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The therapeutic promise of human stem cells is indisputably huge, but the process of translating their potential into effective, real-world treatments involves deciphering and resolving a host of daunting complexities.

Writing in the February 25 online issue of the journal PLOS ONE, researchers at University of California, San Diego School of Medicine, with collaborators from The Scripps Research Institute (TSRI), have definitively shown for the first time that the culture conditions in which stem cells are grown and mass-produced can affect their genetic stability.

"Since genetic and epigenetic instability are associated with cancers, we worry that similar alterations in stem cells may affect their safety in therapeutic transplants. Certain mutations might make transplanted stem cells more likely to form tumors, introducing the risk of cancer where it didn't exist before," said co-corresponding author Louise Laurent, MD, PhD, assistant professor and director of perinatal research in the Department of Reproductive Medicine at UC San Diego School of Medicine.

"This study shows the importance of quality control," added Jeanne F. Loring, PhD, professor and director of the Center for Regenerative Medicine at TSRI, and adjunct professor in the UC San Diego Department of Reproductive Medicine and the study's other co-corresponding author. "It's almost certain these cells are safe, but we want to make sure they are free from any abnormalities."

To exploit the transformative powers of human pluripotent stem cells, which include embryonic stem cells and induced pluripotent stem cells, requires producing them in large numbers for transplantation into patients.

"During this culturing process, mutations can occur, and mutations that increase cell survival or proliferation may be favored, such that the cells carrying such mutations could take over the culture," said Laurent.

Human pluripotent stem cells are cultured in several different ways. Key variables are the surfaces upon which the cells are cultured, called the substrate, and the methods used to transfer cells from one culture dish into another as they grow, called the passage method.

Originally, scientists determined that stem cells grew best when cultured atop of a "feeder" layer that included other types of cells, such as irradiated mouse embryonic fibroblasts. For reasons not fully understood, these cells provide stem cells with factors that support their growth. However, concerns about the feeder cells also introducing undesirable materials into stem cells has prompted development of feeder-free cultures.

Moving cells from one culture dish to another has traditionally been done manually, with technicians physically separating the cultured cells into small clumps with an instrument. "It's very labor-intensive," said Laurent, "so new methods that use enzymes to separate individual cells were created."

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Methods to multiply pluripotent cells for potential therapies raise worries about cancer

University of Manchester scientists have used graphene to target and neutralise cancer stem cells while not harming other cells.

This new development opens up the possibility of preventing or treating a broad range of cancers, using a non-toxic material.

Writing in the journal Oncotarget, the team of researchers led by Professor Michael Lisanti and Dr Aravind Vijayaraghavan has shown that graphene oxide, a modified form of graphene, acts as an anti-cancer agent that selectively targets cancer stem cells (CSCs). In combination with existing treatments, this could eventually lead to tumour shrinkage as well as preventing the spread of cancer and its recurrence after treatment. However, more pre-clinical studies and extensive clinical trials will be necessary to move this forward into the clinic to ensure patient benefit.

Professor Lisanti, the Director of the Manchester Centre for Cellular Metabolism within the University's Institute of Cancer Sciences, explained: "Cancer stem cells possess the ability to give rise to many different tumour cell types. They are responsible for the spread of cancer within the body -- known as metastasis- which is responsible for 90% of cancer deaths.

"They also play a crucial role in the recurrence of tumours after treatment. This is because conventional radiation and chemotherapies only kill the 'bulk' cancer cells, but do not generally affect the CSCs."

Dr Vijayaraghavan added: "Graphene oxide is stable in water and has shown potential in biomedical applications. It can readily enter or attach to the surface of cells, making it a candidate for targeted drug delivery. In this work, surprisingly, it's the graphene oxide itself that has been shown to be an effective anti-cancer drug.

"Cancer stem cells differentiate to form a small mass of cells known as a tumour-sphere. We saw that the graphene oxide flakes prevented CSCs from forming these, and instead forced them to differentiate into non-cancer stem-cells.

"Naturally, any new discovery such as this needs to undergo extensive study and trials before emerging as a therapeutic. We hope that these exciting results in laboratory cell cultures can translate into an equally effective real-life option for cancer therapy."

The team prepared a variety of graphene oxide formulations for testing against six different cancer types -- breast, pancreatic, lung, brain, ovarian and prostate. The flakes inhibited the formation of tumour sphere formation in all six types, suggesting that graphene oxide can be effective across all, or at least a large number of different cancers, by blocking processes which take place at the surface of the cells. The researchers suggest that, used in combination with conventional cancer treatments, this may deliver a better overall clinical outcome.

Dr Federica Sotgia, one of the co-authors of the study concluded: "These findings show that graphene oxide could possibly be applied as a lavage or rinse during surgery to clear CSCs or as a drug targeted at CSCs.

More:
Graphene shows potential as novel anti-cancer therapeutic strategy

February 24, 2015

Stop staring into the sun. (Credit: Thinkstock)

Shayne Jacopian for redOrbit.com @ShayneJacopian

Oculus reparo!

The incantation uttered by Hermione Granger on the train to Hogwarts in Harry Potter and the Sorcerers Stone translates to eye repair, but the spell simply fixed Harry Potters broken glasses. The actual key to repairing damaged eyeballs may lie in extracted teeth, according to research from the University of Pittsburgh.

Corneal tissue is normally transplanted from donors, and many times the body rejects the foreign matter. Growing new corneal tissue with a patients own cells could effectively eliminate these problems.

[STORY: Mice stem cells capable of regenerating bone, cartilage]

The scientists extracted dental pulp from human wisdom teeth and used stem cells to engineer corneal stromal cells, or keratocytes. They then injected the human cells into the corneas of mice, where they showed no signs of rejection.

Cells extracted from humans still worked in mice. Science: 1, Magic: 0.

Less focus on donors

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Dental stem cells could repair eyeballs

Those pesky wisdom teeth may be useful after all.

Researchers at the University of Pittsburgh School of Medicine say the dental pulp found in wisdom teeth is rich in stem cells that someday could be used to repair injured corneas.

Wisdom teeth have a pretty powerful population of stem cells, said Fatima Syed-Picard of Pitt's Department of Ophthalmology, lead author of a paper published Monday in the journal STEM CELLS Translational Medicine. It's not just your wisdom teeth; it's all your teeth. You can get similar stem cells from baby teeth.

The findings could lead to a new source of corneal transplant tissue to repair scarring of the cornea, the clear outermost layer of the eye, the researchers said. The scarring, caused by trauma, infections or genetic diseases, can result in permanent vision loss.

The team in the laboratory of ophthalmology professor James Funderburgh used pulp tissue from adult wisdom teeth obtained in routine extractions at Pitt's School of Dental Medicine.

Scientists cultured the extracted cells and turned them into keraocytes, which are cells that can heal the corneas. They then injected the cells into healthy mice to ensure they could work in a normal environment without being rejected, Syed-Picard said.

The method has not been tested in injured animals, and it could be years away from being tested in humans.

I'm confident that this will be easy to translate to humans in the near future, Syed-Picard said.

The Pitt scientists said they are looking at the wisdom teeth stem cells as a potential treatment to prevent corneal blindness, which afflicts millions of people worldwide.

The treatment of last resort is a corneal transplant using tissue from a deceased donor. Using stem cells from the patient's own tissue could help prevent rejection, they said.

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Dental stem cells valuable for cornea repair, University of Pittsburgh researchers find

MIAMI (PRWEB) February 24, 2015

In answer to industry-wide requests for more accessible solutions to stem cell procedures, Global Stem Cells Group, Inc. and Regenestem have announced the launch of two new stem cell harvesting and isolation kits.

The Regenestem BMAC 60 mL concentrating system is a high performing concentrating system for bone marrow aspirate. This kit come complete with a bone marrow filter, a bone marrow aspirating needle and a locking syringe to help maintain suction during the aspirating process. The BMAC 60 kit includes bone marrow concentrate up to 11 times the baseline values, to produce 6-8 mL BMC from a 60 mL sample of bone marrow aspirate.

The Regenestem 60 mL Adipose Derived Stem Cell (ADSC) Kit System includes all the tools and consumables for the extraction of adipose-derived stem cells from 60 mL of lipoaspirated fat. The ADSC kit is currently being used in clinical procedures for lung disease, intra-articular injections for osteoarthritis of the knee and hip, cosmetic surgery and acne scarring, dermal injections, stem cell enriched fat transfer, wounds, chronic ulcers and other chronic conditions. The enzymatic component used to obtain the stromal vascular fraction (SVF) is provided by Adistem.

The Regenestem ADSC Kit System is available in three versions:

Gold, to conduct in-office stem cell procedures with certified GMP components for reliable performance.

Platinum, with all the benefits of the basic (gold) kit plus a sterilized PRP close system with vortex engineering method to minimize platelet loss. One set of individually packed Tulip Gems instruments are added for safe and precise adipose tissue extraction.

Titanium, the perfect state-of-the-art deluxe kit system used by a growing number of regenerative medicine physicians and recognized as the perfect preparation for virtually all clinical applications. Built with Emcyte technology, the Regenestem Titanium kit has been independently reviewed and proven in various critical performance points that make a difference in patient outcomes.

The Titanium kit is currently being used in topical procedures such as intra-articular injection for osteoarthritis of the knee and hip, cosmetic surgery and acne scarring, dermal injection, stem cell enriched fat transfer, wounds chronic ulcers among other chronic conditions.

According to Global Stem Cells Group CEO Benito Novas, the entire Global Stem Cells Group faculty and scientific advisory board worked together to develop the kits.

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Global Stem Cells Group, Inc. Announces Launch of New Stem Cell Harvesting Products

Researchers from Cambridge University and Israels Weizmann Institute of Science are claiming a stem cell research breakthrough that would allow a baby to be created from the skin cells from two adults, no matter their gender. This potentially allows for infertile couples to have their own children without resorting to sperm or egg donors, and may provide the means for same sex couples to produce their own babies.

Previously only successful in experiments on mice, the new research has been conducted on human cells for the first time. In this study, the researchers paired stem cell lines from embryos with the skin of a range of different adults, with the resultant cells compared to aborted fetuses to determine an identical match.

Techniques devised to create same-sex offspring are not new. Some experiments involve the manipulation of fibroblasts in mice resulting in offspring with the genetic traits of multiple male mice, whilst others have used bone marrow stem cells extracted from males to trigger spermatogonia.

However, in this latest research, stem cells and adult human skin have been combined for the first time to create an entire new germ-cell line (that is, cells that will become embryos). Derived from ten different donor sources, the new germ-cell lines were created from 10 different donor sources five embryos and five adults.

Intrinsic to this pairing was the SOX17 gene. A master gene, SOX17 usually works to direct stem cells to be programmed to become whatever organs or body parts are required in other research this techniques has been used to create lung, gut, and pancreas cells.

The manipulation of the gene to be part of a primordial germ cell specification (that is, direct it to create cells that will become an entire human), however, is a new development pioneered by the team and has allowed them to follow this discovery with actually making primordial germ cells in the lab. This stage in a babys development is known as "specification", and once primordial germ cells become specified, they continue to develop inexorably toward precursor sperm or ova cells.

Creating human egg and sperm cells from the skin of two adults of the same gender immediately raises the possibility of same sex couples procreating and offering an alternate pregnancy path for infertile couples. Of course, it also opens the door to a new minefield of ethical and moral implications, but the researchers note that many people may potentially benefit from the technique.

The results of the research were published in the online journal Cell.

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Stem cell breakthrough may allow same gender couples to create babies