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Similar Human iPSC and ESC Chromatin States Suggests Usefulness in Regenerative Medicine

From Cell Stem Cell

Research published in the 6th August edition of Cell Stem Cell suggests that human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) may be more similar than previously thought. This research, from the laboratory of Richard A. Young shows that genome-wide maps of H3K4me3 and H3K27me3 in a panel of hESC and hiPSCs showed little differences and similar gene expression profiles. Within the same edition of Cell Stem Cell, a study from the laboratory of James B. Cooper suggests that many changes between hESC and hiPSC observed may be due to the micro-environmental context in which the cells were grown and, perhaps, analysed. Also from the same edition comes a report from Kathrin Plath and William E. Lowry who discuss the meta-analyses employed when studying expression in hESC vs. hiPSCs in order to optimize “best practice” to minimize laboratory-borne differences between these cell types.

However this does contradict recent papers which suggest that iPSC, when at low passage, are transcriptionally and epigenetically different (see recent Editorial - iPSC don´t Forget their Origins) and also exhibit differences at imprinted genes at later passages. Perhaps an expansion to a panel of histone modifications and including DNA methylation and miRNA analysis may give us a clearer story of the relative similarities and differences between hESC and hiPSC.

References

Cell Stem Cell
Chromatin Structure and Gene Expression Programs of Human Embryonic and Induced Pluripotent Stem Cells
Matthew G. Guenther et al.

Cell Stem Cell
Lab-Specific Gene Expression Signatures in Pluripotent Stem Cells
Aaron M. Newman and James B. Cooper

Cell Stem Cell
Molecular Analyses of Human Induced Pluripotent Stem Cells and Embryonic Stem Cells
Mark H. Chin, Matteo Pellegrini et al.

Cell Stem Cell News Preview

Recreating Pluripotency?
Kyle M. Loh and Bing Lim

An Eye for an Eye: Long Term Clinical Success with Limbal Stem Cells

From Nature

The long term success of limbal stem cell (LSC) therapy to treat blindness has been highlighted in an article from Nature News & Views. LSCs reside in the narrow zone between the cornea and conjunctiva and are essential for corneal clarity and the efficient transmission and focus of light onto the retina. However ocular burns or infection can deplete LSCs, causing limbal stem cell deficiency (LSCD). Subsequent conjunctival cell invasion forms an epithelial layer over the cornea leading to corneal vascularisation, inflammation, stromal scarring and blindness. There are 8 million new cases worldwide of this painful, blinding disease each year. A recent article published in the New England Journal of Medicine by Pellegrini, De Luca and colleagues1 reports the successful treatment of LSCD following corneal burn by treatment of the affected eye with LSCs taken from the healthy, neighbouring eye. This follows the success of the first reported clinical trial of this therapy last year at the North East England Stem Cell Institute (NESCI) in Newcastle (UK), where eight patients with LSCD were treated using their own limbal stem cells, without the need for immunosuppression.2 This technique, first developed by Pellegrini’s group in 1997,3 was modified by the Newcastle group to be completely animal free by expanding patients limbal stem cells on human amniotic membrane2 instead of mouse 3T3 cells used in the original study.1,3 In all patients LSCD was successfully reversed with significant improvement in visual acuity and corneal capacity over the 19 month trial period. Pellegrini, De Luca and colleagues1 now report the results of their impressive study of 112 patients with LSCD with a follow-up of up to 10 years, which demonstrates the permanent reconstitution of healthy, self-renewing corneal epithelium in 78% of patients. Further, the authors found that treatment with limbal cultures in which p63-bright cells constituted more than 3% of colony forming cells was associated with the best clinical outcome. This work not only provides further evidence for the long term viability and success of this treatment, but equips clinicians with a powerful diagnostic tool to predict the long term transplant outcome in patients receiving autologous LSC grafts.

References

1. Rama P, Matuska S, Paganoni G et al., Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010 363(2):147-55.

2. Kolli S, Ahmad S, Lako M, Figueiredo F. Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Stem Cells. 2010 28(3):597-610.

3. Pellegrini G, Traverso CE, Franzi AT et al., Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet. 1997 349(9057):990-3.

Also see related items from The Times and Newcastle University.

An Eye for an Eye: Long Term Clinical Success with Limbal Stem Cells

From Nature

The long term success of limbal stem cell (LSC) therapy to treat blindness has been highlighted in an article from Nature News & Views. LSCs reside in the narrow zone between the cornea and conjunctiva and are essential for corneal clarity and the efficient transmission and focus of light onto the retina. However ocular burns or infection can deplete LSCs, causing limbal stem cell deficiency (LSCD). Subsequent conjunctival cell invasion forms an epithelial layer over the cornea leading to corneal vascularisation, inflammation, stromal scarring and blindness. There are 8 million new cases worldwide of this painful, blinding disease each year. A recent article published in the New England Journal of Medicine by Pellegrini, De Luca and colleagues1 reports the successful treatment of LSCD following corneal burn by treatment of the affected eye with LSCs taken from the healthy, neighbouring eye. This follows the success of the first reported clinical trial of this therapy last year at the North East England Stem Cell Institute (NESCI) in Newcastle (UK), where eight patients with LSCD were treated using their own limbal stem cells, without the need for immunosuppression.2 This technique, first developed by Pellegrini’s group in 1997,3 was modified by the Newcastle group to be completely animal free by expanding patients limbal stem cells on human amniotic membrane2 instead of mouse 3T3 cells used in the original study.1,3 In all patients LSCD was successfully reversed with significant improvement in visual acuity and corneal capacity over the 19 month trial period. Pellegrini, De Luca and colleagues1 now report the results of their impressive study of 112 patients with LSCD with a follow-up of up to 10 years, which demonstrates the permanent reconstitution of healthy, self-renewing corneal epithelium in 78% of patients. Further, the authors found that treatment with limbal cultures in which p63-bright cells constituted more than 3% of colony forming cells was associated with the best clinical outcome. This work not only provides further evidence for the long term viability and success of this treatment, but equips clinicians with a powerful diagnostic tool to predict the long term transplant outcome in patients receiving autologous LSC grafts.

References

1. Rama P, Matuska S, Paganoni G et al., Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010 363(2):147-55.

2. Kolli S, Ahmad S, Lako M, Figueiredo F. Successful clinical implementation of corneal epithelial stem cell therapy for treatment of unilateral limbal stem cell deficiency. Stem Cells. 2010 28(3):597-610.

3. Pellegrini G, Traverso CE, Franzi AT et al., Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. Lancet. 1997 349(9057):990-3.

Also see related items from The Times and Newcastle University.

SC NIH

Durham, North Carolina, August 27, 2010 — The Journal STEM CELLS® has published many important and exciting achievements in the field of stem cells during its twenty-eight year history. Through scientific discovery, the Journal reports on both adult and human embryonic stem cells (hESCs). The Journal believes that the scientific community benefits from research on all stem cell types in order to maximize our basic biological knowledge and our ability to fight debilitating human diseases. Therefore, we applauded the US Food and Drug Administration (FDA) in July when it approved the first authorized clinical trials using hESCs to treat spinal cord injury.  This decision encouraged researchers, clinicians, and patients alike.

iPSC don´t Forget their Origins.

By Stuart P. Atkinson

Our latest news section recently highlighted the publication of two advance articles from Nature and Nature Biotechnology which suggest that induced pluripotent stem cells (iPSCs) retain memories of the differentiated cell type from which they were derived; their cell of origin. Understandably, this raises several questions about the comparability of iPSCs to human embryonic stem cells (hESCs), particularly since the concept of epigenetic memory has arisen in the production of cloned mammals using somatic cell nuclear transfer. Given the importance of this topic, here we provide a more in-depth discussion of these two articles.

SC NIH

Durham, North Carolina, August 27, 2010 — The Journal STEM CELLS® has published many important and exciting achievements in the field of stem cells during its twenty-eight year history. Through scientific discovery, the Journal reports on both adult and human embryonic stem cells (hESCs). The Journal believes that the scientific community benefits from research on all stem cell types in order to maximize our basic biological knowledge and our ability to fight debilitating human diseases. Therefore, we applauded the US Food and Drug Administration (FDA) in July when it approved the first authorized clinical trials using hESCs to treat spinal cord injury.  This decision encouraged researchers, clinicians, and patients alike.

iPSC don´t Forget their Origins.

By Stuart P. Atkinson

Our latest news section recently highlighted the publication of two advance articles from Nature and Nature Biotechnology which suggest that induced pluripotent stem cells (iPSCs) retain memories of the differentiated cell type from which they were derived; their cell of origin. Understandably, this raises several questions about the comparability of iPSCs to human embryonic stem cells (hESCs), particularly since the concept of epigenetic memory has arisen in the production of cloned mammals using somatic cell nuclear transfer. Given the importance of this topic, here we provide a more in-depth discussion of these two articles.

A Nucleolar Link to Pluripotency and Reprogramming?

By Stuart P. Atkinson

Delineation of the mechanisms by which embryonic stem cells (ESC) remain pluripotent and maintain the ability to differentiate across all germ lineages has attracted many studies which altogether can be consolidated into an information network which combines transcription factors, chromatin and DNA modifications, small RNAs and signal transduction pathways. Analyses of the interactions within this network will unravel the mechanisms underlying these properties into something we can begin to understand and appreciate. Such analysis may also lend itself to the discovery of new ways to produce safer and better induced pluripotent stem cells (iPSC) reprogrammed from somatic cells. In order to uncover new mechanisms underlying pluripotency and lineage specification, researchers from the laboratory of Sheng Ding have taken a new approach, using individually-arrayed cDNA libraries representing more than 30,000 clones, for the identification of new genes which affect pluripotency. This new study is published online in Stem Cells.

A Nucleolar Link to Pluripotency and Reprogramming?

By Stuart P. Atkinson

Delineation of the mechanisms by which embryonic stem cells (ESC) remain pluripotent and maintain the ability to differentiate across all germ lineages has attracted many studies which altogether can be consolidated into an information network which combines transcription factors, chromatin and DNA modifications, small RNAs and signal transduction pathways. Analyses of the interactions within this network will unravel the mechanisms underlying these properties into something we can begin to understand and appreciate. Such analysis may also lend itself to the discovery of new ways to produce safer and better induced pluripotent stem cells (iPSC) reprogrammed from somatic cells. In order to uncover new mechanisms underlying pluripotency and lineage specification, researchers from the laboratory of Sheng Ding have taken a new approach, using individually-arrayed cDNA libraries representing more than 30,000 clones, for the identification of new genes which affect pluripotency. This new study is published online in Stem Cells.

hES say G1-yeS!

By Stuart P. Atkinson

The potential applications of human embryonic stem cells (hESC) in regenerative medicine are far reaching, but the need for large numbers of these cells requires prolonged in vitro culture which can lead to the accumulation of unwanted genetic changes and potentially, tumorigenicity.

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