http://myemail.constantcontact.com/A-must-have-for-immune-research.html?soid=1104362209366&aid=xukfWisUKAk.

http://myemail.constantcontact.com/The-only-way-out-is-through–.html?soid=1104362209366&aid=eyjdlDn3L0I.

Forbes nicely summarizes the results of three studies urging caution for autologous stem cell transplantation, as originally reported from the Knoepfler Lab Stem Cell Blog. “The reality is that there are more questions than answers about the safety of stem cell treatments, and each treatment (depending on the institution, the doctor, and the patient) is likely to have a variable and perhaps unpredictable level of safety.”

Can stem cells aid in the development of bone at the site of dental implants? Julio Carrion, of Stony Brook University, is undertaking a study to see if mesemcymal stem cells can correct alveolar ridge deficiencies – a reduction in supportive bone mass caused by tooth extraction and/or bone resorption.

Master switches: Stem cells can differentiate into approximately 200 different somatic cells. What drives their eventual fate could be the key to efficient channeling of stem cells into regenerative replacements. Scientists at the University of Copenhagen believe they have found the answer: Fbxl10, a protein that binds the polycomb protein complex PRC1. Embryonic stem cells do not properly differentiate in the absence of Fbxl10. Levels of the protein may also govern processes involved in cancer development, according to a report in Molecular Cell…But this is hardly the last word on “holy grail” differentiation enablers. Edinburgh researchers have identified a natural trigger, the protein Tcf15, which kick-starts differentiation. Tcf15 marks subsets of pluripotent cells for somatic lineages, but its activity depends on down-regulation its suppressor protein, Id. Full paper.

Neural stem cells: A report in Cell Stem Cell (full text) describes a technique for repairing myelin with iPSCs derived from human skin cells. The University of Rochester’s Steven Goldman transformed the stem cells into immature versions of myelin-producing brain cells. When injected into myelin-deficient mice, the treatment “substantially increased” the animals’ survival…One concern with autologous adult stem cell therapy is that “diseased” or genetically predisposed somatic cells will, after induced pluripotency, recapitulate the disease process. Not true, according to a recent study in Stem Cells Translational Medicine. Maria Teresa González-Garza (Tecnologico de Monterrey, Mexico) has shown that stem cells taken ALS (amyotrophic lateral sclerosis) patients can develop into viable, mature neuron-like cells as do stem cells derived from healthy donors. This work adds credibility for conducting experiments in autologous stem cell transplantation in ALS and other neurodegenerative diseases.

Niche News: Development of a porous, biodegradable niche for bone regeneration, by Ferdous Khan and coworkers at the universities at Edinburgh and Southampton, has European news outlets agog. For example here, and here. The trick was finding a material strong enough to serve as structural bone, and which remained strong as the polymer degraded. The materials that made the cut was a mixture of chitosan, polylactide, and polyvinylacetate with pore structures ranging from 50 to 600 μm – large enough to allow cell colonization, blood vessel growth, and tissue regeneration…Meanwhile Will Shu, at Scotland’s Heriot Watt University has demonstrated a 3D printing technique – normally used to form mechanical prototypes – that creates bubbles of between five and 140 embryonic stem cells floating in culture medium. “The resulting aggregates have controllable and repeatable sizes, and consequently they can be made to order for specific applications,” Shu writes in Biofabrication. The work does not claim the potential for “printed” organs in two years. Rather it shows that 3D printing is gentle enough to maintain stem cell viability and pluripotency, in uniform structures…But from the “watch what you read on the internet” department, a blog reporting this discovery completely, but predictably, gets Shu’s discovery wrong. It relates that 3D printing of embryonic stem cells would “eliminate the need for donors,” as if non-self embryo transplants are not allografts. At the same time, Shu’s technique would “completely eradicate[e] the use of animals for testing.

Business Briefs: James H. Millonig, of the University of Medicine and Dentistry (NJ), has received a five-year, $2.125 million grant from the New Jersey Governor’s Council for Medical Research to develop potential induced pluripotent stem cell (iPSC) treatments for autism spectrum disorder…BioTime has finally closed the deal and acquired Geron’s embryonic stem cell cell business, as reported in Nature Biotechnology. The question, raised by (a not totally disinterested) Wesley Smith at National Review Online is whether anyone still expects anything from this program… RNL BIO (Seol, S. Korea) has filed an Investigational New Drug (IND) application Korean regulators to begin phase 2 clinical trials on the company’s RNL-Astrostem™ stem cell drug in patients with cerebral palsy. RNL-BIO’s phase I trial demonstrated safety, including lack of tumorigenicity.

Israel’s Technion Institute of Technology has established a company to commercialize stem cell technologies developed over the past decade by Professor Joseph Itskovitz-Eldor of Technion’s Bruce and Ruth Rappaport Faculty of Medicine. The firm, Accellta, will market technologies for culturing homogeneous stem cell lines rapidly and cost-effectively.

In response to criticism over potential conflicts of interest from the Institute of Medicine, The California Institute for Regenerative Medicine has endorsed a “framework” to address these concerns. Among the reforms: Board members who compete for CIRM funding would no longer vote on grants. Nature Newsblog article.

Researchers at Sanford-Burnham Medical Research Institute and Johns Hopkins have produced the first “disease in a dish” model for arrythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Huei-Sheng Vincent Chen reports in Nature on his technique, which employs skin cells to create iPSCs from the skin of an ARVD/C patient. When differentiated into heart muscle, the cells recapitulate diseased tissue.

Iqbal Ahmad at the University of Nebraska has devised a novel approach to creating IPSCs. The technique turns adult limbal stem cells from the cornea into cells as powerfully regenerative as embryonic stem cells. This approach could generate retinal progenitor cells that could cure glaucoma and age-related macular degeneration. The work builds off work by John B. Gurdon and Shinya Yamanaka, who won the 2013 Nobel Prize in medicine for their discovery on altering adult stem cells into iPSCs.

Prajina Guha and coworkers at NIH and Boston University have coaxed induced mouse pluripotent stem cells (iPSCs) to become several different cell lines. No adverse immune response was observed upon transplantation into genetically identical mice.  and transplanted those cells into genetically identical mice without triggering a strong immune response. Abstract in Cell Stem Cell.

University at Buffalo research explains how defects in a critical neurological pathway in early development may cause schizophrenia later in life. Writing in Schizophrenia Research¸ Michal Stachowial from Buffalo’s Dept. of Pathology used a mouse model to show how gestational brain changes can cause behavioral problems, similar to the human disease, later in life. The genomic pathway involved, called Integrative Nuclear FGFR 1 Signaling (INFS), is an intersection point for multiple pathways of as many as 160 different genes believed to be involved in Schizophrenia. “We believe this is the first model that explains schizophrenia from genes to development to brain structure and finally to behavior,” Michal says.

Kenji Osafune at Kyoto University has generated kidney tissue from iPSCs, a potential breakthrough for millions who depend on dialysis. Osafune generated part of a urinary tubule, a complex structure that once damaged is difficult to restore. Researchers succeeded in generating intermediate mesoderm tissue, of which kidneys are largely composed, after 11 days of cultivation with a success rate of more than 90%. Paper in Nature Communications.

MIT biologists have identified a gene, lncRNA (dubbed “Braveheart”) that stimulates stem cells to transform into heart cells in the mouse, and that may operate similarly in humans. Learning more about lncRNAs could lead to strategies for drug-based regenerative heart treatments. “It opens a new door to what we could do, and how we could use lncRNAs to induce specific cell types,” says Carla Klattenhoff, a postdoctoral biologist and a lead author of a paper in Cell describing these findings.

HERV-H, a retrovirus that inserted itself into the human genome millions of years ago, may direct how pluripotent stem cells do their magic. Writing in Retrovirology, scientists at U. Mass Medical School believe the discovery could profoundly affect how clinicians use pluripotent stem cells to treat human diseases. “HERV-H is extremely busy in human embryonic stem cells,” said lead researcher Jeremy Luban “[It] is one of the most abundantly expressed genes in pluripotent stem cells and it isn’t found in any other cell types.”

With Japan in perennial recession, the picture for research funding looked bleak as recently as three years ago. Now, the newly elected Liberal Democratic Party-led government is reversing years of budget cuts. Science wins big in the Japanese government’s massive ¥10.3-trillion ($116 billion) economic stimulus package. The biggest beneficiary will be clinical stem cell research, which will receive $235 million. The focus will be in iPSCs.

Leprosy-causing bacteria perform an unlikely “biological alchemy” by infecting specialized nerves, called Schwann cells, and changing them into stem cells. These hijacked stem cells can then change in to any cell type, more effectively spreading the bacteria through the body. “’This is a very sophisticated mechanism,” says Professor Anura Rambukkana of the University of Edinburgh, who led the study which is published in the journal Cell. “It seems the bacterium know the mechanistic interactions of the Schwann cell better than we do.”

“Risk Evaluation Management”

Early Registration Deadline: January 30th, 2013
Registration for Members: $90; Non-Members: $105

Late Registration Deadline: February 4th, 2013
Registration for Members: $105; Non-Members: $120

Event Date: Wednesday, February 6th, 2013
9am-10am Pacific; 12pm-1pm Eastern; 6pm-7pm CET (Europe)
Organized by ISCT Commercialization Committee

Chair: Wouter Van’t Hof, PhD, Senior Director of Regenerative Medicine, Athersys, Inc. USA

Speakers: Natalie Mount, PhD, Chief Clinical Officer, Catapult Limited, UK and Karin Hoogendoorn, PharmD, Associate Director, Janssen Biologics BV, The Netherlands

About the webinar:

Similar to the path for drugs, the development of cell therapy products (CTP) is a high risk and expensive endeavor. Regulatory expectations, development time and specific challenges for each development stage need to be taken into account. The Target Product Profile (TPP) concept provides an important mechanism for risk management and symbolizes the idea of beginning a development process with the ultimate product in mind. More specifically, as stated in regulatory guidance documents, “the TPP should represent the ideal version of what the sponsor would like to claim for product labeling, and the design, conduct, and analysis of clinical trials to maximize efficiency of program development”. Although commonly implemented for drugs, especially in big pharma, it appears the TPP concept has not yet been widely considered as a disciplined planning approach for CTP development.

At its core, a well-utilized TPP is a communication tool that enhances efficient dialogue at various levels in the organization and through stages of development. This begins with internal program management by sponsors from discovery through development. It extends to discussions between sponsor and regulatory agencies and as such can minimize the risk of gaps in data becoming apparent at a late-stage, impacting overall development time and success. Furthermore, it is adaptable as a framework for discussion between academic discoverers, industrial developers/partnerships and investors.

Functionally, the TPP enables advancement of the various development needs in parallel, integrating R&D, (non)clinical, regulatory, process and manufacturing, quality (QA/QC), commercial, labeling, and marketing needs. The document also incorporates flexibility to address the high likelihood for the need for change during product development, e.g. due to technical difficulties, clinical issues around safety and efficacy, changes in competition, IP landscapes and marketing.

In this webinar we will discuss the TPP concept, the structure and utility of the document with specific emphasis on management of the unique risk profile for CTP development and highlight this by case presentation of the use of TPP in the development of an autologous and an allogeneic CTP.

Akron Biotech joined the leader reagent providers to address the needs of the cell therapy industry.

GEN | Magazine Articles: Technologies Evolving for Cellular Therapies.

A free-access article in Nature describes the impact of an early-January U.S. Supreme Court’s decision not to hear a lawsuit to prohibit embryonic stem cell (ESC) research. Surprisingly, the ruling will probably help induced pluripotent stem (iPS) cell work since these cells are gaining quickly on the ESC variety. In just six years, the proportion of posters mentioning iPS cells went from zero to 50%. Read more here.

Inspired by recent research on rodents, the Empire State Stem Cell Board (NYSTEM) has provided a $12.1 million grant to upstate New York medical colleges to “test the safety and effectiveness of implanting stem cells that can reproduce myelin into the central nervous system of MS patients.”

FDA has granted Rockville, MD-based Neuralstem approval to begin a Phase I safety trial of the company’s spinal stem cell therapy, NSI-566, to treat chronic spinal cord injury. The open-label, multi-site study will enroll up to eight patients with complete paralysis below the site of their injury. A late 2012 study published in Cell demonstrated that paralyzed rats transplanted with NSI-566 stem cells recovered significant locomotor function, and the transplanted cells turned into healthy neurons.

Stem cell transplant success in mice holds promise for treating amyotrophic lateral sclerosis (ALS). Results by Stefania Corti at the University of Milan will be presented at the American Academy of Neurology’s 65th Annual Meeting in March. In Corti’s experiment, mice with an animal model of ALS received human neural stem cells derived from iPSCs. The cells migrated to the spinal cord of the mice, matured and multiplied; survival was extended by 20 days and neuromuscular function improved by 15%.

A report in Biological Procedures Online describes a non-invasive, label-free technique for determining the quality of stem cells using laser light scattering. The technique has the potential to screen stem cells rapidly, with an accuracy of 87%.

John VandeBerg and coworkers from the Texas Biomedical Research Institute, San Antonio, have produced a fully functional baboon artery from embryonic stem cells. Researchers replaced normal arterial cells with cells derived from ESCs, then fixed the structure to plastic tubing inside a bioreactor. Three days later, the inner surface began to regenerate; after two weeks, the artery was completely restored. Report in Journal of Cellular and Regenerative Medicine. Press release.

Xiang-Dong Fu at UC San Diego reports on a technique for turning ordinary fibroblasts into functional neurons. The findings, which have implications for treating neurodegenerative diseases like Huntington’s, Parkinson’s and Alzheimer’s, will appear online in advance of the January 17 issue of Cell. The work is based on microRNA miR-124, which modulates levels of PTB, an RNA-binding protein. Cells depleted of PTB become neurons.

In the Jan. 10 issue of Neuron, Harvard’s Albert Edge and coworkers report on regeneration of hair cells inside the ear that resulted in partial recovery of hearing in mouse ears damaged by noise. “Hair cells are the primary receptor cells for sound and are responsible for the sense of hearing,” Edge explained “We show that hair cells can be generated in a damaged cochlea and that hair cell replacement leads to an improvement in hearing.”

Were you able to vote for “Stem Cell Person of the Year,” as we urged you in our previous blog? Paul Knoepfler at U. California, Davis has selected his man: stem cell advocate Roman Reed. Knoepfler selected from 16 finalists suggested by readers of his blog. “Roman made a tremendous difference in 2012 in many ways,” Knoepfler writes, including serving as the catalyst for the TJ Atchison Spinal Cord Injury Research Act in Alabama, which provides $400,000/year in funding for research.

In Brief: Relapsed lymphoma patients treated with rituximab after autologous stem cell transplantation experienced similar outcomes as those in an observation group, according to a study published in the Journal of Clinical Oncology… Zu-yong Wang at the National University of Singapore have demonstrated formation of complex biological systems from stem cells grown in 3D scaffolds… Verastem is collaborating with Laboratory Corporation of America Holdings to validate biomarkers for its lead focal adhesion kinase (FAK) inhibitor VS-6063 in the development of a companion diagnostic. VS-6063 targets cancer stem cells… Phase 2 results using Mesoblast’s allogeneic, or “off-the-shelf”, Mesenchymal Precursor Cells show fusion success comparable to the gold standard bone autograft. Cells were well tolerated, with fusion occurring in 85.7% of high-treatment groups, vs. 75% of patients who received bone autograft.