scholarly journals Regulation of Prostatic Stem Cells by Stromal Niche in Health and Disease

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4303-4306 ◽  
Author(s):  
Gail P. Risbridger ◽  
Renea A. Taylor
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Tumor Stroma ◽  
Stem Cell Differentiation ◽  
Stem Cell Regulation ◽  
Isolation And Characterization ◽  
Tissue Recombination ◽  
Cell Niche

The isolation and characterization of prostatic stem cells has received significant attention in the last few years based on the belief that aberrant regulation of adult stem cells leads to prostate disease including cancer. The nature of the perturbations in stem cell regulation remains largely unknown. Although adult stem cells are can be governed by autonomous regulatory mechanisms, the stromal niche environment also provides essential cues to direct directing differentiation decisions and can lead to aberrant proliferation and/or differentiation. Elegant tissue recombination experiments, pioneered by Gerald Cunha and colleagues, provided evidence that quiescent epithelial tissues containing adult stem cells were capable of altered differentiation in response to inductive and instructive mesenchyme. In more recent times, it has been demonstrated that embryonic mesenchyme is sufficiently powerful to direct the differentiation of embryonic stem cells into mature prostate or bladder. In addition, prostatic tumor stroma provides another unique niche or microenvironment for stem cell differentiation that is distinct to normal stroma. This review highlights the importance of the appropriate selection of the stromal cell niche for tissue regeneration and implies plasticity of adult stem cells that is dictated by the tissue microenvironment.

scholarly journals A Case of Identity: HOX Genes in Normal and Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 512 ◽  
Author(s):  
Smith ◽  
Zyoud ◽  
Allegrucci
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Cancer Stem Cells ◽  
Adult Stem Cells ◽  
Hox Genes ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Hox Gene

Stem cells are undifferentiated cells that have the unique ability to self-renew and differentiate into many different cell types. Their function is controlled by core gene networks whose misregulation can result in aberrant stem cell function and defects of regeneration or neoplasia. HOX genes are master regulators of cell identity and cell fate during embryonic development. They play a crucial role in embryonic stem cell differentiation into specific lineages and their expression is maintained in adult stem cells along differentiation hierarchies. Aberrant HOX gene expression is found in several cancers where they can function as either oncogenes by sustaining cell proliferation or tumor-suppressor genes by controlling cell differentiation. Emerging evidence shows that abnormal expression of HOX genes is involved in the transformation of adult stem cells into cancer stem cells. Cancer stem cells have been identified in most malignancies and proved to be responsible for cancer initiation, recurrence, and metastasis. In this review, we consider the role of HOX genes in normal and cancer stem cells and discuss how the modulation of HOX gene function could lead to the development of novel therapeutic strategies that target cancer stem cells to halt tumor initiation, progression, and resistance to treatment.

Oct4 and Its Pseudogenes Confuse Stem Cell Research.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3700-3700
Author(s):  
Stefanie Liedtke ◽  
Jürgen Enczmann ◽  
Simon Waclawczyk ◽  
Peter Wernet ◽  
Gesine Kögler
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Differentiated Cells ◽  
Alternatively Spliced

Abstract Octamer-binding transcription factor 4 (Oct4) encodes a nuclear protein that belongs to a family of transcription factors containing the POU DNA binding domain. It is specifically expressed in embryonic stem cells but can also be detected in adult stem cells such as bone marrow-derived mesenchymal stem cells. The expression of Oct4 is down-regulated coincident with stem cell differentiation and loss of expression leading to differentiation. It plays a critical role for maintaining pluripotency and self-renewal of embryonic stem cells. However, the usefulness of Oct4 as a pluripotency marker was challenged recently. More and more data seem to support that Oct4 is expressed on a variety of differentiated cells, including peripheral blood mononuclear cells. Taking into account that RT-PCR can potentially generate experimental artifacts due to pseudogene transcripts, the existence of Oct4 pseudogenes should be investigated further here. Suo et al. were able to detect transcription of some Oct4 pseudogenes in cancer cell lines as well as cancer tissues. These results show that some of the known Oct4 pseudogenes are transcribed in vivo and therefore could lead to RT-PCR artifacts. However this known problem was not seriously taken into consideration in recent publications on adult stem cells and tissue analysis referring to Oct4. We started with an initial alignment of Oct4 compared to its alternative splice variants as well as its pseudogenes. This alignment served as a prerequisite for an exact primer design. First the sequence and organization of the functional human Oct4 gene were clarified to allow comparison to the pseudogenes and alternatively spliced transcripts. The NCBI human EST database was searched and the UniGene cluster for Oct4 (NM_002701) examined. This yielded 13 mRNA sequences and 129 EST sequences. An additional BLASTn search of the human genome using single exons of Oct4 revealed several other highly similar sequences. All these hits encoded complete or partial Oct4 sequences and could therefore represent either functional members of an Oct4 gene family or pseudogenes. The fact that so many homologous sequences resemble the original Oct4 transcript makes an RT-PCR analysis difficult, because a lot of artifacts can arise during amplification. Therefore primers were designed which are able to exclude amplification of all unwanted transcripts. To conclude, based on the fact that the expression of Oct4 has been reported in adult stem cells as well as in a variety of differentiated cells the possibility cannot be excluded that the detected Oct4 signal came from alternatively spliced or Oct4 pseudogene transcripts. As shown here, an exact design of Oct4-specific primers is an inevitable prerequisite for appropriate RT-PCR analysis. In addition, a careful comparison of quantitative differences to human embryonic stem cells should be present too, before cells are described as embryonic like cells. We hope that our findings will help other stem cell researchers to find their appropriate tools especially for RT-PCR analysis and give an example how later problematic artifacts can be ruled out from the beginning by a detailed alignment as a prerequisite for designing appropriate primers.

scholarly journals Challenges of stem cell application in research and clinical practice – an update

2021 ◽  
Vol 9 (4) ◽  
pp. 160-164
Author(s):  
Maurycy Jankowski ◽  
Marie Machatkova ◽  
Pavel Ventruba ◽  
Elena Kistanova ◽  
Alexander Makarevich ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Practice ◽  
Large Scale ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Human Organism ◽  
Adverse Side Effect

Abstract There are multiple possible applications of stem cells in medicine, from cell-based therapies for degenerative and dystrophic conditions, through novel approaches in cancer treatment, to in vitro organ printing. However, there are still several challenges that need to be overcame before stem cells therapies can be successfully introduced worldwide on a large scale. These include sourcing of stem cells, preventing their aberrant progression and ethical concerns regarding their use in animals and humans. Among the multiple stem cell types present in the human organism from the period of embryonic development to adulthood, this review focuses on the three types that gain the most attention in relation to modern research: embryonic stem cells, induced pluripotent stem cells and adult stem cells. There are a number of obstacles that need to be removed before these cells can be widely applied in clinical practice, including the choice of the perfect source of stem cells, full elucidation of the mechanisms of stem cell differentiation and plasticity, and minimization of adverse side effect potential. Nonetheless, the focus of the scientific community on the topic of stem cells remains unhindered, bringing hope that all of the possible concerns will be addressed in the future.

Oct4 expression revisited: potential pitfalls for data misinterpretation in stem cell research

2008 ◽  
Vol 389 (7) ◽  
Author(s):  
Stefanie Liedtke ◽  
Milaid Stephan ◽  
Gesine Kögler
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Mononuclear Cells ◽  
Embryonic Stem ◽  
Human Tumor ◽  
Stem Cell Differentiation ◽  
Self Renewal ◽  
Oct4 Expression

Abstract The octamer-binding transcription factor 4 gene encodes a nuclear protein (Oct4, also known as Pou5F1 and Oct3/4) that belongs to a family of transcription factors containing the POU DNA-binding domain. Expression can be detected in embryonic stem cells as well as in adult stem cells, such as bone marrow-derived mesenchymal stem cells. Expression of Oct4 is downregulated coincident with stem cell differentiation and loss of expression leading to differentiation. A role for maintaining pluripotency and self-renewal of embryonic stem cells is ascribed to Oct4 as a pluripotency marker. Results describing Oct4 expression in differentiated cells, including peripheral blood mononuclear cells (PBMCs), neonatal and adult stem cells, as well as cancer cells, must be interpreted with caution. In several publications, Oct4 has been ascribed a function in maintaining self-renewal of adult stem cells. In contrast, other publications reported Oct4 expression in human tumor cells. Here, we summarize the recent findings on Oct4 expression and present possibilities and reasons why several false positive results on Oct4 expression still occur in the recent literature. Also, simple solutions are provided to avoid these positive signals.

scholarly journals Induction of Cancerous Stem Cells during Embryonic Stem Cell Differentiation

2012 ◽  
Vol 287 (44) ◽  
pp. 36777-36791 ◽  
Author(s):  
Hiroaki Fujimori ◽  
Mima Shikanai ◽  
Hirobumi Teraoka ◽  
Mitsuko Masutani ◽  
Ken-ichi Yoshioka
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation

scholarly journals Maintenance of Adult Stem Cells: Role of the Stem Cell Niche

2011 ◽  
pp. 35-55 ◽  
Author(s):  
Yoshiko Matsumoto ◽  
Hiroko Iwasaki ◽  
Toshio Suda
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Adult Stem Cells ◽  
Cell Niche

Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Us ◽  
Health Database ◽  
Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

291 ISOLATION AND CHARACTERIZATION OF MESENCHYMAL STEM CELLS DERIVED FROM HUMAN AMNIOTIC FLUID

2011 ◽  
Vol 23 (1) ◽  
pp. 243 ◽  
Author(s):  
S.-A. Choi ◽  
J.-H. Lee ◽  
K.-J. Kim ◽  
E.-Y. Kim ◽  
K.-S. Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Amniotic Fluid ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Stem Cell Marker ◽  
Second Trimester ◽  
Cell Marker ◽  
Human Amniotic Fluid ◽  
Amniotic Fluid Stem Cells

Adult stem cells have the capacity to differentiate into several different cell types, although their differentiation potential is limited compared with that of embryonic stem cells. Thus, adult stem cells are regarded as an exciting source for new cell therapies. Recent observations also indicate that stem cells derived from second-trimester amniocentesis are pluripotent – capable of differentiating into multiple lineages, including representatives of all 3 embryonic germ layers. In addition, amniotic fluid stem cells can be used in the generation of disease- or patient-specific stem cells, and amniotic fluid stem cells could be an ideal source for autologous cell replacement therapy in the later life of the fetus. The aim of the present study was to investigate isolation and characterisation of human amniotic fluid-derived mesenchymal stem cells (hAFS). We successfully isolated and characterised hAFS. Amniotic fluid samples were collected in the second trimester (median gestational age: 16 weeks, range: 15–17 weeks) for prenatal diagnosis. Specimens (2 mL) were centrifuged and incubated in low-glucose DMEM supplemented with 10% FBS, 25 ng of basic fibroblast growth factor, and 10 ng of epidermal growth factor at 37°C with 5% CO2. Human amniotic fluid cell (passage 6) expression of stem cell specific markers OCT-4, SOX2, Rex1, FGF4, and NANOG was confirmed by RT-PCR. Flow cytometric analysis showed that hAFS (passage 10) were positive for CD44, CD29, CD146, STRO1, and CD90 but negative for CD19. Immunocytochemical analysis of hAFS (passage 11) also showed the expression of OCT-4, SSEA-1, CD44, CD29, CD146, STRO1, and CD90, but hAFS were negative for CD19 and CD14. In conclusion, according to the previous studies on other mammalians, hAFS are an appropriate source of pluripotent stem cells. Here, we demonstrated that hAFS have a high expression of stem cell specific marker, including embryonic stem cell marker and mesenchymal stem cell marker. Therefore, amniotic fluid may be a suitable alternative source of multipotent stem cells.

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