The potential of regenerative medicine
Alan Russell: The potential of regenerative medicine http://www.youtube.com http://www.ted.com Alan Russell studies regenerative medicine -- a breakthrough way of thinking about disease and injury by helping the body to rebuild itself. He shows how engineered tissue that "speaks the body #39;s language" has helped a man regrow his lost fingertip, how stem cells can rebuild damaged heart muscle, and how cell therapy can regenerate the skin of burned soldiers. This new, low-impact medicine comes just in time, Russell says -- our aging population, with its steeply rising medical bills, will otherwise (and soon) cause a crisis in health care systems around the world. Some graphic medical imagery.From:BroadcastBCViews:1 0ratingsTime:19:30More inScience Technology

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The potential of regenerative medicine - Video

The idea of taking a mature cell and removing its identity (nuclear reprogramming) so that it can then become any kind of cell, holds great promise for repairing damaged tissue or replacing bone marrow after chemotherapy.

Hot on the heels of his recent Nobel prize Dr John B. Gurdon has published in BioMed Central's open access journal Epigenetics and Chromatin research showing that histone H3.3 deposited by the histone-interacting protein HIRA is a key step in reverting nuclei to a pluripotent type, capable of being any one of many cell types.

All of an individual's cells have the same DNA, yet these cells become programmed, as the organism matures, into different types such as heart, or lung or brain.

To achieve this different genes are more or less permanently switched off in each cell lineage. As an embryo grows, after a certain number of divisions, it is no longer possible for cells which have gone down the pathway to become something else.

For example heart cells cannot be converted into lung tissue, and muscle cells cannot form bone.

One way to reprogram DNA is to transfer the nucleus of a mature cell into an unfertilized egg. Proteins and other factors inside the egg alter the DNA switching some genes on and other off until it resembles the DNA of a pluripotent cell. However there seem to be some difficulties with this method in completely wiping the cell's 'memory'.

One of the mechanisms regulating the activation of genes is chromatin and in particular histones. DNA is wrapped around histones and alteration in how the DNA is wound changes which genes are available to the cell.

In order to understand how nuclear reprogramming works Dr Gurdon's team transplanted a mouse nucleus into a frog oocyte (Xenopus laevis). They added fluorescently tagged histones by microinjection, so that they could see where in the cell and nucleus the these histones collected.

Prof Gurdon explained, "Using real-time microscopy it became apparent that from 10 hours onwards H3.3 (the histone involved with active genes) expressed in the oocyte became incorporated into the transplanted nucleus.

When we looked in detail at the gene Oct4, which is known to be involved in making cells pluripotent, we found that H3.3 was incorporated into Oct4, and that this coincided with the onset of transcription from the gene." Prof Gurdon's team also found that Hira, a protein required to incorporate H3.3 into chromatin, was also required for nuclear reprogramming.

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How to make stem cells - nuclear reprogramming moves a step forward

ScienceDaily (Oct. 30, 2012) A team of Duke Medicine researchers has engineered cartilage from induced pluripotent stem cells that were successfully grown and sorted for use in tissue repair and studies into cartilage injury and osteoarthritis. The finding is reported online in the Proceedings of the National Academy of Sciences, and suggests that induced pluripotent stem cells, or iPSCs, may be a viable source of patient-specific articular cartilage tissue.

"This technique of creating induced pluripotent stem cells -- an achievement honored with this year's Nobel Prize in medicine for Shimya Yamanaka of Kyoto University -- is a way to take adult stem cells and convert them so they have the properties of embryonic stem cells," said Farshid Guilak, PhD, Laszlo Ormandy Professor of Orthopaedic Surgery at Duke and senior author of the study.

"Adult stems cells are limited in what they can do, and embryonic stem cells have ethical issues," Guilak said. "What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue -- in this case cartilage, which has no ability to regenerate by itself."

Articular cartilage is the shock absorber tissue in joints that makes it possible to walk, climb stairs, jump and perform daily activities without pain. But ordinary wear-and-tear or an injury can diminish its effectiveness and progress to osteoarthritis. Because articular cartilage has a poor capacity for repair, damage and osteoarthritis are leading causes of impairment in older people and often requires joint replacement.

In their study, the Duke researchers, led by Brian O. Diekman, PhD, a post-doctoral associate in orthopaedic surgery, aimed to apply recent technologies that have made iPSCs a promising alternative to other tissue engineering techniques, which use adult stem cells derived from the bone marrow or fat tissue.

One challenge the researchers sought to overcome was developing a uniformly differentiated population of chondrocytes, cells that produce collagen and maintain cartilage, while culling other types of cells that the powerful iPSCs could form.

To achieve that, the researchers induced chondrocyte differentiation in iPSCs derived from adult mouse fibroblasts by treating cultures with a growth medium. They also tailored the cells to express green fluorescent protein only when the cells successfully became chondrocytes. As the iPSCs differentiated, the chondrocyte cells that glowed with the green fluorescent protein were easily identified and sorted from the undesired cells.

The tailored cells also produced greater amounts of cartilage components, including collagen, and showed the characteristic stiffness of native cartilage, suggesting they would work well repairing cartilage defects in the body.

"This was a multi-step approach, with the initial differentiation, then sorting, and then proceeding to make the tissue," Diekman said. "What this shows is that iPSCs can be used to make high quality cartilage, either for replacement tissue or as a way to study disease and potential treatments."

Diekman and Guilak said the next phase of the research will be to use human iPSCs to test the cartilage-growing technique.

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Researchers engineer cartilage from pluripotent stem cells

Deep within the medulla of the adrenal glands, microscopic chromaffin cells release the two hormones adrenaline and enkephalin to give that rush of energy when we are frightened or that second wind brought on by heavy exercise. According to a study published in STEM CELLS Translational Medicine, a research team in Europe discovered a way to obtain these cells from adult humans and then isolate and force them to become neurons in the lab, bringing researchers one step closer to finding new treatments for neurodegenerative diseases and chronic pain.

Durham, NC (PRWEB) October 29, 2012

Monika Ehrhart-Bornstein, Ph.D., of Dresden University of Technologys Center for Regenerative Therapies (Germany), was a lead investigator on the team. Chromaffin progenitor cells seem to be a promising cell source due to the potential use in autologous transplantations, which avoids the possibility of immune rejection, she explained. Our team had recently described how we isolated chromaffin progenitor cells from the adrenal glands of cows and then treated them so that they differentiated into functional neurons. In this subsequent study, we wanted to learn whether these cells could also be obtained from adult human adrenal glands and then forced to differentiate into neurons, as a prerequisite for future use in transplantation trials.

Dr. Ehrhart-Bornstein collaborated with Dr. Claudia Cavadas, professor at the Center for Neurosciences and Cell Biology, University of Coimbra, Portugal, in leading the team of researchers from both universities on the study. They adapted their bovine study method to obtain and isolate the human cells and then treated them with growth factor. When they examined the cells six days later, they had indeed differentiated into neuron-like cells.

This study both proves the existence of chromaffin progenitor cells in the human adrenal medulla and demonstrates that they can be isolated, Cavadas said. These cells may open new perspectives and challenges in the field of regenerative medicine, especially regarding their potential use in the treatment of neurodegenerative and neuroendocrine diseases.

Dr. Ehrhart-Bornstein added, While protocols need to be established to entirely remove other cell types from progenitor cultures for their therapeutic use, the potential of these progenitor cells to acquire both neuronal and chromaffin cell phenotypes is unquestionable, making them an interesting new cell source for cell-based therapies. The isolation and characterization of these valuable cells from human adrenals is the first step toward their potential future use in transplantation therapies.

These cells are not only an interesting source for cell therapy, said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine, they may contribute to a better understanding of adrenal disease and dysfunction.

###

The full article, Isolation, characterization and differentiation of progenitor cells from human adult adrenal medulla, can be accessed at http://www.stemcellstm.com/content.

About STEM CELLS Translational Medicine: STEM CELLS TRANSLATIONAL MEDICINE (SCTM), published by AlphaMed Press, is a monthly peer-reviewed publication dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

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Stem Cells Behind ‘Adrenaline Rush’ Could Offer Hope for Chronic Pain Sufferers

Public release date: 29-Oct-2012 [ | E-mail | Share ]

Contact: Sarah Avery sarah.avery@duke.edu 919-660-1306 Duke University Medical Center

DURHAM, N.C. A team of Duke Medicine researchers has engineered cartilage from induced pluripotent stem cells that were successfully grown and sorted for use in tissue repair and studies into cartilage injury and osteoarthritis.

The finding is reported online Oct. 29, 2012, in the journal the Proceedings of the National Academy of Sciences, and suggests that induced pluripotent stem cells, or iPSCs, may be a viable source of patient-specific articular cartilage tissue.

"This technique of creating induced pluripotent stem cells an achievement honored with this year's Nobel Prize in medicine for Shimya Yamanaka of Kyoto University - is a way to take adult stem cells and convert them so they have the properties of embryonic stem cells," said Farshid Guilak, PhD, Laszlo Ormandy Professor of Orthopaedic Surgery at Duke and senior author of the study.

"Adult stems cells are limited in what they can do, and embryonic stem cells have ethical issues," Guilak said. "What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue in this case cartilage, which has no ability to regenerate by itself."

Articular cartilage is the shock absorber tissue in joints that makes it possible to walk, climb stairs, jump and perform daily activities without pain. But ordinary wear-and-tear or an injury can diminish its effectiveness and progress to osteoarthritis. Because articular cartilage has a poor capacity for repair, damage and osteoarthritis are leading causes of impairment in older people and often requires joint replacement.

In their study, the Duke researchers, led by Brian O. Diekman, PhD., a post-doctoral associate in orthopaedic surgery, aimed to apply recent technologies that have made iPSCs a promising alternative to other tissue engineering techniques, which use adult stem cells derived from the bone marrow or fat tissue.

One challenge the researchers sought to overcome was developing a uniformly differentiated population of chondrocytes, cells that produce collagen and maintain cartilage, while culling other types of cells that the powerful iPSCs could form.

To achieve that, the researchers induced chondrocyte differentiation in iPSCs derived from adult mouse fibroblasts by treating cultures with a growth medium. They also tailored the cells to express green fluorescent protein only when the cells successfully became chondrocytes. As the iPSCs differentiated, the chondrocyte cells that glowed with the green fluorescent protein were easily identified and sorted from the undesired cells.

Read the rest here:
Duke researchers engineer cartilage from pluripotent stem cells

Washington, October 30 (ANI): Duke Medicine researchers have engineered cartilage from induced pluripotent stem cells that were successfully grown and sorted for use in tissue repair and studies into cartilage injury and osteoarthritis.

The finding suggests that induced pluripotent stem cells, or iPSCs, may be a viable source of patient-specific articular cartilage tissue.

"This technique of creating induced pluripotent stem cells - an achievement honoured with this year's Nobel Prize in medicine for Shimya Yamanaka of Kyoto University - is a way to take adult stem cells and convert them so they have the properties of embryonic stem cells," said Farshid Guilak, PhD, Laszlo Ormandy Professor of Orthopaedic Surgery at Duke and senior author of the study.

"Adult stems cells are limited in what they can do, and embryonic stem cells have ethical issues. What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue - in this case cartilage, which has no ability to regenerate by itself," Guilak noted.

Articular cartilage is the shock absorber tissue in joints that makes it possible to walk, climb stairs, jump and perform daily activities without pain. But ordinary wear-and-tear or an injury can diminish its effectiveness and progress to osteoarthritis.

Because articular cartilage has a poor capacity for repair, damage and osteoarthritis are leading causes of impairment in older people and often requires joint replacement.

In their study, the Duke researchers, led by Brian O. Diekman, PhD., a post-doctoral associate in orthopaedic surgery, aimed to apply recent technologies that have made iPSCs a promising alternative to other tissue engineering techniques, which use adult stem cells derived from the bone marrow or fat tissue.

One challenge the researchers sought to overcome was developing a uniformly differentiated population of chondrocytes, cells that produce collagen and maintain cartilage, while culling other types of cells that the powerful iPSCs could form.

To achieve that, the researchers induced chondrocyte differentiation in iPSCs derived from adult mouse fibroblasts by treating cultures with a growth medium. They also tailored the cells to express green fluorescent protein only when the cells successfully became chondrocytes. As the iPSCs differentiated, the chondrocyte cells that glowed with the green fluorescent protein were easily identified and sorted from the undesired cells.

The tailored cells also produced greater amounts of cartilage components, including collagen, and showed the characteristic stiffness of native cartilage, suggesting they would work well repairing cartilage defects in the body.

Read more:
Cartilage grown in lab dishes using stem cells

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

Verastem, Inc., (VSTM) a clinical-stage biopharmaceutical company focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, announced the presentation of data at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics on November 6-9, 2012, in Dublin, Ireland.

The details of the Verastem poster presentations are as follows:

Title: FAK Inhibitor VS-4718 Attenuates Breast Cancer Stem Cell Function and Inhibits Tumor Growth in Vivo Date: November 8, 2012, from 12:00 to 2:15 pm GMT Session: Signal Transduction Modulators Abstract Number: 400 Location: Auditorium at the Convention Centre Dublin

Title: The Pan-PI3K/mTOR Kinase Inhibitor VS-5584 Preferentially Targets Cancer Stem Cells in Breast Cancer Models Date: November 8, 2012, from 12:00 to 2:15 pm GMT Session: Signal Transduction Modulators Abstract Number: 405 Location: Auditorium at the Convention Centre Dublin

About Verastem, Inc. Verastem, Inc. (VSTM) is a clinical-stage biopharmaceutical company focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells. Cancer stem cells are an underlying cause of tumor recurrence and metastasis. Verastem is developing small molecule inhibitors of signaling pathways that are critical to cancer stem cell survival and proliferation: FAK, PI3K/mTOR and Wnt. For more information, please visit http://www.verastem.com.

Forward-looking statements: Any statements in this press release about future expectations, plans and prospects for the Company constitute forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements. The Company anticipates that subsequent events and developments will cause the Companys views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.

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Verastem to Present at the 2012 Symposium on Molecular Targets and Cancer Therapeutics

Researchers have created adult cartilage from stem cells found in mice. The discovery could lead to new treatments for osteoarthritis and cartilage injury.

The finding is especially important because cartilage does not regenerate itself.

Experts at Duke University created the cartilage from adult cells that have been genetically altered to be structurally similar to embryonic stem cells. The technique of developing those cells, known as induced pluripotent stem cells iIPSCs), was originated by Shimya Yamanaka of Kyoto University. It won this years Nobel Prize for medicine.

The Duke researchers built on that technique to create the cartilage.

What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue, senior author Farshid Guilak said in a news release. iPSCs can be used to make high quality cartilage, either for replacement tissue or as a way to study disease and potential treatment.

Further studies, this time on humans, are needed, he said.

The findings were published in the Proceedings of the National Academy of Sciences.

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Breakthrough: Cartilage Developed from Cells

MONDAY, Oct. 29 (HealthDay News) -- Scientists who created cartilage from adult stem cells in mice say their success could lead to new treatments for cartilage injury and osteoarthritis.

The cartilage was created using induced pluripotent stem cells, which are adult cells that have been genetically altered to have the characteristics of embryonic stem cells. Induced pluripotent stem cells (iPSCs) have the potential to become different types of specialized cells.

"What this research shows in a mouse model is the ability to create an unlimited supply of stem cells that can turn into any type of tissue -- in this case cartilage, which has no ability to regenerate by itself," study senior author Farshid Guilak, a professor of orthopedic surgery at Duke University in Durham, N.C., said in a university news release.

The study was published online Oct. 29 in the journal Proceedings of the National Academy of Sciences.

Study leader Brian Diekman, a post-doctoral associate in orthopedic surgery, said the multi-step process used by the researchers shows "that iPSCs can be used to make high-quality cartilage, either for replacement tissue or as a way to study disease and potential treatments."

Guilak added that the advantage of this technique is "we can grow a continuous supply of cartilage in a dish." He said that in addition to cell-based therapies, this technology can also provide "patient-specific cell and tissue models that could be used to screen for drugs to treat osteoarthritis, which right now does not have a cure or an effective therapy to inhibit cartilage loss."

However, results achieved in animal trials do not necessarily apply to humans. The researchers said they next plan to use human induced pluripotent stem cells to test the cartilage-growing technique.

-- Robert Preidt

Copyright 2012 HealthDay. All rights reserved.

SOURCE: Duke University, news release, Oct. 29, 2012

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Stem Cells to Cartilage? Promising Results Seen in Mice

Public release date: 31-Oct-2012 [ | E-mail | Share ]

Contact: Sarah Collins sarah.collins@enterprise.cam.ac.uk 44-012-237-60335 Cambridge Enteprise University of Cambridge

The potential therapeutic applications of stem cells such as regenerating damaged tissues or organs have generated a great deal of interest over the past decade. While these types of applications are exciting, it is a long journey from lab to clinic. The most immediate impact of stem cells on human health will most likely come from their use in the development of new drugs.

The ability to generate stem cells by reprogramming cells from patients' skin has revolutionised human stem cell research. These cells, known as human induced pluripotent stem cells (hIPSC), can be differentiated into almost any cell type, allowing the opportunity to have a ready source of human cells for testing new therapies. DefiniGEN, a new spin-out company from the University of Cambridge, has been formed to supply hIPSC-derived cells to the drug discovery and regenerative medicine sectors. The company is based on the research of Dr Ludovic Vallier, Dr Tamir Rashid and Professor Roger Pedersen of the Anne McLaren Laboratory of Regenerative Medicine.

Dr Vallier led a team, including Dr Rashid, Dr Nick Hannan and Candy Cho, that developed the technology to generate human liver cells (hepatocytes) in a highly reproducible and scalable manner for commercial use. This represents a major breakthrough in the costly and time-consuming process of developing new therapies. The technology has also been used to effectively model a diverse range of inherited liver diseases and has the potential to accelerate the development of new therapies for these conditions.

The liver is the key organ for metabolising drugs and removing toxins from the body. Consequently, it is often affected by toxic compounds. Demonstrating that a new drug candidate is free from liver toxicity is a key test in the development process, and it is a test that most drug candidates fail.

"If a drug's failure occurs in the clinical phase of development, a great deal of time and money will have been lost," said Dr Vallier. "Therefore, identifying toxic drugs as early as possible is vital to the safety and efficiency of the drug discovery process."

Currently, either primary human hepatocytes or immortalised cell lines are used for toxicity testing. Primary hepatocytes have a high degree of batch-to-batch variation, are expensive and difficult to obtain in suitable quantities, while immortalised cell lines are an inferior model for toxicity testing.

The hIPSC-derived cells produced by DefiniGEN, however, show many of the functional characteristics of primary cells, are highly reproducible and can be made in large quantities, making them ideal for toxicity testing.

In addition, the company's OptiDIFF platform has produced libraries of disease-modelled cells for a range of diseases, including the most common inherited metabolic conditions such as Familial hypercholesterolemia and Alpha 1 anti-trypsin disorder. The cells effectively demonstrate key pathologies of diseases and can be used to improve lead optimisation studies, assisting the development of new therapies for these conditions. The company will also develop pancreatic beta cell products which, in combination with hepatocyte products, will enable the optimised development of new therapeutics for diabetes.

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The role of stem cells in developing new drugs