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Molecular Control of Induced Pluripotency- Free Review

Jacob Blumenthal's insight:

In this new open-access review, Thorold W. Theunissen, and Rudolf Jaenisch from the Whitehead Institute review recent advances in epigenetic reprogramming to pluripotency with a focus on the main molecular regulators. The authors "examine the trajectories connecting somatic and pluripotent cells, examine genetic and chemical methodologies for inducing pluripotency, the role of endogenous master transcription factors in establishing the pluripotent state, and functional interactions between reprogramming factors and epigenetic regulators".  

This free review gives a very good overview on the molecular aspects of pluripotency induction and reprogramming by leading researchers of the field. Highly recommended!

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Scientific Breakthrough as Artificial Blood is Created from Stem Cells

Scientific Breakthrough as Artificial Blood is Created from Stem Cells | Stem Cells & Tissue Engineering | Scoop.it
Mass production of human blood could become reality as artificial blood is tested on patients for the first time.
Jacob Blumenthal's insight:

British researchers have announced that after 4 years of research their Blood Pharma programme has made enough progress turning stem cells into red blood cells to move to clinical trials by late 2016. The researchers use both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) to generate blood cells in-vitro. They differentiate them into red blood cells, and expand their number in culture. The last differentiation stage is when the  developing blood cells eject their DNA to adopt the enucleated state characteristic of red blood cells.

Learn more about blood development and related stem cell differentiation protocols:

http://discovery.lifemapsc.com/in-vivo-development/blood

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NIH stem-cell programme closes

NIH stem-cell programme closes | Stem Cells & Tissue Engineering | Scoop.it
Director resigns as just one clinical-trial award is made.
Jacob Blumenthal's insight:

A news article published today in Nature, reveals that stem-cell biologist Mahendra Rao who was the director of CRM, left the NIH on 28 March. Established in 2010, CRM's goal was to promote and develop induced pluripotent stem (iPS) cells (adult cells that have been converted into embryonic-like stem cells) —based therapies. 

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Patient stem cells help identify common problem in ALS

Patient stem cells help identify common problem in ALS | Stem Cells & Tissue Engineering | Scoop.it
Harvard stem cell scientists have discovered that a recently approved medication for epilepsy may possibly be a meaningful treatment for amyotrophic lateral sclerosis (ALS)—Lou Gehrig's disease, a uniformly fatal neurodegenerative disorder. The researchers are now collaborating with Massachusetts ...
Jacob Blumenthal's insight:

In two papers, published in Cell Reports, and in Cell Stem Cell, researchers used induced pluripotent stem cells (iPSC) derived from Amyotrophic Lateral Sclerosis (ALS) patients cells to study  aberrant molecular mechanisms related to ALS  in-vitro. In the first paper, researchers from the labs of Kevin Eggan and Clifford Woolf found that iPSC-derived motor neurons from ALS patients are hyperexcitable compared to controls, and that the drug Retigabine,  which has recently been approved as an anticonvulsive, could rescues the hyperexcitability phenotype in multiple ALS variants.

In the second paper, researchers from the lab of Su-Chun Zhang found that neurofilament aggregation is an early phenotype of ALS, and that correction of  neurofilament expression, mitigates axonal degeneration in ALS motor neurons.

http://www.cell.com/cell-reports/abstract/S2211-1247(14)00197-1

http://www.cell.com/cell-stem-cell/abstract/S1934-5909(14)00055-1

 

Learn about motor neurons development, pathologies, gene expression and related motor neurons derivation protocols:

http://discovery.lifemapsc.com/in-vivo-development/motor-neurons

 

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Cell Stem Cell - Therapeutic Translation of iPSCs for Treating Neurological Disease

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This review, published on June 2013 discuss the importance of reprogramming technology for modeling and treating neurological and psychiatric diseases such as Alzheimer’s and Parkinson’s diseases, autism and schizophrenia. The review is free, and part of the "Feature Five" review collection of Cell Stem Cell journal.
-- To learn more about stem cells, regenerative medicine and developmental biology visit:  http://discovery.lifemapsc.com/

 

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Carlos Garcia Pando's curator insight, March 7, 2014 6:45 AM

Absolutly fantastic. 

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Cell Reports - NPTX1 Regulates Neural Lineage Specification from Human Pluripotent Stem Cells

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Researchers from the Neural Stem Cell Institute have discovered that the secreted protein  NPTX1 plays a key role in neural lineage specification. They found that NPTX1 is rapidly upregulated during neural induction from human pluripotent stem cells (hPSCs) and that by  contolling its expression levels it is possible to reduce or initiate neural lineage commitment.

Full paper: http://www.cell.com/cell-reports/fulltext/S2211-1247(14)00043-6#Summary


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Stem Cells For Darwin: How iPSCs Can Explore Evolution

Stem Cells For Darwin: How iPSCs Can Explore Evolution | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

This short new article in Forbes, discuss a paper recently published in Nature journal where researchers generated induced pluripotent stem cells (iPSCs) from humans, chimpanzees and  bonobos. They investigated the regulation of long interspersed nuclear element-1 (LINE-1 or L1) transposons in order to understand why humans as a species have such limited genetic variation, compared to the non-human primates (NHP) most closely related to them.

Full paper: 

http://www.nature.com/nature/journal/v503/n7477/full/nature12686.html


Learn more about embryonic development and stem cells:

http://discovery.lifemapsc.com/

 


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For the first time: new hair fom stem cells

Jacob Blumenthal's insight:

Researchers from the University of Pennsylvania have developed a novel method for generation of epithelial stem cells (EpSCs)  from human pluripotent stem cells. These EpSCs are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays.

http://www.nature.com/ncomms/2014/140128/ncomms4071/full/ncomms4071.html

 

Learn about hair development:

http://discovery.lifemapsc.com/in-vivo-development/hair

 

Join my Facebook group for more stem cell scoops:

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Carlos Garcia Pando's comment, January 31, 2014 11:30 AM
After several millenia of magic cures and useless remedies I can't believe all those bold headed people will at last have a chance.
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Pluripotent stem cells in regenerative medicine: challenges and recent progress : Nature Reviews Genetics

Pluripotent stem cells in regenerative medicine: challenges and recent progress : Nature Reviews Genetics | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

A new review by Viviane Tabar & Lorenz Studer discuss recent achievements  in directed differentiation of pluripotent stem cells,  new technologies that have facilitated the success of pluripotent stem cells therapies and the remaining obstacles on the road towards developing pluripotent stem cell-based  therapies.

http://www.nature.com/nrg/journal/v15/n2/abs/nrg3563.html?lang=en?WT.ec_id=NRG-201402

 

To learn more about stem cells:

http://discovery.lifemapsc.com/stem-cell-differentiation

 

 

 

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David O'Connell's curator insight, February 8, 2014 10:31 AM
Jacob Blumenthal's insight:

A new review by Viviane Tabar & Lorenz Studer discuss recent achievements  in directed differentiation of pluripotent stem cells,  new technologies that have facilitated the success of pluripotent stem cells therapies and the remaining obstacles on the road towards developing pluripotent stem cell-based  therapies.

http://www.nature.com/nrg/journal/v15/n2/abs/nrg3563.html?lang=en?WT.ec_id=NRG-201402

 

To learn more about stem cells:

http://discovery.lifemapsc.com/stem-cell-differentiation

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Cell Stem Cell - Human Pluripotent Stem Cell Culture: Considerations for Maintenance, Expansion, and Therapeutics

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In this protocol review, the authors describe and compare  several methods for culturing of human pluripotent stem cells.

 

Learn more about stem cell differentiation protocols:

http://discovery.lifemapsc.com/

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From pluripotent stem cells to kidneys in a dish

From pluripotent stem cells to kidneys in a dish | Stem Cells & Tissue Engineering | Scoop.it

http://discovery.lifemapsc.com/in-vivo-development/kidney

Jacob Blumenthal's insight:

Two new papers, published in Cell Stem Cell, and Nature Cell Biology magazines, describes protocols for generation of kidney structures from human pluripotent stem cells.

http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb2894.html

http://www.cell.com/cell-stem-cell/abstract/S1934-5909(13)00501-8

 

To learn about the embryonic development, anatomical compartments, gene expression of the kidney and related stem cell differentiation protocols:

http://discovery.lifemapsc.com/in-vivo-development/kidney

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Cell Stem Cell - Integrating Human Pluripotent Stem Cells into Drug Development - Cell Stem Cell

Jacob Blumenthal's insight:

This review, published on June in Cell Stem Cell journal, is now freely available, as part of the "Featured Five Reviews" of the Journal. It describes how researchers can use human pluripotent stem cells for drug discovery purposes.

http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(13)00204-X

 

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A fully defined and scalable 3D culture system for human pluripotent stem cell expansion and differentiation

Jacob Blumenthal's insight:

A new paper in PNAS describes a novel 3D culturing system for culturing and expansion of pluripotent stem cells. It is based on a unique hydrogel that allows  to control the exact composition of the growth environment, free of any human- or animal-derived factors, and entailing only recombinant protein factors.


To learn about stem cells, embryonic development, and regenerative medicine:

http://discovery.lifemapsc.com/

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Goodbye iPSCs Hello Cloning?

In what looks like a major scientific breakthrough, researchers reported in Cell Stem Cell a new technique for producing patient-specific embryonic stem cells via somatic-cell nuclear transfer (SCNT)
Jacob Blumenthal's insight:

In what looks like a major scientific breakthrough, researchers reported in Cell Stem Cell a new technique for producing patient-specific embryonic stem cells via somatic-cell nuclear transfer (SCNT). The researchers used a nuclear transfer method, previously developed by reproductive biologist Shoukhrat Mitalipov of Oregon Health and Science University, to fuse between fibroblast cells of 35- and 75-year-old males and enucleated oocytes. The fused egg, now containing the DNA of the mature fibroblasts, started to divide in response to a stimulation and within five or six days it develops into an embryo shaped like a hollow sphere, which contained embryonic stem cells in its interior. Researchers believe that the crucial step in the process is the waiting time before triggering the egg to start dividing. In this study the researchers waited two hours. This time window is probably crucial to initiate reprogramming events of the mature DNA in the egg, prior to its divisions.

This amazing achievement will allow to generate patient specific embryonic stem cells from the patient own mature cells and to use them in various cell therapy approaches. Unlike induced pluripotent stem cell (iPS) techniques, this procedure does not require any plasmids or viral reprogramming systems, and therefore its much safer. However, we shall wait until more labs and researchers will confirm that SCNT in humans can be reproduced, before throwing away any "old" reprogramming methods.

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Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells: Cell Stem Cell

Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells: Cell Stem Cell | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

A new paper in Cell Stem Cell describes a novel protocol for generation of stable immortalized megakaryocyte progenitor cell lines (imMKCLs) from human pluripotent stem cells (hPSC). The researchers derived imMKCLs from PSC-derived hematopoietic progenitors by overexpression of BMI1, BCL-XL , and c-MYC.

The derived  imMKCLs  have robust expansion capacity and can differentiate into mature megakaryocytes that release functional platelets. These characteristics makes them an ideal inexhaustible source of hPSC-derived platelets for clinical applications. 


Learn more about stem cells and differentiation protocols:

http://discovery.lifemapsc.com/stem-cell-differentiation


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Alzheimer’s research team employs stem cells to understand disease processes and study new treatment

Alzheimer’s research team employs stem cells to understand disease processes and study new treatment | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

Researchers from the Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School have generated  induced pluripotent stem cell (iPSC) lines from patients harboring the London familial AD (fAD) amyloid precursor protein (APP) mutation (V717I). They found that during differentiation of the iPSC towards neuronal fate, APP expression and levels of Aβ increase dramatically. In addition, an increase in levels of total and phosphorylated Tau was also observed in neurons with the APPV717I mutation. Treating the neurons early in culture with Aβ-specific antibodies, reversed the phenotype of increased total Tau levels.

http://www.ncbi.nlm.nih.gov/pubmed/24524897



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A*STAR scientists create stem cells from drop of blood - Channel NewsAsia

A*STAR scientists create stem cells from drop of blood - Channel NewsAsia | Stem Cells & Tissue Engineering | Scoop.it

Scientists at A*STAR's Institute of Molecular and Cell Biology (IMCB) have developed a method to generate human induced pluripotent stem cells (hiPSCs) from a single drop of finger-pricked blood.

Jacob Blumenthal's insight:

Researchers from  A*STAR's Institute of Molecular and Cell Biology (IMCB)  have developed a method for derivation of induced pluripotent stem cells (iPSCs) from a single drop of blood. The main achievement in this research is that the volume of a single blood is sufficient for the production of iPSCs. This approach will make the establishement of iPSCs banks easier .

Learn more about iPSCs:

http://discovery.lifemapsc.com/stem-cell-differentiation

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Building a Kidney: Using Pluripotent Stem Cells to Differentiate Kidney Structures

Building a Kidney:  Using Pluripotent Stem Cells to Differentiate Kidney Structures | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

Kidneys develop from the intermediate metanephros (IM), which gives rise to the metanephric mesenchyme (MM) and the ureteric bud (UB). The MM forms the glomerulus and the renal tubules while the UB differentiates into the collecting duct. Reciprocal interactions between the MM and the UB are necessary for development of the kidney. Both the MM and the UB contain stem cells, however, once these cells are removed from their respective niches, they spontaneously terminally differentiate, rendering, creation of kidney structures in vitro very difficult. Recently, two papers (from Nishinakamura and Little's research groups) describe the use ... (Read the full story in the newsletter).

http://us4.campaign-archive1.com/?u=985051700e9649000fa0c0d4a&id=22f09f7211&e=f1b990f7f8

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Yamanaka takes issue with claims STAP cells are safer than iPS option

Yamanaka takes issue with claims STAP cells are safer than iPS option | Stem Cells & Tissue Engineering | Scoop.it
Nobel Prize-winning scientist Shinya Yamanaka, facing reporters in Kyoto, decried 'three misconceptions' about the induced pluripotent stem, or iPS, cells that he developed in relation to STAP cells were recently ...
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Why I’m Sure Testing Induced Stem Cells in Humans Will Be Safe

Why I’m Sure Testing Induced Stem Cells in Humans Will Be Safe | Stem Cells & Tissue Engineering | Scoop.it

Masayo Takahashi is at the Riken Center for Developmental Biology in Kobe, Japan, where she heads the Laboratory for Retinal Regeneration and is planning a pilot safety study using a type of stem cell to treat age-related blindness. Natasha Little: Later this year, you will make history when you begin...

Jacob Blumenthal's insight:

This is an interview with Masayo Takahashi about the first ever human clinical trial of induced pluripotent stem cells (iPSC). In this clinical trial skin cells will be taken from age-related macular degeneration patients, and will be reprogrammed into iPSC. These iPSC will be then differentiated into retinal pigment epithelium (RPE) cells in-vitro. The differentiated cells will be introduced back to the eyes of the patients.

Learn more about RPE cells:

http://discovery.lifemapsc.com/in-vivo-development/eye/retinal-pigmented-epithelium/mature-retinal-pigmented-epithelium-cells


Learn more about stem cells differentiation:

http://discovery.lifemapsc.com/stem-cell-differentiation


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Christopher Duntsch's curator insight, February 7, 2014 3:36 AM

I think it is worthwhile to be more specific with blogs and statements. Stem cells are are not all the same. I would prefer as discussed below "Why I'm sure Testing induced IPSCs will be safe" Most with some background recognize that induced means IPSCs. But likely in blog context very few.

 

Embryonic stem cells have great potential, but tag along issues and concerns. Further, they are not proven as therapeutics in any venue to a such a degree that safety, efficacy, cell pharmacobiolgy are a given and human studies inevitably, even if the issue was not in part FDA restrictions. Generally speaking their role for tissue engineering for a given disease, is not define. What is defined is complete competency for growth and differentiation potential that is unlimited. That is certainly exciting, but that is just a start. Were we discussing a novel cancer drug this early in development it would not even be on the radar. For ESCs it is the potential that lies ahead that generates the excitement.,


Adult stem cells are further along in all aspects including clinical studies and applications. They are indeed safe and there has never been evidence otherwise. These days it seems every nextgen biotech or group is using a every stem cell for every purpose without rationale or basis. Indeed, it sometimes looks like like a mix and match with more approaches then successes. Nonetheless, despite two decades of great researcher that goes by to Weisman et al. in the early 90s, these cells only get the attention they deserve because in the appropriate venue they constantly produce. Stem cells work well when used in tissues from which they were derived. Adult stem cells are a prevent entity. 

 

I have no interest at this time in STAPs and will let others provide the proof of concept with actual R&D and developmental research to put these stem cells on my radar.

 

Regarding IPSCs, biology behind the induction of a human pluriopotent stem cell is indeed remarkable and has led to a much better understanding of underlying biology. On the one hand I think that sometimes we forget that half of why so much excitement revolves around them is the fact that ESCs can be avoided.  This an issue for some because the NIH will not fund ESC research  in general, and thus this bypassed a big problem.  For others because of the ethical issues that exist here given one's respective perspective. But I don't know we can say much about these cell just yet beyond the what we know from early studies and modeling. To think that we can approximate the infinitely complex biology of ESCs is ridiculous. To think that the artificial biology induced in an aged somatic cell with telomere biology associated with aging, with more exposure to toxins and DNA damaging agents simply because it its has been here longer and exposed more frequently (such as sunburns, much less real oncogenic toxins), and to think that he biology itself is definitive, retains the same developmental biology programs and patterns as ESCs of blastocyst development in uteror,  is not possible to say just yet as a historical fact.  

 

In the long term, IPSCs may not be the best choice for regenerative medicine. These stem cells, need years of research, long term outcomes studies, understanding of genomic stabity and phenotypic stability, and simply put much more developmental R&D. I am not putting any negativity into IPSC approaches. I just have always been more comfortable with naturally occurring stem cell sources whose biology is well understood. If one day that meant ESCs research may need to supported in this respect so be it. Time and understanding will get us there eventually. 

 

Nonetheless, I will be glad to see the data begin to stack up from more  and more animal and human studies with IPSCs and the truth of what lies in the future for IPSCs is in theses studies, not in opinons.

 

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Stem Cell Reports - Characterization of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cell Sheets Aiming for Clinical Application

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Researchers generated retinal pigment epithelial (RPE) cell sheets from human pluripotent stem cells under optimized conditions, to meet clinical use requirements. These RPE cells expressed specific RPE markers and were further used in transplantation experiments in animal models.

http://www.cell.com/stem-cell-reports/abstract/S2213-6711(13)00175-6

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http://discovery.lifemapsc.com/stem-cell-differentiation

 

 

 

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iPSCs used to model disease causing abnormal bone growth | Stem Cells Freak

iPSCs used to model disease causing abnormal bone growth | Stem Cells Freak | Stem Cells & Tissue Engineering | Scoop.it
Researchers use induced pluripotent stem cells to model Fibrodysplasia ossificans progressiva.
Jacob Blumenthal's insight:

Researchers from Researchers from the University of California - San Francisco developed an induced pluripotent stem cell (iPSC) line from  fibrodysplasia ossificans progressiva (FOP) patient. In this rare disease, muscles and tendons progressively turn into bone. When differentiated into bone tissue, FOP iPS cells exhibited an increase in mineralization and enhanced chondrogenesis in vitro. 

 

To read the full article: http://www.ojrd.com/content/8/1/190

 

Learn about bone development: http://discovery.lifemapsc.com/in-vivo-development/bone


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Induced pluripotent stem cells by Rudolf Jaenisch

Induced pluripotent stem cells by Rudolf Jaenisch | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

Prof. Rudolf Jaenisch on the discovery of iPS cells, their epigenetic state and their therapeutical potential.

Learn more about stem cells and differentiation protocols:

http://discovery.lifemapsc.com/

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New collaboration combines genomic sequencing and stem cell technology to understand disease

New collaboration combines genomic sequencing and stem cell technology to understand disease | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

A new collaboration between the Harvard Personal Genome Project (PGP), and researchers from the New York Stem Cell Foundation (NYSCF) Research Institute has been announced today. NYCSF researchers will derive induced pluripotent stem cells (iPSC) from samples of patients participating in PGP. These cell lines can then be examined and compared to data gathered by the PGP including whole genomes, medical histories, body microbiomes and hundreds of other traits from over 3,000 participants. 

 

To learn about stem cells and related differentiation protocols:

http://discovery.lifemapsc.com/

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Scientists make lung cells from human stem cells

Scientists make lung cells from human stem cells | Stem Cells & Tissue Engineering | Scoop.it
Jacob Blumenthal's insight:

Researchers from the  Columbia University Medical Center, published a new paper in Nature Bitechnology, describing a novel method for generation of functional lung cells from pluripotent stem cells. Their highly-efficient differentiation method resulted in the formation of clara, ciliated, type I and type II alveolar epithelial cells.

A link to the paper:

 http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.2754.html

 

To learn about the embryonic development of the lung and realted stem cell protocols: 

http://discovery.lifemapsc.com/in-vivo-development/lung

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