Subsequently, ASC and TAC occurrence, characteristics and location have been considered in the skin, cornea, respiratory tract, teeth, gastrointestinal tract, liver, pancreas, salivary glands, kidney, breast, prostate, endometrium, mesenchyma, bone marrow, skeletal and cardiac muscle, nervous system and pituitary gland. Moreover, the role of cancer ASC has also been revised.
Open Access
BMI-1: a protein expressed in stem cells, specialized cells and tumors of the gastrointestinal tract
(Murcia : F. Hernández, 2006) Reinisch, C.; Kandutsch, S.; Uthman, A.; Pammer, J.
Recently, BMI-1 was identified as a protein downregulating p16ink4a and mandatory for the continued existence of several stem cell compartments like hematopoietic and neural stem cells. In this study we investigated BMI-1 expression as a potential stem cell marker of the gastrointestinal tract. We found weak expression in the isthmus region of the stomach, and moderate expression in crypts of the intestines, whereas intestinal surface epithelial cells were weakly positive or negative for BMI-1. In addition, a variety of highly differentiated cells such as parietal cells, neuroendocrine cells of the pylorus, Paneth cells and a subset of goblet cells were moderately to strongly positive for BMI-1. Furthermore, we detected strong expression in gastrointestinal neoplasias. This expression pattern indicates a correlation of BMI-1 expression with gastrointestinal stem cells as well as numerous specialized cell types and points to a role of this protein in cellular differentiation in addition to that of stem cell maintenance. Besides, our results imply a role for BMI-1 in the tumorigenesis of gastrointestinal cancer.
Open Access
Cells from the inner mass of blastocyst as a source of neural derivates for differentiation studies
(Murcia : F. Hernández, 2004) Álvarez, A.; Gómez-Urquijo, S.; Ramos, A.; Hilario, E.
Our results show that cells derived from the inner cell mass (ICM) show a clear tendency to differentiate into the neural lineage, showing both cells and structures in different degrees of differentiation. Among the experimental paradigms used to learn about neural differentiation, there have been several lines of investigation on stem cells, including embryonic stem (ES) cells isolated from the inner cell mass of embryo and also stem cells derived from embryonic carcinoma (EC). In this work, we have used a cellular line obtained from the inner cell mass of a blastocyst. The cells were cultured and after inoculated subcutaneously in syngenic mice. The neural differentiation was predominant, and could be observed both by morphological and immunohistochemical methods. It was represented by neural-tubes, neurons and glial cells, as expressed by the presence of Microtubule-associated protein-2 (MAP-2) and glial fibrilary acidic protein. Moreover, tyrosine hydroxilase positive labelling was found in neuron-like cells, which suggest the chatecolaminergic differentiation. These results show that isolation of cells from the inner mass of blastocyst represents an easy, reproducible and cheap source of neural derivates suitable for both in vivo and in vitro differentiation studies.
Open Access
Characterization of rat testicular teratoma and its derived cell lines, with particular reference to possible mesenchymal differentiations
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Yamate, Jyoji; Gamou, Katsuhiro; Izawa-Ogata, Keiko; Kotera, Takashi; Izawa, Takeshi; Takenaka, Shigeo; Sawamoto, Osamu; Kuwamura, Mitsuru
The original tumor, 4 cm in diameter, was found in the left testis of a 2-month old SD rat. The tumor consisted of well-differentiated, mature tissues such as bone, cartilage, adipose tissue, smooth and skeletal muscles, skin, hair, glands (salivary, sebaceous, apocrine and pancreatic exocrine glands) and trachea, as well as nerve tissues. The tumor was diagnosed as a mature type of teratoma, a rare in rat testis. Cloned cell lines (named TSD-B4S and TSD-F9R) were established from the tumor; cellular properties of these cell lines were similar to each other; basically, their cultured cells exhibited vimentin-positive mesenchymal nature with occasional cells reacting to α-smooth muscle actin, glial fibrillary acidic protein and CD163 (a macrophage marker). The cell lines showed tumorigenicity when inoculated into nude mice, being composed of immature mesenchymal cells arranged mainly in a sheet. In TSDB4S cells treated with differentiation factors, we demonstrated mesenchymal differentiations towards adipogenic, osteogenic and myofibrogenic cells. The cell line (TSD-B4S) would become a useful tool for studies on stem cell differentiation, because the teratoma arises from primordial germ cells like embryonic stem cells.
Open Access
Clinical significance of ALDH1A1 and Ki67 expression in women with breast carcinoma
(Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Zong Yuxuan; Ma Shuang; Yin Jiaxin; Qiao Na; Zhang Dongmei; Niu Zhaoyang; Zhao Ye; Zhou Fei; Biología Celular e Histología
Background. Breast cancer is the most prominent cancer among women worldwide, with a two-fold incidence in China compared to the worldwide incidence. ALDH1A1, catalyzing the oxidation of intracellular aldehydes and converting retinol into retinoic acid, serves as a biomarker of early stem cell differentiation. Ki67 levels are prognostic or residual risk biomarkers after primary therapy and can predict the effects of systemic therapies or monitor patients for sustained response or resistance to the administered therapies. This study aimed to investigate the correlation between ALDH1A1 and Ki67 expression and clinicopathological parameters among women with breast cancer. Methods. Breast cancer tissue specimens were obtained from the Department of Pathology at the First Hospital of Qiqihar. Indirect fluorescent immunostaining was used to assess the expression of ALDH1A1 and Ki67 in breast cancer and healthy tissues. Associations between ALDH1A1 and Ki67 expression and clinicopathological parameters of breast cancer were evaluated using the chi-square test. A p-value less than 0.05 was considered statistically significant. The correlation between ALDH1A1 and Ki67 expression was assessed using Spearman’s rank correlation analysis. Results. ALDH1A1 and Ki67 were upregulated in breast cancer tissue compared with normal breast tissue (p<0.05). Furthermore, ALDH1A1 expression was further upregulated with an advancement in breast cancer grade, i.e., ALDH1A1 expression levels were higher in patients with stage III/IV breast cancer than in those with stage I/II breast cancer. Furthermore, ALDH1A1 and Ki67 were upregulated in the presence of lymphatic metastasis. Conclusion. ALDH1A1 may be considered a pathognomonic marker for breast cancer. ALDH1A1 and Ki67 expression are significantly positively correlated in women with breast cancer.
Open Access
Defining adipose tissue-derived stem cells in tissue and in culture
(Murcia: F. Hernández, 2010) Lin, Ching-Shwun; Xin, Zhong-Cheng; Deng, Chun-Hua; Ning, Hongxiu; Lin, Guiting; Lue, Tom F.
Adipose tissue-derived stem cells (ADSC) are routinely isolated from the stromal vascular fraction (SVF) of homogenized adipose tissue. Similar to other types of mesenchymal stem cells (MSC), ADSC remain difficult to define due to the lack of definitive cellular markers. Still, many types of MSC, including ADSC, have been shown to reside in a perivascular location, and increasing evidence shows that both MSC and ADSC may in fact be vascular stem cells (VSC). Locally, these cells differentiate into smooth muscle and endothelial cells that are assembled into newly formed blood vessels during angiogenesis and neovasculogenesis. Additionally, MSC or ADSC can also differentiate into tissue cells such as adipocytes in the adipose tissue. Systematically, MSC or ADSC are recruited to injury sites where they participate in the repair/regeneration of the injured tissue. Due to the vasculature’s dynamic capacity for growth and multipotential nature for diversification, VSC in tissue are individually at various stages and on different paths of differentiation. Therefore, when isolated and put in culture, these cells are expected to be heterogeneous in marker expression, renewal capacity, and differentiation potential. Although this heterogeneity of VSC does impose difficulties and cause confusions in basic science studies, its impact on the development of VSC as a therapeutic cell source has not been as apparent, as many preclinical and clinical trials have reported favorable outcomes. With this understanding, ADSC are generally defined as CD34+CD31- although loss of CD34 expression in culture is well documented. In adipose tissue, CD34 is localized to the intima and adventitia of blood vessels but not the media where cells expressing alpha-smooth muscle actin (SMA) exist. By excluding the intima, which contains the CD34+CD31+ endothelial cells, and the media, which contains the CD34-CD31- smooth muscle cells, it leaves the adventitia as the only possible location for the CD34+ ADSC. In the capillary, CD34 and CD140b (a pericyte marker) are mutually exclusively expressed, thus suggesting that pericytes are not the CD34+ ADSC. Many other cellular markers for vascular cells, stem cells, and stem cell niche have also been investigated as possible ADSC markers. Particularly the best-known MSC marker STRO-1 has been found either expressed or not expressed in cultured ADSC. In the adipose tissue, STRO-1 appears to be expressed exclusively in the endothelium of certain but not all blood vessels, and thus not associated with the CD34+ ADSC. In conclusion, we believe that ADSC exist as CD34+CD31-CD104b-SMA- cells in the capillary and in the adventitia of larger vessels. In the capillary these cells coexist with pericytes and endothelial cells, both of which are possibly progenies of ADSC (or more precisely VSC). In the larger vessels, these ADSC or VSC exist as specialized fibroblasts (having stem cell properties) in the adventitia.
Open Access
Immunohistochemical evaluation of intermediate filament nestin in dog hair follicles
(Murcia : F. Hernández, 2008) Mercati, F.; Pascucci, L.; Gargiulo, A.M.; Dall’Aglio, C.; Ceccarelli, P.
Hair follicles (HFs) are self-renewing structures that reconstitute themselves through the hair cycle. They maintain reservoirs of stem cells (SC) that are thought to reside in the bulge area, a region localized in the lowermost permanent portion of HFs. In mice and humans, HF bulge cells express nestin and present stem features as pluripotency. Nestin is a class VI intermediate filament protein; it was first described as a specific marker of CNS stem cells, but recent studies suggest that it may represent a more general stem cell marker (Wiese et al., 2004; Hoffman, 2006). Bulge cell characteristics have mainly been studied in mice and humans, but recently, a bulge-like region was identified also in dog HFs (Pascucci et al., 2006). In this work we investigate the presence and localization of nestin in dog HFs with the aim of evaluating its expression and to correlate it with the location of the bulge-like region. Immunostaining of skin samples collected from healthy dogs was performed by using a rabbit anti-nestin polyclonal antibody. The presence of a population of immunoreactive cells was revealed in the hair follicle middle region, at the arrector pili muscle insertion level. An immunohistochemical signal was detected only in primary hair follicles throughout the hair cycle. These observations led us to conclude that nestin positive cells are located in the bulge-like region of dog HFs and strengthen our hypothesis regarding the correlation between this region and the dog HF stem compartment.
Open Access
Karyotypic analysis of adult pluripotent stem cells
(Murcia : F. Hernández, 2005) Henson, N.L.; Heaton, M.L.; Holland, B.H.; Hawkins, K.C.; Rawlings, B.A.; Eanes, E.A.; Bozof, R.G.; Powell, S.W.; Grau, R.E.; Fortney, J.A.; Peebles, B.G.; Kumar, D.; Yoon, J.I.; Godby, K.N.; Collins, J.A.; Sood, R.; Hixson, D.; Bowyer III, F.P.; Black Jr., A.C.; Young, H.E.
Three categories of precursor cells have been identified in postnatal mammals: tissue-committed progenitor cells, germ layer lineage-committed stem cells and lineage-uncommitted pluripotent stem cells. Progenitor cells are the immediate precursors of differentiated tissues. Germ layer lineage stem cells can be induced to form multiple cell types belonging to their respective ectodermal, mesodermal, and endodermal embryological lineages. Pluripotent stem cells will form somatic cell types from all three primary germ layer lineages. Progenitor cells demonstrate a finite life span before replicative senescence and cell death occur. Both germ layer lineage stem cells and pluripotent stem cells are telomerase positive and display extensive capabilities for self-renewal. Stem cells which undergo such extensive replication have the potential for undergoing mutations that may subsequently alter cellular functions. Gross mutations in the genome may be visualized as chromosomal aneuploidy and/or chromosomes that appear aberrant. This study was designed to determine whether any gross genomic mutations occurred within the adult pluripotent stem cells. Karyotypic analysis was performed using pluripotent stem cells purified from adult male rats using established procedures. Giemsa Banding was used in conjuction with light microscopy to visualize metaphase chromosome spreads. To date over 800 metaphase spreads have been analyzed. We found that the metaphase spreads averaged 42 chromosomes and concluded that these pluripotent stem cells isolated from adult rats have a normal karyotype.
Open Access
Pathophysiology of stem cells in restenosis
(Murcia : F. Hernández, 2007) Forte, A.; Cipollaro, M.; Cascino, A.; Galderisi, U.
Recent evidence has shown that vascular function depends not only on cells within the vessels, but is also significantly modulated by circulating cells derived from the bone marrow. A number of studies indicate that an early reendothelialization by circulating endothelial precursors after vascular injury prevents excessive cell proliferation and restenosis. Conversely, other studies concluded that the homing of other cell fractions, consisting mainly of smooth muscle precursors, cause pathological remodelling. Different cell types have been identified and characterized so far as circulating precursors able to participate in vascular repair by homing and differentiating towards endothelial cells or smooth muscle cells. Among these, endothelial precursor cells, smooth muscle progenitor cells, mesenchymal stem cells and others have been described. The origins, the hierarchy, the role and the markers of these different cell populations are still controversial. Nevertheless, different strategies have been developed so far in animal models to induce the mobilization and the recruitment of stem cells to the injury site, based on physical training, hormone injection and application of stem cell-capturing coated stents. It should also be mentioned that the limited data currently available derived from clinical trials provide contrasting results about the effective role of vascular cell precursors in restenosis prevention, thus indicating that conclusions derived from studies in animal models cannot always be directly applied to humans and that caution should be used in the manipulation of circulating progenitor cells for therapeutic strategies.
Open Access
Proliferation and migration kinetics of stem cells in the rat fundic gland
(Murcia : F. Hernández, 1997) Yang, D.H.; Tsuyama, S.; Ge, Y. B.; Wakamatsu, D.; Ohmori, J.; Murata, F.
The proliferation and migration of stem cells in the developing and adult rat fundic gland have been studied using BrdU immunohistochemistry and BrdUGSA 11 (Griffonia-simplicifolia agglutinin-11) double staining. In the developing rat fundic gland, stem cells were first scattered throughout al1 levels of the epithelia and then concentrated in the depth of the pits. With the elongation and maturation of the fundic glands, stem ceils left the gland base and moved upward. By 4 weeks after birth, the development of the fundic gland was completed and stem cells were confined to a narrow proliferative zone in the isthmus, reaching the adult distribution pattern. In the adult rat fundic gland, stem cells in the isthmus differentiated and migrated upward and downward, replacing the surface mucous cells and glandular cells respectively. For upward migration, it took about one week for stem cells to migrate from the isthmus to the surface. For downward migration, it took about two weeks for stem cells to migrate from the isthmus to the neck, and it took 30-36 weeks to reach the gland unit's blind end. FinaJly stem cells were lost at the deepest leve1 of the glands. The results obtained by simple topographical distribution in the present experiment agreed well with those obtained by quantitative analysis, suggesting the usefulness of BrdU immunohistochemistry for cell kinetic studies.
Open Access
Stem cells and germ cells, microRNA and gene expression signatures
(Murcia : F. Hernández, 2010) Dyce, Paul William; Toms, Derek; Li, Julang
The study of primordial germ cell development in vivo is hampered by their low numbers and inaccessibility. Recent research has shown the ability of embryonic and adult stem cells to differentiate into primordial germ cells and more mature gametes and this generation of germ cells in vitro may be an attractive model for their study. One of the biggest challenges facing in vitro differentiation of stem cells into primordial germ cells is the lack of markers to clearly distinguish the two. As both cell types originate early in embryonic development they share many pluripotent markers such as OCT4, VASA, FRAGILIS, and NANOG. Genome wide microarray profiling has been used to identify transcriptome patterns unique to primordial germ cells. A more thorough analysis of the temporal and quantitative expression of a panel of genes may be more robust in distinguishing these two cell populations. MicroRNAs, short RNA molecules that have been shown to regulate translation through interactions with mRNA transcripts, have also recently come under investigation for the role they may play in pluripotency. Attempts to elucidate key microRNAs responsible for both stem cell and primordial germ cell characteristics have recently been undertaken. Unique microRNAs, either individually or as global profiles, may also help to distinguish differentiated primordial germ cells from stem cells in vitro. This review will examine gene expression and microRNA signatures in stem cells and germ cells as ways to distinguish these closely related cell types.
Open Access
Stem cells in human breast cancer
(Murcia : F. Hernández, 2010) Roberto Oliveira, Lucinei; Jeffrey, Stefanie S.; Ribeiro Silva, Alfredo
Increasing data support cancer as a stem cell-based disease. Cancer stem cells (CSCs) have beenfound in different human cancers, and recent evidenceindicates that breast cancer originates from and ismaintained by its own CSCs, as well as the normalmammary gland. Mammary stem cells and breast CSCshave been identified and purified in in vitroculturesystems, transplantation assays and/or by cell surfaceantigen identification. Cell surface markers enable thefunctional isolation of stem cells that can initiate andpropagate tumorigenesis in mammary gland. Theseobservations have dramatic biological and clinicalsignificance due to increasing evidence suggesting thatthe recurrence of human cancer and treatment failuremay reflect the intrinsic quiescence and drug resistanceof CSCs. Thus, the CSC hypothesis providesfundamental implications for understanding breastcarcinogenesis and for developing new strategies forbreast cancer prevention and therapy for advanceddisease. Further strategies to isolate breast CSCs, to findadditional trustworthy surface markers, and to comparegene expression pathways profiles with their normalstem cells counterparts are necessary to more accuratelydefine putative breast cell-lineage markers for thedifferent cell types present in the mature mammarygland and to identify potential therapeutical targets inbreast cancer. This review discusses the currentknowledge about stem cells and CSCs, focusing onmammary stem cells and breast CSCs, and theirconsequences for breast tumorigenesis and implicationsfor breast cancer susceptibility, prognosis, and treatment.
Open Access
Stem cells: Are they the answer to the puzzling etiology of endometriosis?
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Oliveira, Flávia R.; Dela Cruz, Cynthia; Del Puerto, Helen L.; Vilamil, Quésia T.M.F.; Reis, Fernando M.; Camargos, Aroldo F.
Endometriosis is a chronic bening disease characterizaed by the presence of abnormally located tissue resembling the endometrium with glands and stroma. This disease has a high degree of morbidity due to chronic pelvic pain and infertility. The disease is likely to be polygenic and multifactorial, but the exact pathogenic mechanisms are still not entirely clear. Recently, adult stem cells have been identified in several tissues, including the endometrium. These cells are probably involved in the regenerative ability of the endometrial cycle, and also in the pathogenesis of proliferative gynaecological diseases, such as endometriosis. The identification of stem cells in animal and human tissues is very complex and the putative stem cells are supposed to be found through several assays such as clonogenicity, label-retaining cells, “side- population” cells, undifferentiation markers, and cellular differentiation. Bone marrow-derived stem cells transplanted into humans and animals have also been identified in eutopic endometrium and endometriotic implants. This review evaluates the available evidence regarding stem/progenitor cells in the human endometrium and explores the possible involvement of these cells in the etiology of endometriosis.
Open Access
The amniotic membrane as a source of stem cells
(Murcia : F. Hernández, 2010) Insausti, Carmen L.; Blanquer Blanquer, Miguel; Bleda, Patricia; Iniesta, Paqui; Majado Martínez, Mª Juliana; Castellanos Escrig, Gregorio; Moraleda Jiménez, José María
Cellular therapy has emerged as a new potential tool for curing a wide range of degenerative diseases and tissue necrosis. Embryonic stem cells possess potential for differentiation into a wide range of cell lineages, but the ethical issues associated with establishment of this human cell line have to be resolved prior to any use. The bone marrow (BM) is the usual source of adult stem cells for hematopoietic stem cell transplants and cellular therapy, but the BM harvest is a surgical procedure that requires general anesthesia or sedation, and there seems to be a reduction of the proliferative potential and differentiation capacity of the marrow mesenchymal stem cells in older donors. For these reasons there is an increasing interest in other sources of stem cells from adult and fetal tissues. The amniotic membrane (AM) or amnion is a tissue of particular interest because its cells possess characteristics of stem cells with multipotent differentiation ability, and because of low immunogenicity and easy procurement from the placenta, which is a discarded tissue after parturition, thus avoiding the current controversies associated with the use of human embryonic stem cells. Therefore, amniotic membrane has been proposed as a good candidate to be used in cellular therapy and regenerative medicine.
Open Access
The application of stem cells in the treatment of ischemic diseases
(Murcia : F. Hernández, 2006) Chen, C.P.; Lee, Y.J.; Chiu, S.T.; Shyu, W.C.; Lee, M.Y.; Huang, S.P.; Li, H.
Ischemia causes oxygen deprivation, cell injury and related organ dysfunction. Although ischemic injury may be local, it involves many biochemical changes in different cell types. The ability of stem cells to differentiate into different cell lineages provides the possibility of their use in treating a variety of diseases requiring tissue repair or reconstitution, such as stroke, ischemic retinopathy, myocardial infarction, ischemic disorders of the liver, ischemic renal failure, and ischemic limb dysfunction. Several cell types including embryonic stem cells, various progenitor and stem cells of hematopoietic or mesenchymal origin have been used in attempts to reconstitute injured tissue. Xenologous or autologous stem cells may be administered either through the peripheral vascular system or directly by regional injection. The stem cells are then guided to the infarct site by homing signals. Either by cell differentiation or paracrine effects, stem cells or progenitor cells participate in the reconstruction of a favorable microenvironment resulting in neovascularization and tissue regeneration that eventually improve the physiological function of organs with ischemic damage.
Open Access
The CCN proteins: important signaling mediators in stem cell differentiation and tumorigenesis
(Murcia: F. Hernández, 2010) Zuo, Guo-Wei; Kohls, Christopher D.; He, Bai-Cheng; Chen, Liang; Zhang, Wenli; Shi, Qiong; Zhang, Bing-Qiang; Kang, Quan; Luo, Jinyong; Luo, Xiaoji; Wagner, Eric R.; Kim, Stephanie H.; Restegar, Farbod; Haydon, Rex C.; Deng, Zhong-Liang; Luu, Hue H.; He, Tong-Chuan; Luo, Qing
The CCN proteins contain six members, namely CCN1 to CCN6, which are small secreted cysteine-rich proteins. The CCN proteins are modular proteins, containing up to four functional domains. Many of the CCN members are induced by growth factors, cytokines, or cellular stress. The CCNs show a wide and highly variable expression pattern in adult and in embryonic tissues. The CCN proteins can integrate and modulate the signals of integrins, BMPs, VEGF, Wnts, and Notch. The involvement of integrins in mediating CCN signaling may provide diverse contextdependent responses in distinct cell types. CCN1 and CCN2 play an important role in development, angiogenesis and cell adhesion, whereas CCN3 is critical to skeletal and cardiac development. CCN4, CCN5 and CCN6 usually inhibit cell growth. Mutations of Ccn6 are associated with the progressive pseudorheumatoid dysplasia and spondyloepiphyseal dysplasia tarda. In stem cell differentiation, CCN1, CCN2, and CCN3 play a principal role in osteogenesis, chondrogenesis, and angiogenesis. Elevated expression of CCN1 is associated with more aggressive phenotypes of human cancer, while the roles of CCN2 and CCN3 in tumorigenesis are tumor type-dependent. CCN4, CCN5 and CCN6 function as tumor suppressors. Although CCN proteins may play important roles in fine-tuning other major signaling pathways, the precise function and mechanism of action of these proteins remain undefined. Understanding of the biological functions of the CCN proteins would not only provide insight into their roles in numerous cellular processes but also offer opportunities for developing therapeutics by targeting CCN functions.
Open Access
The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated transfer of genetic information
(Murcia : F. Hernández, 2010) Deregibus, Maria Chiara; Tetta, Ciro; Camussi, Giovanni
It has been commonly supposed that adultstem cells co-localize with supporting cells withinspecific regions or specialized microenvironment in eachtissue/organ, called stem cell niche. This concept wasbased on the assumption that stem cells are intrinsicallyhierarchical in nature. However, recent data indicate thatstem cells may represent a continuum with reversiblealterations in phenotype taking place during the transitthrough cell cycle. Based on this dynamic interpretationit has been suggested that the so-called niche isrepresented by a single or only few cell types continuallyadjusting their phenotype and function to individualcircumstances. A critical component in the regulation ofthe continuum of stem cell phenotypes is themicroenvironment. In this context, microvesicles (MVs)account for the transfer of genetic information betweencells. Originally considered inert cellular debris, MVsare increasingly recognized to be important mediators ofcell-to-cell communication. MVs may transfer receptors,proteins, mRNA and microRNA to target cells viaspecific receptor-mediated interaction. In stem cellbiology the exchange of genetic information may bebidirectional from stromal to stem cells. In the context oftissue injury the MV-mediated transfer of geneticinformation may reprogram the phenotype of stem cellsto acquire features of the injured tissue cells. In addition,MVs derived from stem cells may induce de-differentiation of cells which have survived injury with acell cycle re-entry that may allow tissue regeneration. Inthe present review we discuss the possibility of acontinuous genetic modulation of stem cells by a MV-mediated transfer of information between cells.
Open Access
The therapeutic potential of human olfactory-derived stem cells
(Murcia : F. Hernández, 2006) Marshall, C.T.; Lu, C.; Winstead, W.; Zhang, X.; Xiao, M.; Harding, G.; Klueber, K.M.; Roisen, F.J.
Stem cells from fetal and adult central nervous system have been isolated and characterized, providing populations for potential replacement therapy for traumatic injury repair and neurodegenerative diseases. The regenerative capacity of the olfactory system has attracted scientific interest. Studies focusing on animal and human olfactory bulb ensheathing cells (OECs) have heightened the expectations that OECs can enhance axonal regeneration and repair demyelinating diseases. Harvest of OECs from the olfactory bulb requires highly invasive surgery, which is a major obstacle. In contrast, olfactory epithelium (OE) has a unique regenerative capacity and is readily accessible from its location in the nasal cavity, allowing for harvest without lasting damage to the donor. Adult OE contains progenitors responsible for the normal life-long continuous replacement of neurons and supporting cells. Culture techniques have been established for human OE that generate populations of mitotically active neural progenitors that form neurospheres (Roisen et al., 2001; Winstead et al., 2005). The potential application of this technology includes autologous transplantation where minimal donor material can be isolated, expanded ex vivo, and lineage restricted to a desired phenotype prior to/or after re-implantation. Furthermore, these strategies circumvent the ethical issues that arise with embryonic or fetal tissues. The long term goal is to develop procedures through which a victim of a spinal cord injury or neurodegenerative condition would serve as a source of progenitors for his/her own regenerative grafts, avoiding the need for immunosuppression and ethical controversy. In addition, these cells can provide populations for pharmacological and/or diagnostic evaluation.
Open Access
Tumour morphology - interplay between chromosome aberrations and founder cell differentiation
(Murcia : F. Hernández, 2002) Gisselsson, D.
Studies of haematological neoplasms have shown that alterations in structure and/or expression of transcription factor genes may play a crucial role for transforming stem cells or progenitor cells into malignant cells. These mutations typically arise through balanced translocations and appear to induce a block in cellular differentiation. The impact of the transforming mutation is highly dependent on the lineage of the founder cell and each specific translocation is limited to one or a few morphological subtypes. Originating from immature cells, these neoplasms have a high selfreplicative capacity and are already before transformation protected from senescence by constitutive telomerase expression. Most solid tumours, on the other hand, probably originate from cells at higher levels of differentiation and require multiple mutations in oncogenes and tumour suppressor genes for neoplastic transformation. Absence of telomerase activity in the tumour-founding cell line predisposes to abnormal shortening of telomeric repeats in these cells during early clonal expansion. In turn, this triggers chromosomal breakage-fusion-bridge events through which the tumour genome is constantly reorganised, resulting in a complex and heterogeneous pattern of chromosome aberrations in the tumour cell population; the abnormal mitotic processes also give rise to cellular pleomorphism and nuclear atypia. Tumour morphology thus appears to be determined not only by the lineage of the transformed cell but also by its propensity for chromosomal instability.

Browsing by Subject "Stem cell"

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