Inquirer.net

Approaching a decades-old goal: Making blood stem cells from patients' own cells Science Daily ... lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived ... 'Milestone' in quest to make blood cells studiesInquirer.net all 21 news articles »

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Approaching a decades-old goal: Making blood stem cells from patients' own cells - Science Daily

IPS Cell Therapy Comments Off on Approaching a decades-old goal: Making blood stem cells from patients’ own cells – Science Daily | May 18th, 2017

2016.09.20 MEDIAAlvetex wins CV Technology Innovator Awards 2016

ReproCELL is proud to announce its groundbreaking 3D cell culture technology Alvetex has been awarded the Corporate Vision Technology Innovator Award 2016. Read the full interview with Prof. Dr. Stefan Przyborski, ReproCELL Europes Chief Scientific Officer and inventor of Alvetex, here: http://reinnervate.com/reprocell-europe-wins-cv-tech-innovator-awards-2016-alvetex/

We will exhibit and presentat a poster at ISSCR 2016 Annual Meeting, San Francisco, USA. We will like to welcome you to stop by our booth and posters. ISSCR 2016 Annual Meeting URL http://www.isscr.org/home/annual-meeting/san-francisco-2016 Date JUNE 22-25, 2016 Place San Francisco, America Booth: Date JUNE 22-25, 2016 Booth No. 1608 POSTER Date & Time JUNE 22, 2016630PM730PM Poster No. Poster W1093 Title Improvement of human iPS cell-derived hepatocyte functionality using 3D culture systems Presenter ReproCELL, Inc. Zachary Yu Ching Lin Date & Time JUNE 22, 2016730PM830PM Poster No. Poster W2064 Title Non-modified RNAs for the derivation of clinically relevant iPS cell lines from adult []

We make the presentation a poster at 11th International ISSX Meeting at Busan, Korea. Please stop by at our poster if you attend to the meeting. 11th International ISSX Meeting URL http://issxbusan2016.org/ Date June 12-16, 2016 Place Busan, Korea POSTER Date June 15, 201612151300Poster session 2 Location Exhibit Hall (Grand Ballroom 3F) Poster No. P52 Title Stabilized and Enhanced CYP450 Enzyme Activity in Cultured Human Primary Hepatocytes is Conferred by ReproHP Medium Host Sales & Marketing DepartmentPaul CIZDZIEL Wirtz Julia POSTER Date June 15, 201612151300Poster session 2 Location Exhibit Hall (Grand Ballroom 3F) Poster No. P232 Title Improving the prediction of oral bioavailability using fresh []

Webinar: iPSC derived Cells & hiPSC/ES media June 4th 2013 10 AM CEST Please register from here; https://attendee.gotowebinar.com/register/7334590631056470272

ReproCELLs iPS cell technology featured in NHK World news http://www3.nhk.or.jp/nhkworld/english/movie/feature201303211118.html

An article written jointly by Kyoto University and ReproCELL was published in Cell Rep. 2012 Nov 29;2(5):1448-60.. Small Molecule that Promotes Cardiac Differentiation of Human Pluripotent Stem Cells under Defined, Cytokine- and Xeno-free Conditions

ReproCELLs iPS cell business was widely introduced in Japanese TV news on Prof. Shinya Yamanakas Nobel Prize.

ReproCELLs iPS cell-derived cardiomyocytes, neurons and hepatocytes were introduced in Genetic Engineering & Biotechnology News (GEN). Jan 15, 2012 (Vol. 32, No. 2) Stem Cell Applications Hasten into the Clinic

An article in Genetic Engineering & Biotechnology News, Pharmas R&D Focus Shifting to Stem Cells -Investors Interest in These Cells Increases as Scientists Continue to Unleash Their Potential introduces ReproCELLs new cardiotoxicity assay using iPSCs, QTempo, as well as its neural stem cell research. Read the article

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ReproCELL - Stem Cell Innovation

IPS Cell Therapy Comments Off on ReproCELL – Stem Cell Innovation | May 14th, 2017

Cell potency is a cell's ability to differentiate into other cell types.[1][2] The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell which like a continuum begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency and finally unipotency. Potency is taken from the Latin term "potens" which means "having power".

Totipotency is the ability of a single cell to divide and produce all of the differentiated cells in an organism. Spores and zygotes are examples of totipotent cells.[3] In the spectrum of cell potency, totipotency represents the cell with the greatest differentiation potential. Toti comes from the Latin totus which means "entirely".

It is possible for a fully differentiated cell to return to a state of totipotency.[4] This conversion to totipotency is complex, not fully understood and the subject of recent research. Research in 2011 has shown that cells may differentiate not into a fully totipotent cell, but instead into a "complex cellular variation" of totipotency.[5] Stem cells resembling totipotent blastomeres from 2-cell stage embryos can arise spontaneously in the embryonic stem cell cultures[6][7] and also can be induced to arise more frequently in vitro through down-regulation of the chromatin assembly activity of CAF-1.[8]

The human development model is one which can be used to describe how totipotent cells arise.[9] Human development begins when a sperm fertilizes an egg and the resulting fertilized egg creates a single totipotent cell, a zygote.[10] In the first hours after fertilization, this zygote divides into identical totipotent cells, which can later develop into any of the three germ layers of a human (endoderm, mesoderm, or ectoderm), into cells of the cytotrophoblast layer or syncytiotrophoblast layer of the placenta. After reaching a 16-cell stage, the totipotent cells of the morula differentiate into cells that will eventually become either the blastocyst's Inner cell mass or the outer trophoblasts. Approximately four days after fertilization and after several cycles of cell division, these totipotent cells begin to specialize. The inner cell mass, the source of embryonic stem cells, becomes pluripotent.

Research on Caenorhabditis elegans suggests that multiple mechanisms including RNA regulation may play a role in maintaining totipotency at different stages of development in some species.[11] Work with zebrafish and mammals suggest a further interplay between miRNA and RNA binding proteins (RBPs) in determining development differences.[12]

In September 2013, a team from the Spanish national Cancer Research Centre was able for the first time to make adult cells from mice retreat to the characteristics of embryonic stem cells, thereby achieving totipotency.[13]

In cell biology, pluripotency (from the Latin plurimus, meaning very many, and potens, meaning having power)[14] refers to a stem cell that has the potential to differentiate into any of the three germ layers: endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital), or ectoderm (epidermal tissues and nervous system).[15] However, cell pluripotency is a continuum, ranging from the completely pluripotent cell that can form every cell of the embryo proper, e.g., embryonic stem cells and iPSCs (see below), to the incompletely or partially pluripotent cell that can form cells of all three germ layers but that may not exhibit all the characteristics of completely pluripotent cells.

Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes and transcription factors.[16] These transcription factors play a key role in determining the state of these cells and also highlights the fact that these somatic cells do preserve the same genetic information as early embryonic cells.[17] The ability to induce cells into a pluripotent state was initially pioneered in 2006 using mouse fibroblasts and four transcription factors, Oct4, Sox2, Klf4 and c-Myc;[18] this technique, called reprogramming, earned Shinya Yamanaka and John Gurdon the Nobel Prize in Physiology or Medicine 2012.[19] This was then followed in 2007 by the successful induction of human iPSCs derived from human dermal fibroblasts using methods similar to those used for the induction of mouse cells.[20] These induced cells exhibit similar traits to those of embryonic stem cells (ESCs) but do not require the use of embryos. Some of the similarities between ESCs and iPSCs include pluripotency, morphology, self-renewal ability, a trait that implies that they can divide and replicate indefinitely, and gene expression.[21]

Epigenetic factors are also thought to be involved in the actual reprogramming of somatic cells in order to induce pluripotency. It has been theorized that certain epigenetic factors might actually work to clear the original somatic epigenetic marks in order to acquire the new epigenetic marks that are part of achieving a pluripotent state. Chromatin is also reorganized in iPSCs and becomes like that found in ESCs in that it is less condensed and therefore more accessible. Euchromatin modifications are also common which is also consistent with the state of euchromatin found in ESCs.[21]

Due to their great similarity to ESCs, iPSCs have been of great interest to the medical and research community. iPSCs could potentially have the same therapeutic implications and applications as ESCs but without the controversial use of embryos in the process, a topic of great bioethical debate. In fact, the induced pluripotency of somatic cells into undifferentiated iPS cells was originally hailed as the end of the controversial use of embryonic stem cells. However, iPSCs were found to be potentially tumorigenic, and, despite advances,[16] were never approved for clinical stage research in the United States. Setbacks such as low replication rates and early senescence have also been encountered when making iPSCs,[22] hindering their use as ESCs replacements.

Additionally, it has been determined that the somatic expression of combined transcription factors can directly induce other defined somatic cell fates (transdifferentiation); researchers identified three neural-lineage-specific transcription factors that could directly convert mouse fibroblasts (skin cells) into fully functional neurons.[23] This result challenges the terminal nature of cellular differentiation and the integrity of lineage commitment; and implies that with the proper tools, all cells are totipotent and may form all kinds of tissue.

Some of the possible medical and therapeutic uses for iPSCs derived from patients include their use in cell and tissue transplants without the risk of rejection that is commonly encountered. iPSCs can potentially replace animal models unsuitable as well as in-vitro models used for disease research.[24]

Recent findings with respect to epiblasts before and after implantation have produced proposals for classifying pluripotency into two distinct phases: "naive" and "primed".[25] The baseline stem cells commonly used in science that are referred as Embryonic stem cells (ESCs) are derived from a pre-implantation epiblast; such epiblast is able to generate the entire fetus, and one epiblast cell is able to contribute to all cell lineages if injected into another blastocyst. On the other hand, several marked differences can be observed between the pre- and post-implantation epiblasts, such as their difference in morphology, in which the epiblast after implantation changes its morphology into a cup-like shape called the "egg cylinder" as well as chromosomal alteration in which one of the X-chromosomes undergoes random inactivation in the early stage of the egg cylinder, known as X-inactivation.[26] During this development, the egg cylinder epiblast cells are systematically targeted by Fibroblast growth factors, Wnt signaling, and other inductive factors via the surrounding yolk sac and the trophoblast tissue,[27] such that they become instructively specific according to the spatial organization.[28] Another major difference that was observed, with respect to cell potency, is that post-implantation epiblast stem cells are unable to contribute to blastocyst chimeras,[29] which distinguishes them from other known pluripotent stem cells. Cell lines derived from such post-implantation epiblasts are referred to as epiblast-derived stem cells which were first derived in laboratory in 2007; it should be noted, despite their nomenclature, that both ESCs and EpiSCs are derived from epiblasts, just at difference phases of development, and that pluripotency is still intact in the post-implantation epiblast, as demonstrated by the conserved expression of Nanog, Fut4, and Oct-4 in EpiSCs,[30] until somitogenesis and can be reversed midway through induced expression of Oct-4.[31]

Multipotency describes progenitor cells which have the gene activation potential to differentiate into discrete cell types. For example, a multipotent blood stem cell is a hematopoietic celland this cell type can differentiate itself into several types of blood cell types like lymphocytes, monocytes, neutrophils, etc., but cannot differentiate into brain cells, bone cells or other non-blood cell types.

New research related to multipotent cells suggests that multipotent cells may be capable of conversion into unrelated cell types. In another case, human umbilical cord blood stem cells were converted into human neurons.[32] Research is also focusing on converting multipotent cells into pluripotent cells.[33]

Multipotent cells are found in many, but not all human cell types. Multipotent cells have been found in cord blood,[34] adipose tissue,[35] cardiac cells,[36] bone marrow, and mesenchymal stem cells (MSCs) which are found in the third molar.[37]

MSCs may prove to be a valuable source for stem cells from molars at 810 years of age, before adult dental calcification. MSCs can differentiate into osteoblasts, chondrocytes, and adipocytes.[38]

In biology, oligopotency is the ability of progenitor cells to differentiate into a few cell types. It is a degree of potency. Examples of oligopotent stem cells are the lymphoid or myeloid stem cells.[1] A lymphoid cell specifically, can give rise to various blood cells such as B and T cells, however, not to a different blood cell type like a red blood cell.[39] Examples of progenitor cells are vascular stem cells that have the capacity to become both endothelial or smooth muscle cells.

In cell biology, a unipotent cell is the concept that one stem cell has the capacity to differentiate into only one cell type. It is currently unclear if true unipotent stem cells exist. Hepatoblasts, which differentiate into hepatocytes (which constitute most of the liver) or cholangiocytes (epithelial cells of the bile duct), are bipotent.[40] A close synonym for unipotent cell is precursor cell.

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Cell potency - Wikipedia

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Science Daily

Engineering human stem cells to model the kidney's filtration barrier on a chip Science Daily ... of kidney diseases and drug toxicities, and the stem cell-derived kidney podocytes we developed could even offer a new injectable cell therapy approach for regenerative medicine in patients with life-threatening glomerulopathies in the future ...

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Engineering human stem cells to model the kidney's filtration barrier on a chip - Science Daily

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Stem cell therapy is a type of cell therapy wherein cells are introduced into the damaged tissue so as to treat the disorder or the injury. There are a number of medical researchers who believes that the stem cell therapy has the potential to change the treatment of human diseases and reduce the suffering people face when they have a disease. They believe that there are a lot of potential to replace the damaged and diseased tissues in the body without getting the risk of rejections.

The stem cells have the ability to self-renew and also give rise to further generation of cells that can multiply. There are a number of stem cell therapies that do exist but most of them are still in the experimental stages. The treatments are very costly with an exception of bone marrow transplant. However, researchers believe that one day they will be able to develop technologies from embryonic stem cells and also adult stem cells to cure type I diabetes, cancer, Parkinsons disease, cardiac failure, neurological disorders and many more such ailments.

The stem cell therapy however carries its own pros and cons and like any other therapy it cannot be said that the stem cell therapy is an advantageous package. Here are some of the pros and cons of the therapy.

Pros of the stem cell therapy include:

It offers a lot of medical benefits in the therapeutic sectors of regenerative medicine and cloning.

It shows great potential in the treatment of a number of conditions like Parkinsons disease, spinal cord injuries, Alzheimers disease, schizophrenia, cancer, diabetes and many others.

It helps the researchers know more about the growth of human cells and their development.

In future, the stem cell research can allow the scientists to test a number of potential medicines and drugs without carrying out any test on animals and humans. The drug can be tested on a population of cells directly.

The stem cell therapy also allows researchers to study the developmental stages that cannot be known directly through the human embryo and can be used in the treatment of a number of birth defects, infertility problems and also pregnancy loss. A higher understanding will allow the treatment of the abnormal development in the human body.

The stem cell therapy puts into use the cells of the patients own body and hence the risk of rejection can be reduced because the cells belong to the same human body.

The cons of the stem cell therapy include the following:

The use of the stem cells for research involves the destruction of the blastocytes that are formed from the laboratory fertilization of the human egg.

The long term side effects of the therapy are still unknown.

The disadvantage of adult stem cells is that the cells of a particular origin would generate cells only of that type, like brain cells would generate only brain cells and so on.

If the cells used in the therapy are embryonic then the disadvantage is that the cells will not be from the same human body and there are chances of rejection.

The stem cell therapy is still under the process of research and there are a number of things that needs to be established before it used as a treatment line.

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Pros and Cons of Stem Cell Therapy - Health Guidance

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Harvard Gazette

Researchers work to create kidney filtration barrier on a chip ... Harvard Gazette Researchers say their glomerulus-on-a-chip lined by human stem cell-derived kidney cells could help model patient-specific kidney diseases and guide ... and more »

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Researchers work to create kidney filtration barrier on a chip ... - Harvard Gazette

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Shinya Yamanaka ( , Yamanaka Shin'ya?, born September 4, 1962) is a Japanese Nobel Prize-winning stem cell researcher.[1][2][3] He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences(ja) at Kyoto University; as a senior investigator at the UCSF-affiliated J. David Gladstone Institutes in San Francisco, California; and as a professor of anatomy at University of California, San Francisco (UCSF). Yamanaka is also a past president of the International Society for Stem Cell Research (ISSCR).

He received the 2010 BBVA Foundation Frontiers of Knowledge Award in Biomedicine category. Also he received the Wolf Prize in Medicine in 2011 with Rudolf Jaenisch;[6] the Millennium Technology Prize in 2012 together with Linus Torvalds. In 2012 he and John Gurdon were awarded the Nobel Prize for Physiology or Medicine for the discovery that mature cells can be converted to stem cells.[7] In 2013 he was awarded the $3 million Breakthrough Prize in Life Sciences for his work.

Yamanaka was born in Higashisaka Japan in 1962. After graduating from Tennji High School attached to Osaka Kyoiku University,[8] he received his M.D. at Kobe University in 1987 and his PhD at Osaka City University Graduate School in 1993. After this, he went through a residency in orthopedic surgery at National Osaka Hospital and a postdoctoral fellowship at the Gladstone Institute of Cardiovascular Disease, San Francisco.

Afterwards he worked at the Gladstone Institutes in San Francisco, USA and Nara Institute of Science and Technology in Japan. Yamanaka is currently a Professor at Kyoto University, where he directs its Center for iPS Research and Application. He is also a senior investigator at the Gladstone Institutes as well as the director of the Center for iPS Cell Research and Application(ja).[9]

Between 1987 and 1989, Yamanaka was a resident in orthopedic surgery at the National Osaka Hospital. His first operation was to remove a benign tumor from his friend Shuichi Hirata, a task he could not complete after one hour when a skilled surgeon would have taken ten minutes or so. Some seniors referred to him as "Jamanaka", a pun on the Japanese word for obstacle.[10]

From 1993 to 1996, he was at the Gladstone Institute of Cardiovascular Disease. Between 1996 and 1999, he was an assistant professor at Osaka City University Medical School, but found himself mostly looking after mice in the laboratory, not doing actual research.[10]

His wife advised him to become a practicing doctor, but instead he applied for a position at the Nara Institute of Science and Technology. He stated that he could and would clarify the characteristics of embryonic stem cells, and this can-do attitude won him the job. From 19992003, he was an associate professor there, and started the research that would later win him the 2012 Nobel Prize. He became a full professor and remained at the institute in that position from 20032005. Between 2004 and 2010, Yamanaka was a professor at the Institute for Frontier Medical Sciences.[11] Currently, Yamanaka is the director and a professor at the Center for iPS Cell Research and Application at Kyoto University.

In 2006, he and his team generated induced pluripotent stem cells (iPS cells) from adult mouse fibroblasts.[1] iPS cells closely resemble embryonic stem cells, the in vitro equivalent of the part of the blastocyst (the embryo a few days after fertilization) which grows to become the embryo proper. They could show that his iPS cells were pluripotent, i.e. capable of generating all cell lineages of the body. Later he and his team generated iPS cells from human adult fibroblasts,[2] again as the first group to do so. A key difference from previous attempts by the field was his team's use of multiple transcription factors, instead of transfecting one transcription factor per experiment. They started with 24 transcription factors known to be important in the early embryo, but could in the end reduce it to 4 transcription factors Sox2, Oct4, Klf4 and c-Myc.[1]

Yamanaka practiced judo (2nd Dan black belt) and played rugby as a university student. He also has a history of running marathons. After a 20-year gap, he competed in the inaugural Osaka Marathon in 2011 as a charity runner with a time of 4:29:53. He also took part in the 2012 Kyoto Marathon to raise money for iPS research, finishing in 4:03:19. He also ran in the second Osaka Marathon on November 25, 2012.[12]

In 2007, Yamanaka was recognized as a "Person Who Mattered" in the Time Person of the Year edition of Time Magazine.[13] Yamanaka was also nominated as a 2008 Time 100 Finalist.[14] In June 2010, Yamanaka was awarded the Kyoto Prize for reprogramming adult skin cells to pluripotential precursors. Yamanaka developed the method as an alternative to embryonic stem cells, thus circumventing an approach in which embryos would be destroyed.

In May 2010, Yamanaka was given "Doctor of Science honorary degree" by Mount Sinai School of Medicine.[15]

In September 2010, he was awarded the Balzan Prize for his work on biology and stem cells.[16]

Yamanaka has been listed as one of the 15 Asian Scientists To Watch by Asian Scientist magazine on May 15, 2011.[17][18] In June 2011, he was awarded the inaugural McEwen Award for Innovation; he shared the $100,000 prize with Kazutoshi Takahashi(ja), who was the lead author on the paper describing the generation of induced pluripotent stem cells.[19]

In June 2012, he was awarded the Millennium Technology Prize for his work in stem cells.[20] He shared the 1.2 million euro prize with Linus Torvalds, the creator of the Linux kernel.

In October 2012, he and fellow stem cell researcher John Gurdon were awarded the Nobel Prize in Physiology or Medicine "for the discovery that mature cells can be reprogrammed to become pluripotent."[21]

The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka "for the discovery that mature cells can be reprogrammed to become pluripotent."[22]

There are different types of stem cells

. These are some types of cells that will help in understanding the material.

totipotency remains through the first few cell divisions ex. the fertilised egg

The early embryo consists mainly of pluripotent stem cells

ex) blood multipotent cells can develop into various blood cells

Theoretically patient-specific transplantations possible

Much research done Immune rejection reducible via stem cell bank

Pluripotent

Abnormal aging

No immune rejection Safe (clinical trials)

The prevalent view during the early 20th century was that mature cells were permanently locked into the differentiated state and cannot return to a fully immature, pluripotent stem cell state. They thought that cellular differentiation can only be a unidirectional process. Therefore, non-differentiated egg/early embryo cells can only develop into specialized cells. However, stem cells with limited potency (adult stem cells) remain in bone marrow, intestine, skin etc. to act as a source of cell replacement.[23]

The fact that differentiated cell types had specific patterns of proteins suggested irreversible epigenetic modifications or genetic alterations to be the cause of unidirectional cell differentiation. So, cells progressively become more restricted in the differentiation potential and eventually lose pluripotency.[24]

In 1962, John B. Gurdon demonstrated that the nucleus from a differentiated frog intestinal epithelial cell can generate a fully functional tadpole via transplantation to an enucleated egg. Gurdon used somatic cell nuclear transfer (SCNT) as a method to understand reprogramming and how cells change in specialization. He concluded that differentiated somatic cell nuclei had the potential to revert to pluripotency. This was a paradigm shift during the time. It showed that a differentiated cell nucleus has retained the capacity to successfully revert to an undifferentiated state, with the potential to restart development (pluripotent capacity).

However, the question still remained whether an intact differentiated cell could be fully reprogrammed to become pluripotent.

Shinya Yamanaka proved that introduction of a small set of transcription factors into a differentiated cell was sufficient to revert the cell to a pluripotent state. Yamanaka focused on factors that are important for maintaining pluripotency in embryonic stem (ES) cells. Knowing that transcription factors were involved in the maintenance of the pluripotent state, he selected a set of 24 ES cell transcriptional factors as candidates to reinstate pluripotency in somatic cells.

First, he collected the 24 candidate factors. When all 24 genes encoding these transcription factors were introduced into skin fibroblasts, few actually generated colonies that were remarkably similar to ES cells. Secondly, further experiments were conducted with smaller numbers of transcription factors added to identify the key factors, through a very simple and yet sensitive assay system. Lastly, he identified the four key factors. They found that 4 transcriptional factors (Myc, Oct3/4, Sox2 and Klf4) were sufficient to convert mouse embryonic or adult fibroblasts to pluripotent stem cells (capable of producing teratomas in vivo and contributing to chimeric mice).

These pluripotent cells are called iPS (induced pluripotent stem) cells; they appeared with very low frequency.

iPS cells can be selected by inserting the b-geo gene into the Fbx15 locus. The Fbx15 promoter is active in pluripotent stem cells which induce b-geo expression, which in turn gives rise to G418 resistance; this resistance helps us identify the iPS cells in a culture.

Moreover, in 2007, Yamanaka and his colleagues found iPS cells with germ line transmission (via selecting for Oct4 or Nanog gene). Also in 2007, they were the first to produce human iPS cells.

However, there are some difficulties to overcome. The first is the issue of the very low production rate of iPS cells, and the other is the fact that the 4 transcriptional factors are shown to be oncogenic.

Nonetheless, this is a truly fundamental discovery. This was the first time an intact differentiated somatic cell could be reprogrammed to become pluripotent. This opened up a completely new research field.

In July 2014, a scandal regarding the research of Haruko Obokata was connected to Yamanaka. He could not find the lab notes from the period in question [25] and was made to apologise.[26][27]

Since the original discovery by Yamanaka, much further research has been done in this field, and many improvements have been made to the technology. Here we[who?] discuss the improvements made to Yamanaka's research as well as the future prospects of his findings.

1. The delivery mechanism of pluripotency factors has been improved. At first retroviral vectors, that integrate randomly in the genome and cause deregulation of genes that contribute to tumor formation, were used. However, now, non-integrating viruses, stabilised RNAs or proteins, or episomal plasmids (integration-free delivery mechanism) are used.

2. Transcription factors required for inducing pluripotency in different cell types have been identified (e.g. neural stem cells).

3. Small substitutive molecules were identified, that can substitute for the function of the transcription factors.

4. Transdifferentiation experiments were carried out. They tried to change the cell fate without proceeding through a pluripotent state. They were able to systematically identify genes that carry out transdifferentiation using combinations of transcription factors that induce cell fate switches. They found trandifferentiation within germ layer and between germ layers, e.g., exocrine cells to endocrine cells, fibroblast cells to myoblast cells, fibroblast cells to cardiomyocyte cells, fibroblast cells to neurons

5. Cell replacement therapy with iPS cells is a possibility. Stem cells can replace diseased or lost cells in degenerative disorders and they are less prone to immune rejection. However, there is a danger that it may introduce mutations or other genomic abnormalities that render it unsuitable for cell therapy. So, there are still many challenges, but it is a very exciting and promising research area. Further work is required to guarantee safety for patients.

6. Can medically use iPS cells from patients with genetic and other disorders to gain insights into the disease process. - Amyotrophic lateral sclerosis (ALS), Rett syndrome, spinal muscular atrophy (SMA), 1-antitrypsin deficiency, familial hypercholesterolemia and glycogen storage disease type 1A. - For cardiovascular disease, Timothy syndrome, LEOPARD syndrome, type 1 and 2 long QT syndrome - Alzheimers, Spinocerebellar ataxia, Huntingtons etc.

7. iPS cells provide screening platforms for development and validation of therapeutic compounds. For example, kinetin was a novel compound found in iPS cells from familial dysautonomia and beta blockers & ion channel blockers for long QT syndrome were identified with iPS cells.

Yamanaka's research has opened a new door and the world's scientists have set forth on a long journey of exploration, hoping to find our cells true potential.[28]

In 2013, iPS cells were used to generate a human vascularized and functional liver in mice in Japan. Multiple stem cells were used to differentiate the component parts of the liver, which then self-organized into the complex structure. When placed into a mouse host, the liver vessels connected to the hosts vessels and performed normal liver functions, including breaking down of drugs and liver secretions. [29]

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Shinya Yamanaka - Wikipedia

IPS Cell Therapy Comments Off on Shinya Yamanaka – Wikipedia | May 10th, 2017

Induced pluripotent stem cells have revolutionized stem cell science in the decade since their invention. Theyre yielding clues into the nature of diseases such as cancer and Alzheimers, and are also being tapped for therapy.

But creating these IPS cells is lengthy, complicated and tricky, and the facilities equipped to make them cant accommodate all the scientists whod like to get their hands on them.

A UK-led consortium has removed that bottleneck, by producing 711 lines of ready-to-go IPS cells from healthy individuals. These lines are meant to help scientists understand the normal variations between healthy individuals and those involved in disease, as well as to understand normal human biology and development.

The IPS lines are available for research purposes to academic scientists and industry by contacting the Human Induced Pluripotent Stem Cell Initiative (HipSci), at http://www.hipsci.org and the European Bank for induced Pluripotent Stem Cells at https://www.ebisc.org.

The accomplishment was announced in a study published in Nature. It can be found online at j.mp/711ips.

While many other efforts have generated IPS cells to address rare diseases, this study produces them from healthy volunteers to plumb common genetic variation, Fiona Watt, a lead author on the paper and co-principal investigator of HipSci, from King's College London, said in a statement.

"We were able to show similar characteristics of iPS cells from the same person, and revealed that up to 46 per cent of the differences we saw in iPS cells were due to differences between individuals, Watt said in the statement. These data will allow researchers to put disease variations in context with healthy people."

Andrs Bratt-Leal, director of the Parkinson's Cell Therapy Program at The Scripps Research Institute in La Jolla, agreed.

This kind of study is extremely important because it leads to a deeper understanding of the differences between normal genetic variation and genetic changes that could negatively impact cell behavior, said Bratt-Leal, who was not involved in the study.

This data will help scientists using induced pluripotent stem cells to model diseases as well as scientists developing cell therapies, said Bratt-Leal, who works in the lab of stem cell researcher Jeanne Loring.

Because DNA sequencing has become a routine tool in the lab, enormous amounts of data have been produced, he said. Not only have we have observed a high level of genetic diversity between different people, but also a more subtle variation exists among the cells from an individual person. The next step is a better understanding of how this diversity translates to function and behavior of stem cells and mature cells derived from stem cells.

Loring and Bratt-Leal are studying the use of induced pluripotent stem cells to relieve symptoms of Parkinsons disease. They are in the process of translating the research into a therapy, aided with a grant from the California Institute for Regenerative Medicine.

The work was the product of a large-scale collaboration of scientists from various institutions in the United Kingdom, including the European Molecular Biology Laboratory in Cambridge; Wellcome Trust Sanger Institute in Cambridge; the University of Dundee in Dundee; and the University of Cambridge. Also participating was St Vincent's Institute of Medical Research in Victoria, Australia.

bradley.fikes@sduniontribune.com

(619) 293-1020

UPDATES:

1:00 p.m.: This article was updated with additional details.

This article was originally published at 10:00 a.m.

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Hundreds of new stem cell lines ready to help research - The San Diego Union-Tribune

IPS Cell Therapy Comments Off on Hundreds of new stem cell lines ready to help research – The San Diego Union-Tribune | May 10th, 2017

The kidney is made up of about a million tiny units that filter blood, rid the body of undesired waste products while holding back blood cells and valuable proteins, and control the bodys fluid content. Key to each of these units is a structure known the glomerulus, in which podocyte cells wrap themselves tightly around a tuft of capillaries separated only by a thin membrane composed of extracellular matrix, and leave slits between them to build an actual filtration barrier. Podocytes are the target of many congenital or acquired kidney diseases, and they are often harmed by drugs.

To build an in vitro model of the human glomerulus to probe deeper into its function and vulnerabilities to disease and drug toxicities, researchers have been attempting to engineer human stem cells that in theory can give rise to any mature cell type so that they form into functional podocytes. These cell culture efforts, however, so far have failed to produce populations of mature podocytes pure enough as to be useful for modeling glomerular filtration.

A team led by Donald Ingber, Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and Founding Director of Harvards Wyss Institute of Biologically Inspired Engineering, now reports a solution to this challenge in Nature Biomedical Engineering, which enables the differentiation of human induced pluripotent stem (iPS) cells into mature podocytes with more than 90 percent efficiency.

Linking the differentiation process with organ-on-a-chip technology pioneered by his team, the researchers went on to engineer the first in vitro model of the human glomerulus, demonstrating effective and selective filtration of blood proteins and podocyte toxicity induced by a chemotherapy drug in vitro.

Ingber is also theJudah Folkman Professor of Vascular Biologyat Harvard Medical School (HMS) and the Vascular Biology Program at Boston Childrens Hospital.

The development of a functional human kidney glomerulus chip opens up an entirely new experimental path to investigate kidney biology, carry out highly personalized modeling of kidney diseases and drug toxicities, and the stem cell-derived kidney podocytes we developed could even offer a new injectable cell therapy approach for regenerative medicine in patients with life-threatening glomerulopathies in the future, said Ingber.

Ingbers team has engineered multiple organs-on-chips that accurately mimic human tissue and organ-level physiology. These platforms are currently being evaluated by the Food and Drug Administration (FDA) as a tool to more effectively study the effects of potential chemical and biological hazards found in foods, cosmetics or dietary supplementsthan existing culture systems or animal models. In 2013, his team developed an organ-on-a-chip microfluidic culture device that modeled the human kidneys proximal tubule, which is anatomically connected to the glomerulus and salvages ions from urinary fluid.

Now, with the teams newly engineered human kidney glomerulus-on-a-chip, researchers also can get in vitro access to the kidneys core filtration mechanisms that are critical for drug clearance and pharmacokinetics, in addition to studying human podocytes at work.

To generate almost pure populations of human podocytes in cell culture, Samira Musah, the studys first author and HMS Deans Postdoctoral Fellow who is working with Ingber at the Wyss Institute, leveraged pieces of the stem cell biologists arsenal, and merged them with snippets taken from Ingbers past research on how cells in the body respond to adhesive factors and physical forces in their tissue environments.

Our method not only uses soluble factors that guide kidney development in the embryo but, by growing and differentiating stem cells on extracellular matrix components that are also contained in the membrane separating the glomerular blood and urinary systems, we more closely mimic the natural environment in which podocytes are induced and mature, said Musah. We even succeeded in inducing much of this differentiation process within a channel of the microfluidic chip, whereby applying cyclical motions that mimic the rhythmic deformations living glomeruli experience due to pressure pulses generated by each heartbeat, we achieve even greater maturation efficiencies.

The complete microfluidic system closely resembles a living, three-dimensional cross-section of the human glomerular wall. It consists of an optically clear, flexible, polymeric material the size of a computer memory chip in which two closely opposed microchannels are separated by a porous, extracellular matrix-coated membrane that corresponds to the kidneys glomerular basement membrane. In one of the membrane-facing channels, the researchers grow glomerular endothelial cells to mimic the blood microvessel compartment of glomeruli. The iPS cells are cultured on the opposite side of the membrane in the other channel that represents the glomerulus urinary compartment, where they are induced to form a layer of mature podocytes that extend long cellular processes through the pores in the membrane and contact the underlying endothelial cells. In addition, the devices channels are rhythmically stretched and relaxed at a rate of one heart beat per second by applying cyclic suction to hollow chambers placed on either side of the cell-lined microchannels to mimic physiological deformations of the glomerular wall.

This in vitro system allows us to effectively recapitulate the filtration of small substances contained in blood into the urinary compartment while retaining large proteins in the blood compartment just like in our bodies, and we can visualize and monitor the damage inflicted by drugs that cause breakdown of the filtration barrier in the kidney, said Musah.

The study was also co-authored by Wyss Institute Core Faculty member George Church, who also is Professor of Genetics at HMS and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT), and who served as a co-mentor of Musah with Ingber. Other authors include Akiko Mammoto and Tadanori Mammoto, who at the time of the study were Instructors in the Vascular Biology Program and Department of Surgery at Boston Childrens Hospital, as well as Thomas Ferrante, Sauveur Jeanty, Kristen Roberts, Seyoon Chung, Richard Novak, Miles Ingram, Tohid Fatanat-Didar, Sandeep Koshy, and James Weaver.

Funding for the study was provided by the Defense Advanced Research Projects Agency (DARPA). Musah was supported by a HMS Deans Postdoctoral Fellowship, Postdoctoral Enrichment Program Award from the Burroughs Wellcome Fund, UNCF-Merck Postdoctoral Fellowship, and an NIH/NIDDK Nephrology Training Grant.

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Engineering human stem cells to model the kidney's filtration barrier on a chip - Harvard School of Engineering and Applied Sciences

IPS Cell Therapy Comments Off on Engineering human stem cells to model the kidney’s filtration barrier on a chip – Harvard School of Engineering and Applied Sciences | May 10th, 2017

CAMBRIDGE, Mass. and CROMWELL, Conn., May 04, 2017 (GLOBE NEWSWIRE) -- Cellaria, LLC, a scientific innovator that develops revolutionary new patient-specific models for challenging diseases, and Biological Industries USA (BI-USA), a subsidiary of Biological Industries (Israel), today announced a new sales and marketing agreement to promote custom stem cell services. The partnership combines BI-USAs strength in stem cell culture media and manufacturing with Cellarias comprehensive Stem Cell Services program, which includes industry leading RNA reprogramming and custom differentiation services. Together, the companies will offer one of the industrys most innovative and comprehensive stem cell service offerings available to biotechnology companies and academic institutions.

As part of the agreement, Cellaria will distribute BI-USAs stem cell media offering, including its NutriStem hPSC Medium, a cGMP xeno-free media specifically designed for human pluripotent stem cell culture. Cellaria will also incorporate the product into its stem cell services. BI-USA will market Cellaria's customized stem cell services, establishing an integrated, single source solution for iPS cell line derivation, culture maintenance, banking, characterization and differentiation services.

BI is one of the most respected names in life sciences today, said David Deems, chief executive officer at Cellaria. The companys strong market presence and innovative media products will enhance our stem cell and RNA reprogramming service offerings and significantly increase the availability and appeal of our combined offerings.

This is an important partnership for us, added Tanya Potcova, chief executive officer of BI-USA. In combination, our teams bring a wealth of stem cell experience but also share a common goal of creating higher quality, more consistent research outcomes for researchers in the life sciences field. We are pleased to be working with the team at Cellaria to put the best possible tools and support in the hands of our present and future customers.

Please visit Cellaria and BI at the International Society of Stem Cell Research Annual Meeting in Boston, MA June 14-17, 2017 at booth# 407.

About Cellaria Cellaria creates high quality, next generation in vitro disease models that reflect the unique nature of a patients biology. All models begin with tissue from a patient, capturing clinically relevant details that inform model characterization. For cancer, Cellarias cell models exhibit molecular and phenotypic characteristics that are highly concordant to the patient. For RNA-mediated iPS cell line derivation and stem cell services, Cellarias cell models enable interrogation of patient and disease-specific mechanisms of action. Cellarias innovative products and services help lead the research community to more personalized therapeutics, revolutionizing and accelerating the search for a cure. For more information, visitwww.cellariabio.com.

About Biological Industries Biological Industries (BI) is one of the worlds leading and trusted suppliers to the life sciences industry, with over 35 years experience in cell culture media development and cGMP manufacturing. BIs products range from classical cell culture media to supplements and reagents for stem cell research and potential cell therapy applications, to serum-free, xeno-free media. BI is committed to a Culture of Excellence through advanced manufacturing and quality-control systems, regulatory expertise, in-depth market knowledge, and extensive technical customer-support, training, and R&D capabilities.

Biological Industries USA (BI-USA) is the US commercialization arm of BI, with facilities in Cromwell, Connecticut. Members of the BI-USA team share a history and expertise of innovation and success in the development of leading-edge technologies in stem cell research, cellular reprogramming, and regenerative medicine. For more information, visit http://www.bioind.com or connect onLinkedIn,Twitter, andFacebook.

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Cellaria and Biological Industries USA Partner on Stem Cell Media ... - Yahoo Finance

IPS Cell Therapy Comments Off on Cellaria and Biological Industries USA Partner on Stem Cell Media … – Yahoo Finance | May 5th, 2017

Colorado State University is one of multiple research institutions that uses stem cells from aborted fetal tissue to research HIV and AIDS, a practice some say is unnecessary and immoral, but researchers say is essential.

Emily Faulkner, a senior biology major at CSU and founder of the anti-abortion group, CSU Students for Life, has been advocating against the Universitys use of fetal tissue for moral and legal reasons. Faulkner believes the University has illegally obtained fetal tissue for research and still could be after similar allegations against Planned Parenthood and CSU arose in 2015.

Earlier this semester, Faulkner hung posters that said CSU buys trafficked baby parts but says they were ripped down an hour later.

For a community that expresses tolerance for (many other communities) it seems to be very intolerant of the pro-life community, Faulkner said. Its really hard to open peoples minds to actually see whats going on, especially when theres so much intolerance.

In January, a Republican panel from the House of Representatives released a report suggesting some Planned Parenthood clinics and firms sold fetal tissue for profit, which is illegal under federal law. The report concluded over a year-long investigation after similar allegations against Planned Parenthood arose in 2015.

The report cited documents indicating the University paid the tissue procurement organizations StemExpress and Advanced Bioscience Resources $2,000 and $100,000, respectively, for fetal tissue between 2010 and 2015. It is illegal to buy fetal tissue, but federal law does not specify how much can be charged for shipping and handling. The report questions whether or not ABR and StemExpress donated the fetal tissue or sold it for profit.

Faulkner brought up CSUs use of fetal tissue this semester in response to the report. She and CSU Students for Life collected signatures on a petition that asked CSU President Tony Frank to investigate whether or not CSU was involved in illegal obtainment of fetal tissue and to acknowledge its use in research.

In response to the 2015 allegations, Frank wrote to Rep. Doug Lamborn stating that CSU was compliant with all state and federal laws in acquiring fetal tissue. According to Executive Director of Public Affairs and Communications, Mike Hooker, and the Vice President for Research, Alan Rudolph, the University has continued to follow the state and federal laws.

(Part of) my job as an institutional official is making sure that we sustain the highest standards for practice even beyond what the feds recommend, Rudolph said.

In addition to legal concerns, Faulkner also has moral concerns. She said that though abortion may be legal, that does not mean it is right. She expressed concern about fetal tissue and organs being harvested from late-term fetuses with beating hearts.

Its quite inhumane, Faulkner said. Were talking about actual human beings that have livers, brains and hearts. Theyre actually living, breathing beings.

Faulkner said fetal tissue should not be necessary for research on curing or preventing HIV and AIDS, as there is also gene replacement therapy, which takes HIV out of infected cells, and pre-exposure prophylaxis treatment, which consists of taking a pill daily to prevent HIV. Faulkner also said that researchers could use induced pluripotent stem cells (iPS cells) created from adult cells instead of stem cells from fetal tissue.

Pluripotent cells have the ability to become any cell in the body. However, according to Rudolph, iPS stem cells from adults cannot be used in CSUs research on curing and bettering HIV and AIDS, which is conducted by CSU virology professor Ramesh Akkina.

Fetal tissue research, especially the work that Ramesh does, cannot currently be done any other way, Rudolph said.

Akkina uses stem cells from fetal tissue to recreate human immune systems in mice, which Rudolph said are multicellular systems. Akkinas humanized mice can be used to study the effects of countermeasures, including therapeutics, antibodies, vaccines or biologics, on a human immune system meant to improve or cure HIV.

Rudolph said that while scientists are looking into how to conduct research on HIV and AIDS using iPS stem cells, the cells are more limited in their ability to create other types of cells than stem cells from fetal tissue are. He said that cells from fetal tissue are so far back in their development that they have the ability to create complex functions that are lost when cells become older. Cells are more pluripotent.

Faulkner said she hopes that scientists research and work with iPS stem cells.

The lives of those affected by HIV/AIDS are very important, but so are the lives of the unborn, Faulkner wrote in a message to the Collegian. We cannot forget equality for all.

Collegian reporter MQ Borocz can be reached at news@collegian.com or on Twitter @MQBorocz22.

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CSU's use of fetal tissue for HIV/AIDS research sparks controversy - Rocky Mountain Collegian

IPS Cell Therapy Comments Off on CSU’s use of fetal tissue for HIV/AIDS research sparks controversy – Rocky Mountain Collegian | May 5th, 2017

Thursday, May 4, 2017 11:31 AM UTC

CAMBRIDGE, Mass. and CROMWELL, Conn., May 04, 2017 -- Cellaria, LLC, a scientific innovator that develops revolutionary new patient-specific models for challenging diseases, and Biological Industries USA (BI-USA), a subsidiary of Biological Industries (Israel), today announced a new sales and marketing agreement to promote custom stem cell services. The partnership combines BI-USAs strength in stem cell culture media and manufacturing with Cellarias comprehensive Stem Cell Services program, which includes industry leading RNA reprogramming and custom differentiation services. Together, the companies will offer one of the industrys most innovative and comprehensive stem cell service offerings available to biotechnology companies and academic institutions.

As part of the agreement, Cellaria will distribute BI-USAs stem cell media offering, including its NutriStem hPSC Medium, a cGMP xeno-free media specifically designed for human pluripotent stem cell culture. Cellaria will also incorporate the product into its stem cell services. BI-USA will market Cellaria's customized stem cell services, establishing an integrated, single source solution for iPS cell line derivation, culture maintenance, banking, characterization and differentiation services.

BI is one of the most respected names in life sciences today, said David Deems, chief executive officer at Cellaria. The companys strong market presence and innovative media products will enhance our stem cell and RNA reprogramming service offerings and significantly increase the availability and appeal of our combined offerings.

This is an important partnership for us, added Tanya Potcova, chief executive officer of BI-USA. In combination, our teams bring a wealth of stem cell experience but also share a common goal of creating higher quality, more consistent research outcomes for researchers in the life sciences field. We are pleased to be working with the team at Cellaria to put the best possible tools and support in the hands of our present and future customers.

Please visit Cellaria and BI at the International Society of Stem Cell Research Annual Meeting in Boston, MA June 14-17, 2017 at booth# 407.

About Cellaria Cellaria creates high quality, next generation in vitro disease models that reflect the unique nature of a patients biology. All models begin with tissue from a patient, capturing clinically relevant details that inform model characterization. For cancer, Cellarias cell models exhibit molecular and phenotypic characteristics that are highly concordant to the patient. For RNA-mediated iPS cell line derivation and stem cell services, Cellarias cell models enable interrogation of patient and disease-specific mechanisms of action. Cellarias innovative products and services help lead the research community to more personalized therapeutics, revolutionizing and accelerating the search for a cure. For more information, visitwww.cellariabio.com.

About Biological Industries Biological Industries (BI) is one of the worlds leading and trusted suppliers to the life sciences industry, with over 35 years experience in cell culture media development and cGMP manufacturing. BIs products range from classical cell culture media to supplements and reagents for stem cell research and potential cell therapy applications, to serum-free, xeno-free media. BI is committed to a Culture of Excellence through advanced manufacturing and quality-control systems, regulatory expertise, in-depth market knowledge, and extensive technical customer-support, training, and R&D capabilities.

Biological Industries USA (BI-USA) is the US commercialization arm of BI, with facilities in Cromwell, Connecticut. Members of the BI-USA team share a history and expertise of innovation and success in the development of leading-edge technologies in stem cell research, cellular reprogramming, and regenerative medicine. For more information, visit http://www.bioind.com or connect onLinkedIn,Twitter, andFacebook.

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Cellaria and Biological Industries USA Partner on Stem Cell Media and Research - EconoTimes

IPS Cell Therapy Comments Off on Cellaria and Biological Industries USA Partner on Stem Cell Media and Research – EconoTimes | May 4th, 2017

Details WhaTech Channel: Industrial Market Research Published: 04 May 2017 Submitted by John Vardon WhaTech Premium News from QY Research Groups Viewed: 7 times

This report studies the global Regenerative Medicine market, analyzes and researches the Regenerative Medicine development status and forecast in United States, EU, Japan, China, India and Southeast Asia.Learn details of the Size, Status and Forecast 2022

What is Regenerative Medicine?

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History

Applications

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This report focuses on the top players in global market, like

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Table of Contents

Global Regenerative Medicine Market Size, Status and Forecast 2022 1 Industry Overview of Regenerative Medicine 1.1 Regenerative Medicine Market Overview 1.1.1 Regenerative Medicine Product Scope 1.1.2 Market Status and Outlook 1.2 Global Regenerative Medicine Market Size and Analysis by Regions 1.2.1 United States 1.2.2 EU 1.2.3 Japan 1.2.4 China 1.2.5 India 1.2.6 Southeast Asia 1.3 Regenerative Medicine Market by Type 1.3.1 Cell Therapy 1.3.2 Tissue Engineering 1.3.3 Biomaterial 1.3.4 Others 1.4 Regenerative Medicine Market by End Users/Application 1.4.1 Dermatology 1.4.2 Cardiovascular 1.4.3 CNS

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1.4.4 Orthopedic 1.4.5 Others

2 Global Regenerative Medicine Competition Analysis by Players 2.1 Regenerative Medicine Market Size (Value) by Players (2016 and 2017) 2.2 Competitive Status and Trend 2.2.1 Market Concentration Rate 2.2.2 Product/Service Differences 2.2.3 New Entrants 2.2.4 The Technology Trends in Future

3 Company (Top Players) Profiles 3.1 Acelity 3.1.1 Company Profile 3.1.2 Main Business/Business Overview 3.1.3 Products, Services and Solutions 3.1.4 Regenerative Medicine Revenue (Value) (2012-2017) 3.1.5 Recent Developments 3.2 DePuy Synthes 3.2.1 Company Profile 3.2.2 Main Business/Business Overview 3.2.3 Products, Services and Solutions 3.2.4 Regenerative Medicine Revenue (Value) (2012-2017) 3.2.5 Recent Developments 3.3 Medtronic 3.3.1 Company Profile 3.3.2 Main Business/Business Overview

READ MORE atwww.qyresearchgroups.com/report/global-regenerative-medicine-market-size-status-and-forecast-2022

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Latest report on regenerative medicine market just published - WhaTech

IPS Cell Therapy Comments Off on Latest report on regenerative medicine market just published – WhaTech | May 4th, 2017

(EnviroNews World News) Kobe, Japan For more than two million Americans, straight lines may look wavy and the vision in the center of their eye may slowly disappear. Its called age-related macular degeneration (AMD), and there is no cure. But that may change soon.

A surgical team at Kobe City Medical Center General Hospital in Japan recently injected 250,000 retinal pigment epithelial (RPE) cells into the right eye of a man in his 60s. The cells were derived from donor stem cells stored at Kyoto University. It marked the first time that retinal cells derived from a donors skin have been implanted in a patients eye. The skin cells had been reprogrammed into induced pluripotent stem cells (iPS), which can be grown into most cell types in the body.

The procedure is part of a safety study authorized by Japans Ministry of Health that will involve five patients. Each will be followed closely for one year and continue to receive follow-up exams for three additional years. Project leader Dr. Masayo Takahashi at Riken, a research institution that is part of the study, told the Japan Times, A key challenge in this case is to control rejection. We need to carefully continue treatment.

A previous procedure on a different patient in 2014 used stem cells from the individuals own skin. Two years later, the patient reported showing some improvement in eyesight. But the procedure cost $900,000, leading the study team to move forward using donor cells. They expect the costs to come down to less than $200,000.

Among people over 50 in developed countries, AMD is the leading cause of vision loss. According to the National Eye Institute, 14 percent of white Americans age 80 or older will suffer some form of AMD. The condition is almost three times more common among white adults than among people of color. Women of all races comprise 65 percent of AMD cases.

The lack of a cure has led some to try unproven treatments. Three elderly women lost their sight after paying $5,000 each for a stem cell procedure at a private clinic in Florida. Clinic staff used liposuction to remove fat from the womens bellies. They then extracted stem cells from the fat, which were injected into both eyes of each patient in the same procedure, resulting in vision loss in both eyes. Two of the three victims agreed to a lawsuit settlement with the company that owned the clinic.

Stem cell therapy is still at an early stage. As of January 2016, 10 clinical uses have been approved around the world, all using adult stem cells. These include some forms of leukemia and bone marrow disease, Hodgkin and non-Hodgkin lymphoma and some rare inherited disorders including sickle cell anemia. Stem cell transplants are now often used to treat multiple myeloma, which strikes more than 24,000 people a year in the U.S.

Clinical trials to treat type 1 diabetes, Parkinsons disease, stroke, brain tumors and other conditions are being conducted. The first patient in a nationwide clinical study to receive stem cell therapy for heart failure recently underwent the procedure at the University of Wisconsin School of Medicine and Public Health. An experimental treatment at Keck Medical Center of USC last year on a paralyzed patient restored the 21-year-old mans use of his arms and hands. Harvard scientists see stem cell biology as a path to counter aging and extend human lifespans. But the International Society for Stem Cell Research warns that there are many challenges ahead before these treatments are proven safe and effective.

The U.S. Food and Drug Administration (FDA) regulates stem cells to ensure that they are safe and effective for their intended use. But, that doesnt stop some clinics from preying on worried patients. The FDA warns on its website that the hope that patients have for cures not yet available may leave them vulnerable to unscrupulous providers of stem cell treatments that are illegal and potentially harmful.

While there is yet no magic cure for AMD, the Japan study and others may one day lead there. The Harvard Stem Cell Institute (HSCI) in Boston is currently researching retina stem cell transplants. One approach uses gene therapy to generate a molecule that preserves healthy vision. Another involves Muller cells, which give fish the ability to repair an injured retina.

But these therapies are far off. We are at about the halfway mark, but there is still a precipitous path ahead of us, Takahashi said.

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World's 1st Stem Cell Transplant from Donor to Man's Eye Shows Promise of Restoring Sight - EnviroNews (registration) (blog)

IPS Cell Therapy Comments Off on World’s 1st Stem Cell Transplant from Donor to Man’s Eye Shows Promise of Restoring Sight – EnviroNews (registration) (blog) | April 27th, 2017

Organ transplant rejection might eventually be preventable by giving recipients an immune-suppressing vaccine derived from induced pluripotent stem cells, according to a study led by Japanese researchers.

In mice, the treatment allowed permanent acceptance of heart grafts by selectively inhibiting the immune response to the donor graft, said the study, published April 20 in Stem Cell Reports. The work might also be applicable to autoimmune diseases, the study said.

The study can be found at j.mp/ipscden. The co-first authors were Songjie Cai, Jiangang Hou, and Masayuki Fujino. The senior author was Xiao-Kang Li. All are of the National Research Institute for Child Health and Development in Tokyo.

The IPS cells were matured into donor-type regulatory dendritic cells (DCregs) which in turn caused production of tolerance-inducing regulatory T cells, or Tregs, that allow the graft to be treated as self.

While the technology looks good, a UC San Diego stem cell researcher said it faces a number of hurdles that make practical use of it difficult, especially the difficulty in producing the donor-derived regulatory cells in time to be of use in a transplant.

Use of these Tregs and immature DCregs for transplant has been investigated for several years now. In theory, they would provide a better method of preventing rejection than immunosuppressive drugs that knock down immune functioning across the board.

However, activating Tregs must be done precisely, or other T cell types will be activated, increasing the risk of rejection.

The study found that donor-type dendritic cells reliably activated Tregs and not the other types. Peptide antigens from the graft directed naive CD4+ T cells to mature into donor-specific Tregs, providing a selective immune signal to tolerate the graft.

Use of IPS cells for producing these immune regulatory cells is quite novel, said Dan Kaufman, director of cell therapy at UC San Diego, and affiliated with the universitys Sanford Stem Cell Clinical Center.

Obviously, it fits my interest in making immune cells from ES and IPS cells, Kaufman said. The ability to use these cells to suppress transplant rejection seems quite strong. I think the data is all good.

That said, the findings could be strengthened by extending the work from animals to human xenografts, he said. That would demonstrate that human IPS cells can similarly function, although it would be challenging.

Another limitation is the need to use donor-derived cells to induce immune tolerance.

How you would translate that would be unclear to me, Kaufman said.

Are you going to get a heart and then make IPS cells from that donor, which obviously you couldnt do in a reasonable time frame? Could you create a bank of these types of cells that might be suitable for certain patient populations with certain HLA types? Im not sure. I think that gets a little more speculative.

Another speculative possibility is to make the donor-derived IPS cells grow into an organ, and then also create the immune-regulating cells from these IPS cells to selectively induce tolerance.

But were still, I think, a long ways off from having IPS-derived organs, he said.

Autoimmune disease treatment with this technology is worth exploring, Kaufman said. In that case, the IPSCs would be made from the patients themselves.

More than 118,000 Americans are on the waiting list for an organ transplant, according to the Organ Procurement and Transplantation Network.

bradley.fikes@sduniontribune.com

(619) 293-1020

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Stem cell-based treatment prevents transplant rejection, in animal study - The San Diego Union-Tribune

IPS Cell Therapy Comments Off on Stem cell-based treatment prevents transplant rejection, in animal study – The San Diego Union-Tribune | April 23rd, 2017

MADISON, Wis.--(BUSINESS WIRE)--Cellular Dynamics International (CDI), a FUJIFILM company and a leading developer and manufacturer of induced pluripotent stem cells (iPS), today announced it has signed a collaboration agreement with the Harvard Stem Cell Institute (HSCI), a novel network of stem cell scientists that extends from the University to its affiliated hospitals and the biomedical industry. The objective of the new partnership is to increase the availability of iPS cells and services to the HSCI network and the research community at large.

CDI is honored and excited to partner with Harvard Stem Cell Institute, one of the worlds most prestigious research organizations, said Dr. Bruce Novich, Division President-CNBD for FUJIFILM Holdings America Corporation and Executive Vice President and General Manager of Life Science Business Division for CDI. Our goal is to make iPS cells and technology more accessible so that researchers across disciplines and the various institutions of HSCI can better pursue the promise of stem cell science and regenerative medicine.

Under the terms of the agreement, CDI will collaborate with HSCIs iPS Core Facility by providing iPSC technology support to the stem cell community. In addition, CDI will offer critical iPSC technology elements which may accelerate iPSC based science, technology and applications.

About Cellular Dynamics International:

Cellular Dynamics International (CDI), a FUJIFILM company, is a leading developer and supplier of human cells used in drug discovery, toxicity testing, and regenerative medicine applications. Leveraging technology that can be used to create induced pluripotent stem cells (iPSCs) and differentiated tissue-specific cells from any individual, CDI is committed to advancing life science research and transforming the therapeutic development process in order to fundamentally improve human health. The companys inventoried iCell products and donor-specific MyCell Products are available in the quantity, quality, purity, and reproducibility required for drug and cell therapy development. For more information please visitwww.cellulardynamics.com.

About Fujifilm

FUJIFILM Holdings Corporation, Tokyo, Japan brings continuous innovation and leading-edge products to a broad spectrum of industries, including: healthcare, with medical systems, pharmaceuticals and cosmetics; graphic systems; highly functional materials, such as flat panel display materials; optical devices, such as broadcast and cinema lenses; digital imaging; and document products. These are based on a vast portfolio of chemical, mechanical, optical, electronic, software and production technologies. In the year ended March 31, 2016, the company had global revenues of $22.1 billion, at an exchange rate of 112.54 yen to the dollar. Fujifilm is committed to environmental stewardship and good corporate citizenship. For more information, please visit:www.fujifilmholdings.com.

All product and company names herein may be trademarks of their registered owners.

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Cellular Dynamics International Signs Collaboration Agreement with Harvard Stem Cell Institute - Business Wire (press release)

IPS Cell Therapy Comments Off on Cellular Dynamics International Signs Collaboration Agreement with Harvard Stem Cell Institute – Business Wire (press release) | April 20th, 2017

Plasticell, a developer of cell therapies including hematopoietic cell replacement therapies, recently announced it has partnered with Kings College London to progress preclinical trials of its artificial blood platelet product, manufactured from pluripotent stem cells. The work is supported by a MedCity research grant which funds collaboration between leading SMEs and academics from London universities.

Over 10 million units of platelets are transfused worldwide each year in one of the most common procedures in clinical medicine. However, platelets derived from human donors can transmit infections and trigger serious immune reactions that eventually render the therapy ineffective (a condition known as alloimmune refractoriness). In addition, since platelet donations require pathogen testing and cannot be frozen for later use, supply shortages can occur under certain circumstances.

Plasticell has developed robust, cost-effective methods of producing functional platelets from human induced pluripotent stem cells (iPSCs) and has scaled these up to intermediate bioreactor level, allowing manufacture of product for pre-clinical studies. Kings College will contribute world-leading expertise and in vivo models to characterise the dynamics, lifespan, safety and efficacy of transfused platelets.

In addition to providing a more stable and safe supply of universal platelets, the use of iPS cells would allow us to create immunologically compatible matched platelets for patients suffering from alloimmune refractoriness, commented Dr Marina Tarunina, Principal Scientist leading the project at Plasticell.

The project is part of Plasticells hematopoietic cell therapy portfolio, which includes the expansion of umbilical cord- and bone- derived hematopoietic stem cells, and the manufacture of various blood cell types. Plasticell recently announced it had received Innovate UK funding for a 1.1M project to manufacture red blood cells from pluripotent stem cells, in collaboration with the University of Edinburgh.

About Plasticell Plasticell is a biotechnology company leading the use of high throughput technologies to develop stem cell therapies. The Companys therapeutic focus is in hematopoietic stem cell therapy, anaemia and thrombocytopenia, cancer immunotherapy and diabetes/obesity. Plasticells Combinatorial Cell Culture (CombiCult) platform technology, allows it to test very large numbers of cell culture variables in combinations to discover optimal laboratory protocols for the manipulation of stem cells and other cell cultures and has received a number of industry awards including the Queens Award for Enterprise in Innovation and the R&D 100 Award. For more information, visit http://www.plasticell.co.uk.

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Plasticell And Kings College London To Collaborate In Trials Of Blood Platelet Substitute - Clinical Leader

IPS Cell Therapy Comments Off on Plasticell And Kings College London To Collaborate In Trials Of Blood Platelet Substitute – Clinical Leader | April 20th, 2017

MADISON, Wis.--(BUSINESS WIRE)--

Cellular Dynamics International (CDI), a FUJIFILM company and a leading developer and manufacturer of induced pluripotent stem cell-derived products, today announced it has signed a distribution agreement with STEMCELL Technologies, a world leader in iPS cell culture media.

This joint agreement with STEMCELL Technologies will make iPSC technology widely available to researchers worldwide, helping advance biological research leading to cellular therapies and drug discovery, said Dr. Bruce Novich, Division President-CNBD for FUJIFILM Holdings America Corporation and Executive Vice President and General Manager for CDI. We believe that STEMCELL Technologies, a leading developer, manufacturer and seller of stem cell related products, is an ideal partner for CDI, because their global sales and distribution infrastructure delivers to an established and an emerging customer base, which translates into faster access to and deeper penetration of CDIs leading edge technologies and products.

Under the terms of the agreement, STEMCELL Technologies will distribute CDIs iCell catalog of products in North America, Europe, and Singapore, with other countries under consideration. CDIs iCell products are differentiated human induced pluripotent stem cell (iPSC)-derived cells, which include cardiomyocytes, hepatocytes, and others, totaling up to 12 cell types.

STEMCELL Technologies is delighted for the opportunity to bring CDIs innovative products to the global research community. STEMCELL and CDI will work together on progressive solutions for the life science tools market. We look forward to a long and productive partnership with the shared goal of improving human health, said Dr. Allen Eaves, President and CEO of STEMCELL Technologies.

About Cellular Dynamics International:

Cellular Dynamics International (CDI), a FUJIFILM company, is a leading developer and supplier of human cells used in drug discovery, toxicity testing, and regenerative medicine applications. Leveraging technology that can be used to create induced pluripotent stem cells (iPSCs) and differentiated tissue-specific cells from any individual, CDI is committed to advancing life science research and transforming the therapeutic development process in order to fundamentally improve human health. The companys inventoried iCell products and donor-specific MyCell Products are available in the quantity, quality, purity, and reproducibility required for drug and cell therapy development. For more information please visit http://www.cellulardynamics.com.

About Fujifilm

FUJIFILM Holdings Corporation, Tokyo, Japan brings continuous innovation and leading-edge products to a broad spectrum of industries, including: healthcare, with medical systems, pharmaceuticals and cosmetics; graphic systems; highly functional materials, such as flat panel display materials; optical devices, such as broadcast and cinema lenses; digital imaging; and document products. These are based on a vast portfolio of chemical, mechanical, optical, electronic, software and production technologies. In the year ended March 31, 2016, the company had global revenues of $22.1 billion, at an exchange rate of 112.54 yen to the dollar. Fujifilm is committed to environmental stewardship and good corporate citizenship. For more information, please visit: http://www.fujifilmholdings.com.

About STEMCELL Technologies:

As Scientists Helping Scientists, STEMCELL Technologies is committed to providing high-quality cell culture media, cell isolation products, accessory tools and educational services for life science research. Driven by science and a passion for quality, STEMCELL provides over 2500 products to more than 90 countries worldwide. To learn more, visit http://www.stemcell.com.

All product and company names herein may be trademarks of their registered owners.

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Cellular Dynamics International Signs Distribution Deal with STEMCELL Technologies - Yahoo Finance

IPS Cell Therapy Comments Off on Cellular Dynamics International Signs Distribution Deal with STEMCELL Technologies – Yahoo Finance | April 18th, 2017

TERT Identifiers Aliases TERT, CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1, TP2, TRT, hEST2, hTRT, telomerase reverse transcriptase External IDs OMIM: 187270 MGI: 1202709 HomoloGene: 31141 GeneCards: TERT Genetically Related Diseases breast cancer, interstitial lung disease, adenocarcinoma of the lung, prostate cancer, se atraganto con un caramelo, testicular germ cell cancer, idiopathic pulmonary fibrosis, malignant glioma[1] RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) Chr 5: 1.25 1.3 Mb Chr 13: 73.63 73.65 Mb PubMed search [2] [3] Wikidata View/Edit Human View/Edit Mouse

Telomerase reverse transcriptase (abbreviated to TERT, or hTERT in humans) is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex.[4][5]

Telomerases are part of a distinct subgroup of RNA-dependent polymerases. Telomerase lengthens telomeres in DNA strands, thereby allowing senescent cells that would otherwise become postmitotic and undergo apoptosis to exceed the Hayflick limit and become potentially immortal, as is often the case with cancerous cells. To be specific, TERT is responsible for catalyzing the addition of nucleotides in a TTAGGG sequence to the ends of a chromosomes telomeres.[6] This addition of repetitive DNA sequences prevents degradation of the chromosomal ends following multiple rounds of replication.[7]

hTERT absence (usually as a result of a chromosomal mutation) is associated with the disorder Cri du chat.[8][9]

Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component that serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells, resulting in progressive shortening of telomeres. Studies in mice suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity.[10]

The hTERT gene, located on chromosome 5, consists of 16 exons and 15 introns spanning 35 kb. The core promoter of hTERT includes 330 base pairs upstream of the translation start site (AUG since it's RNA by using the words "exons" and "introns"), as well as 37 base pairs of exon 2 of the hTERT gene.[11][12][13] The hTERT promoter is GC-rich and lacks TATA and CAAT boxes but contains many sites for several transcription factors giving indication of a high level of regulation by multiple factors in many cellular contexts.[11] Transcription factors that can activate hTERT include many oncogenes (cancer-causing genes) such as c-Myc, Sp1, HIF-1, AP2, and many more, while many cancer suppressing genes such as p53, WT1, and Menin produce factors that suppress hTERT activity .[13][14] Another form of up-regulation is through demethylation of histones proximal to the promoter region, imitating the low density of trimethylated histones seen in embryonic stem cells.[15] This allows for the recruitment of histone acetyltransferase (HAT) to unwind the sequence allowing for transcription of the gene.[14]

Telomere deficiency is often linked to aging, cancers and the conditions dyskeratosis congenita (DKC) and Cri du chat. Meanwhile, over-expression of hTERT is often associated with cancers and tumor formation.[8][16][17][18] The regulation of hTERT is extremely important to the maintenance of stem and cancer cells and can be used in multiple ways in the field of regenerative medicine.

hTERT is often up-regulated in cells that divide rapidly, including both embryonic stem cells and adult stem cells.[17] It elongates the telomeres of stem cells, which, as a consequence, increases the lifespan of the stem cells by allowing for indefinite division without shortening of telomeres. Therefore, it is responsible for the self-renewal properties of stem cells. Telomerase are found specifically to target shorter telomere over longer telomere, due to various regulatory mechanisms inside the cells that reduce the affinity of telomerase to longer telomeres. This preferential affinity maintains a balance within the cell such that the telomeres are of sufficient length for their function and yet, at the same time, not contribute to aberrant telomere elongation [19]

High expression of hTERT is also often used as a landmark for pluripotency and multipotency state of embryonic and adult stem cells. Over-expression of hTERT was found to immortalize certain cell types as well as impart different interesting properties to different stem cells.[13][20]

hTERT immortalizes various normal cells in culture, thereby endowing the self-renewal properties of stem cells to non-stem cell cultures.[13][21] There are multiple ways in which immortalization of non-stem cells can be achieved, one of which being via the introduction of hTERT into the cells. Differentiated cells often express hTERC and TP1, a telomerase-associated protein that helps form the telomerase assembly, but does not express hTERT. Hence, hTERT acts as the limiting factor for telomerase activity in differentiated cells [13][22] However, with hTERT over-expression, active telomerase can be formed in differentiated cells. This method has been used to immortalize prostate epithelial and stromal-derived cells, which are typically difficult to culture in vitro. hTERT introduction allows in vitro culture of these cells and available for possible future research. hTERT introduction have an advantage over the use of viral protein for immortalization in that it does not involve the inactivation of tumor suppressor gene, which might lead to cancer formation.[21]

Over-expression of hTERT in stem cells changes the properties of the cells.[20][23][24] hTERT over-expression increases the stem cell properties of human mesenchymal stem cells. The expression profile of mesenchymal stem cells converges towards embryonic stem cells, suggesting that these cells may have embryonic stem cell-like properties. However, it has been observed that mesenchymal stem cells undergo decreased levels of spontaneous differentiation.[20] This suggests that the differentiation capacity of adult stem cells may be dependent on telomerase activities. Therefore, over-expression of hTERT, which is akin to increasing telomerase activities, may create adult stem cells with a larger capacity for differentiation and hence, a larger capacity for treatment.

Increasing the telomerase activities in stem cells gives different effects depending on the intrinsic nature of the different types of stem cells.[17] Hence, not all stem cells will have increased stem-cell properties. For example, research has shown that telomerase can be upregulated in CD34+ Umbilical Cord Blood Cells through hTERT over-expression. The survival of these stem cells was enhanced, although there was no increase in the amount of population doubling.[24]

Deregulation of telomerase expression in somatic cells may be involved in oncogenesis.[10]

Genome-wide association studies suggest TERT is a susceptibility gene for development of many cancers,[25] including lung cancer.[26]

Telomerase activity is associated with the number of times a cell can divide playing an important role in the immortality of cell lines, such as cancer cells. The enzyme complex acts through the addition of telomeric repeats to the ends of chromosomal DNA. This generates immortal cancer cells.[27] In fact, there is a strong correlation between telomerase activity and malignant tumors or cancerous cell lines.[28] Not all types of human cancer have increased telomerase activity. 90% of cancers are characterized by increased telomerase activity.[28]Lung cancer is the most well characterized type of cancer associated with telomerase.[29] There is a lack of substantial telomerase activity in some cell types such as primary human fibroblasts, which become senescent after about 3050 population doublings.[28] There is also evidence that telomerase activity is increased in tissues, such as germ cell lines, that are self-renewing. Normal somatic cells, on the other hand, do not have detectable telomerase activity.[30] Since the catalytic component of telomerase is its reverse transcriptase, hTERT, and the RNA component hTERC, hTERT is an important gene to investigate in terms of cancer and tumorigenesis.

The hTERT gene has been examined for mutations and their association with the risk of contracting cancer. Over two hundred combinations of hTERT polymorphisms and cancer development have been found.[29] There were several different types of cancer involved, and the strength of the correlation between the polymorphism and developing cancer varied from weak to strong.[29] The regulation of hTERT has also been researched to determine possible mechanisms of telomerase activation in cancer cells. Glycogen synthase kinase 3 (GSK3) seems to be over-expressed in most cancer cells.[27] GSK3 is involved in promoter activation through controlling a network of transcription factors.[27]Leptin is also involved in increasing mRNA expression of hTERT via signal transducer and activation of transcription 3 (STAT3), proposing a mechanism for increased cancer incidence in obese individuals.[27] There are several other regulatory mechanisms that are altered or aberrant in cancer cells, including the Ras signaling pathway and other transcriptional regulators.[27]Phosphorylation is also a key process of post-transcriptional modification that regulates mRNA expression and cellular localization.[27] Clearly, there are many regulatory mechanisms of activation and repression of hTERT and telomerase activity in the cell, providing methods of immortalization in cancer cells.

If increased telomerase activity is associated with malignancy, then possible cancer treatments could involve inhibiting its catalytic component, hTERT, to reduce the enzymes activity and cause cell death. Since normal somatic cells do not express TERT, telomerase inhibition in cancer cells can cause senescence and apoptosis without affecting normal human cells.[27] It has been found that dominant-negative mutants of hTERT could reduce telomerase activity within the cell.[28] This led to apoptosis and cell death in cells with short telomere lengths, a promising result for cancer treatment.[28] Although cells with long telomeres did not experience apoptosis, they developed mortal characteristics and underwent telomere shortening.[28] Telomerase activity has also been found to be inhibited by phytochemicals such as isoprenoids, genistein, curcumin, etc.[27] These chemicals play a role in inhibiting the mTOR pathway via down-regulation of phosphorylation.[27] The mTOR pathway is very important in regulating protein synthesis and it interacts with telomerase to increase its expression.[27] Several other chemicals have been found to inhibit telomerase activity and are currently being tested as potential clinical treatment options such as nucleoside analogues, retinoic acid derivatives, quinolone antibiotics, and catechin derivatives.[30] There are also other molecular genetic-based methods of inhibiting telomerase, such as antisense therapy and RNA interference.[30]

hTERT peptide fragments have been shown to induce a cytotoxic T-cell reaction against telomerase-positive tumor cells in vitro.[31] The response is mediated by dendritic cells, which can display hTERT-associated antigens on MHC class I and II receptors following adenoviral transduction of an hTERT plasmid into dendritic cells, which mediate T-cell responses.[32] Dendritic cells are then able to present telomerase-associated antigens even with undetectable amounts of telomerase activity, as long as the hTERT plasmid is present.[33]Immunotherapy against telomerase-positive tumor cells is a promising field in cancer research that has been shown to be effective in in vitro and mouse model studies.[34]

Induced pluripotent stem cells (iPS cells) are somatic cells that have been reprogrammed into a stem cell-like state by the introduction of four factors (Oct3/4, Sox2, Klf4, and c-Myc).[35] iPS cells have the ability to self-renew indefinitely and contribute to all three germ layers when implanted into a blastocyst or use in teratoma formation.[35]

Early development of iPS cell lines were not efficient, as they yielded up to 5% of somatic cells successfully reprogrammed into a stem cell-like state.[36] By using immortalized somatic cells (differentiated cells with hTERT upregulated), iPS cell reprogramming was increased by twentyfold compared to reprogramming using mortal cells.[36]

The reactivation of hTERT, and subsequently telomerase, in human iPS cells has been used as an indication of pluripotency and reprogramming to an ES (embryonic stem) cell-like state when using mortal cells.[35] Reprogrammed cells that do not express sufficient hTERT levels enter a quiescent state following a number of replications depending on the length of the telomeres while maintaining stem cell-like abilities to differentiate.[36] Reactivation of TERT activity can be achieved using only three of the four reprogramming factors described by Takahashi and Yamanaka: To be specific, Oct3/4, Sox2 and Klf4 are essential, whereas c-Myc is not.[15] However, this study was done with cells containing endogenous levels of c-Myc that may have been sufficient for reprogramming.

Telomere length in healthy adult cells elongates and acquires epigenetic characteristics similar to those of ES cells when reprogrammed as iPS cells. Some epigenetic characteristics of ES cells include a low density of tri-methylated histones H3K9 and H4K20 at telomeres, as well as an increased detectable amount of TERT transcripts and protein activity.[15] Without the restoration of TERT and associated telomerase proteins, the efficiency of iPS cells would be drastically reduced. iPS cells would also lose the ability to self-renew and would eventually senesce.[15]

DKC (dyskeratosis congenita) patients are all characterized by the defective maintenance of telomeres leading to problems with stem cell regeneration.[16] iPS cells derived from DKC patients with a heterozygous mutation on the TERT gene display a 50% reduction in telomerase activity compared to wild type iPS cells.[37] Conversely, mutations on the TERC gene (RNA portion of telomerase complex) can be overcome by up-regulation due to reprogramming as long as the hTERT gene is intact and functional.[38] Lastly, iPS cells generated with DKC cells with a mutated dyskerin (DKC1) gene cannot assemble the hTERT/RNA complex and thus do not have functional telomerase.[37]

The functionality and efficiency of a reprogrammed iPS cell is determined by the ability of the cell to re-activate the telomerase complex and elongate its telomeres allowing for self-renewal. hTERT is a major limiting component of the telomerase complex and a deficiency of intact hTERT impedes the activity of telomerase, making iPS cells an unsuitable pathway towards therapy for telomere-deficient disorders.[37]

Although the mechanism is not fully understood, exposure of TERT-deficient hematopoietic cells to androgens resulted in an increased level of TERT activity.[39] Cells with a heterozygous TERT mutation, like those in DKC (dyskeratosis congenita) patients, which normally exhibit low baseline levels of TERT, could be restored to normal levels comparable to control cells. TERT mRNA levels are also increased with exposure to androgens.[39] Androgen therapy may become a suitable method for treating circulatory ailments such as bone marrow degeneration and low blood count linked with DKC and other telomerase-deficient conditions.[39]

As organisms age and cells proliferate, telomeres shorten with each round of replication. Cells restricted to a specific lineage are capable of division only a set number of times, set by the length of telomeres, before they senesce.[40] Depletion and uncapping of telomeres has been linked to organ degeneration, failure, and fibrosis due to progenitors' becoming quiescent and unable to differentiate.[19][40] Using an in vivo TERT deficient mouse model, reactivation of the TERT gene in quiescent populations in multiple organs reactivated telomerase and restored the cells abilities to differentiate.[41] Reactivation of TERT down-regulates DNA damage signals associated with cellular mitotic checkpoints allowing for proliferation and elimination of a degenerative phenotype.[41] In another study, introducing the TERT gene into healthy one-year-old mice using an engineered adeno-associated virus led to a 24% increase in lifespan, without any increase in cancer.[42]

The hTERT gene has become a main focus for gene therapy involving cancer due to its expression in tumor cells but not somatic adult cells.[43] One method is to prevent the translation of hTERT mRNA through the introduction of siRNA, which are complimentary sequences that bind to the mRNA preventing processing of the gene post transcription.[44] This method does not completely eliminate telomerase activity, but it does lower telomerase activity and levels of hTERT mRNA seen in the cytoplasm.[44] Higher success rates were seen in vitro when combining the use of antisense hTERT sequences with the introduction of a tumor-suppressing plasmid by adenovirus infection such as PTEN.[45]

Another method that has been studied is manipulating the hTERT promoter to induce apoptosis in tumor cells. Plasmid DNA sequences can be manufactured using the hTERT promoter followed by genes encoding for specific proteins. The protein can be a toxin, an apoptotic factor, or a viral protein. Toxins such as diphtheria toxin interfere with cellular processes and eventually induce apoptosis.[43] Apoptotic death factors like FADD (Fas-Associated protein with Death Domain) can be used to force cells expressing hTERT to undergo apoptosis.[46] Viral proteins like viral thymidine kinase can be used for specific targeting of a drug.[47] By introducing a prodrug only activated by the viral enzyme, specific targeting of cells expressing hTERT can be achieved.[47] By using the hTERT promoter, only cells expressing hTERT will be affected and allows for specific targeting of tumor cells.[43][46][47]

Aside from cancer therapies, the hTERT gene has been used to promote the growth of hair follicles.[48]

A schematic animation for gene therapy is shown as follows.

Telomerase reverse transcriptase has been shown to interact with:

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Telomerase reverse transcriptase - Wikipedia

IPS Cell Therapy Comments Off on Telomerase reverse transcriptase – Wikipedia | April 16th, 2017

Sumitomo Dainippon Pharma Co Ltd has ordered cell culture technologies from Hitachi as part of its effort to develop a treatment for Parkinsons disease.

The order financial terms of which were not provided will see Hitachi supply automated cell culturing technologies designed for the manufacture of induced pluripotent stem cells (iPS).

Dainippon is developing a cell therapy for Parkinsons-related dopamine neuron loss and neurodegeneration in collaboration with both Hitachi and Center for iPS Cell Research and Application, Kyoto University (CiRA).

Part of the project which is funded by the Japanese Agency of Medical Research and Development (AMED) - involves the development of processing methods and technologies for the production of stem cells for regenerative therapies.

The Japanese drug firm has announced several regenerative medicine-based research projects in recent years, beginning in 2015 when it partnered with Sanbio to develop SB623, an allogenic cell therapy for ischemic stroke to improve motor abilities.

Regenerative meds

Regenerative medicine which engineers or replaces damaged cells within human patients has become a popular area of research in Japan sinceShinya Yamanaka won the 2012 Noel Prize for medicine for the discovery that mature cells can be reprogrammed to become pluripotent.

Regenerative medicine is also a big focus for the Japanese Government.

Laws introduced in November 2014 therevised pharmaceutical affairs law and newregenerative medicines legislation mean such products could be reviewed and approved in just two years, if deemed to be effective.

Japans Government further underlined its commitment to regenerative medicine in its budget in January 2015, allocating Y2.5bn ($20.8bn) to the industrialisation of regenerative medicine evaluation fundamental technology development business.

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Sumitomo Dainippon buys cell therapy processing tech from Hitachi - In-PharmaTechnologist.com

IPS Cell Therapy Comments Off on Sumitomo Dainippon buys cell therapy processing tech from Hitachi – In-PharmaTechnologist.com | April 15th, 2017