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Prostate cancer metastases directly compete with hematopoietic stem cells for occupancy of the stem cell niche

From the Journal of Clinical Investigation

Results from a recent study published in the Journal of Clinical Investigation by Shiozawa et al. from the University of Michigan and Harvard School of Dental Medicine provide new evidence for the mechanisms directing metastases of carcinomas into bone tissue, observed in 70% of patients with breast or prostate cancer and up to 30% of patients with lung, colon, stomach, bladder, uterine, rectal, thyroid or kidney carcinomas. Their work reveals that metastases target the skeleton by taking advantage of signals normally present in the hematopoietic stem cell (HSC) niche that are known to regulate HSC homing, quiescence and self renewal. Using a mouse model of metastasis, the authors demonstrate that metastasised human prostate cancer cells (PCa) directly compete with HSCs for residency within the HSC niche, preventing HSC engraftment by occupying the HSC niche and driving out HSCs into progenitor pools and the peripheral blood by driving HSC terminal differentiation. Further, they demonstrate the co-localisation of PCa cells and HSCs to the endosteal niche of the bone marrow, particularly to Anxa2-expressing osteoblasts (known to play a central role in HSC niche selection), indicating this to be the site of the HSC niche, the exact location and composition of which has been a controversial issue until now. Interestingly, decreasing the HSC niche size by ablating osteoblastic lineage cells decreased PCa parasitisation of the niche. Moreover, the authors were able to mobilize PCa cells out of the HSC niche by using agents known to cause HSCs to reenter the peripheral circulation. This work has identified three potential mechanisms that might be modulated to minimise metastasis of carcinoma cells into bone tissue, opening new possibilities for therapeutic intervention in metastatic cancer.

Announcing the first stem cell translational journal

Durham, NC, April 2011 – AlphaMed Press announces the launch of a major peer-reviewed journal, STEM CELLS Translational Medicine (SCTM), answering an acknowledged need within the research and clinical communities for comprehensive coverage of stem cell science, stem cell-based regenerative medicine and tissue engineering, stem cell-based predictive toxicology, and cancer stem cell investigation.

STEM CELLS Translational Medicine will publish high-impact, peer-reviewed articles that will significantly advance the clinical utilization of stem cell molecular and cellular biology by bridging stem cell research and clinical trials. In addition to original manuscripts, case studies, and commentaries this unique journal will encourage researchers to submit data from their negative clinical trials for publication to rapidly share results that other researchers may find valuable.

Genetic Instability in Induced Pluripotent Stem Cells: One Step Forward in Understanding, Two Steps Back from the Clinic?

Review by Stuart P. Atkinson

Recent studies in embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) biology have turned from comparative studies at the RNA and chromatin level to focus on what’s happening at the DNA level (See iPSC don´t Forget their Origins and Another Blow to the iPSC Field?). Genomic integrity is of course vital for the future use of such pluripotent cells in the clinic; changes at the genomic level can, at best, lead to failure of transplanted cell function, and in the worst case potentially lead to tumorigenesis. This review hopes to condense some of the recent high impact papers which have studied genomic alteration in iPSC in great detail.

Genetic Instability in Induced Pluripotent Stem Cells: One Step Forward in Understanding, Two Steps Back from the Clinic?

Review by Stuart P. Atkinson

Recent studies in embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) biology have turned from comparative studies at the RNA and chromatin level to focus on what’s happening at the DNA level (See iPSC don´t Forget their Origins and Another Blow to the iPSC Field?). Genomic integrity is of course vital for the future use of such pluripotent cells in the clinic; changes at the genomic level can, at best, lead to failure of transplanted cell function, and in the worst case potentially lead to tumorigenesis. This review hopes to condense some of the recent high impact papers which have studied genomic alteration in iPSC in great detail.

Production of Mouse Embryonic Stem Cell Lines from Maturing Oocytes by Direct Conversion of Meiosis into Mitosis

From the March 2011 Issue of Stem Cells

Paper Commentary by Stuart P. Atkinson

Induced pluripotent stem cells (iPSC) have the potential to provide a patient specific source of cells that can be used in cellular therapy. However doubts about their similarity to embryonic stem cells (ESCs) have arisen, both at the gene expression and epigenetic level, and also with their initial differentiation capabilities and the capacity of the differentiated cells to function properly. So what other potential sources do we have? Currently derived human ESC lines (hESC) may not have the genetic diversity required, whilst derivation of additional hESC lines has associated ethical (and funding) problems. Meanwhile, hESC-derivation from somatic cell nuclear transfer (SCNT) has yet to yield results and does not look likely to in the short term. For many, iPSCs still represent the future of stem cell research and stem cell derivation. However, another source of pluripotent cells which are often overlooked may be available, in the form of parthenogenetic stem cells. Parthenogenetic ESCs are derived from activated oocytes at the metaphase II stage and could provide a patient specific source of ESCs for the donor female, and perhaps relatives of the said donor (Hikichi et al. and Kim et al.). However donated oocytes at this stage of development are generally used in assisted reproduction and are therefore of scarce availability, a problem also associated with SCNT. However, Josef Fulka Jr’s group at the Institute of Animal Science, Pratelstvi, Prague have now demonstrated a new method of creating parthenogenetic ESCs from metaphase I oocytes, which are often discarded during the course of IVF, by using Butyrolactone I (BL1). This study (Fulka et al.) is presented in the March Edition of Stem Cells.

Production of Mouse Embryonic Stem Cell Lines from Maturing Oocytes by Direct Conversion of Meiosis into Mitosis

From the March 2011 Issue of Stem Cells

Paper Commentary by Stuart P. Atkinson

Induced pluripotent stem cells (iPSC) have the potential to provide a patient specific source of cells that can be used in cellular therapy. However doubts about their similarity to embryonic stem cells (ESCs) have arisen, both at the gene expression and epigenetic level, and also with their initial differentiation capabilities and the capacity of the differentiated cells to function properly. So what other potential sources do we have? Currently derived human ESC lines (hESC) may not have the genetic diversity required, whilst derivation of additional hESC lines has associated ethical (and funding) problems. Meanwhile, hESC-derivation from somatic cell nuclear transfer (SCNT) has yet to yield results and does not look likely to in the short term. For many, iPSCs still represent the future of stem cell research and stem cell derivation. However, another source of pluripotent cells which are often overlooked may be available, in the form of parthenogenetic stem cells. Parthenogenetic ESCs are derived from activated oocytes at the metaphase II stage and could provide a patient specific source of ESCs for the donor female, and perhaps relatives of the said donor (Hikichi et al. and Kim et al.). However donated oocytes at this stage of development are generally used in assisted reproduction and are therefore of scarce availability, a problem also associated with SCNT. However, Josef Fulka Jr’s group at the Institute of Animal Science, Pratelstvi, Prague have now demonstrated a new method of creating parthenogenetic ESCs from metaphase I oocytes, which are often discarded during the course of IVF, by using Butyrolactone I (BL1). This study (Fulka et al.) is presented in the March Edition of Stem Cells.

Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Mitochondrial function is understood to play a key role in the ageing process and mitochondrial dysfunction underlies the pathophysiology of various diseases. Whilst much attention has focused on the role of the genetic and epigenetic state on cell function and differentiation in stem cells, little work thus far has addressed the contribution of cell metabolism in stem cell function and activity. New results reported in the March edition of Stem Cells by Mandal et al. from the University of California and Indian Institute of Science Education and Research, now begin to reveal the relationship between the mitochondria and stem cell proliferation, differentiation and tumorigenesis.

Mitochondrial Function Controls Proliferation and Early Differentiation Potential of Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Carla Mellough

Mitochondrial function is understood to play a key role in the ageing process and mitochondrial dysfunction underlies the pathophysiology of various diseases. Whilst much attention has focused on the role of the genetic and epigenetic state on cell function and differentiation in stem cells, little work thus far has addressed the contribution of cell metabolism in stem cell function and activity. New results reported in the March edition of Stem Cells by Mandal et al. from the University of California and Indian Institute of Science Education and Research, now begin to reveal the relationship between the mitochondria and stem cell proliferation, differentiation and tumorigenesis.

Genome-wide Studies reveal that LIN28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Stuart P. Atkinson

The RNA binding protein LIN28 (or LIN28A) is highly expressed in human embryonic stem cells (hESCs) and is often used in the generation of induced pluripotent stem cells (iPSCs) (Yu et al.). It is known to play a role in inhibiting the maturation and promoting the degradation of the Let7 family of microRNAs which are known to promote the expression of genes involved in differentiation. However multiple Let7 independent roles for LIN28 have also been observed, and have prompted a study from the laboratory of Yingqun Huang at the Yale Stem Cell Center presented in the March edition of Stem Cells.

Genome-wide Studies reveal that LIN28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells

From the March 2011 Issue of Stem Cells

Paper Commentary by Stuart P. Atkinson

The RNA binding protein LIN28 (or LIN28A) is highly expressed in human embryonic stem cells (hESCs) and is often used in the generation of induced pluripotent stem cells (iPSCs) (Yu et al.). It is known to play a role in inhibiting the maturation and promoting the degradation of the Let7 family of microRNAs which are known to promote the expression of genes involved in differentiation. However multiple Let7 independent roles for LIN28 have also been observed, and have prompted a study from the laboratory of Yingqun Huang at the Yale Stem Cell Center presented in the March edition of Stem Cells.

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