Johns Hopkins researchers have demonstrated that human liver cells derived from adult cells coaxed into an embryonic state can engraft and begin regenerating liver tissue in mice with chronic liver damage.
iPSCs are made from adult cells that have been genetically reprogrammed to revert to an embryonic stem cell-like state, with the ability to transform into different cell types. Human iPSCs can be generated from various tissues, including skin, blood and liver cells.
For the study, Jang and colleagues generated human iPSCs from a variety of adult human cells, including liver cells, fibroblasts (connective tissue cells), bone marrow stem cells and skin cells. They found that though the iPSCs overall were molecularly similar to each other and to embryonic stem cells, they retained a distinct molecular "signature" inherited from the cell of origin.
Next, they chemically induced the iPSCs to differentiate first into immature and then more mature liver cell types. Regardless of their origin, the different iPSC lines all showed the same ability to develop into liver cells.
Using mice with humanlike liver cirrhosis, the researchers then injected the animals with either 2 million human iPSC-derived liver cells or with normal human liver cells. They discovered that the iPSC-derived liver cells engrafted to the mouse liver with an efficiency of eight to 15 percent, a rate similar to the engraftment rate for adult human liver cells at 11 percent.
Researchers also found the engrafted iPSCs worked well. The scientists detected proteins normally secreted by adult human liver cells, including albumin, alpha-1-antitrypsin, transferrin and fibrinogen, in the blood of mice transplanted with human iPSC-derived liver cells.
Additional studies will need to be completed before clinical trials can begin, Jang says. One concern has been the potential for embryonic stem cells or iPSCs to cause tumors, though no tumors formed in any of the transplanted mice during the seven months they were studied (equating to more than 30 years in a human life). The scientists also plan to evaluate the impact of molecular memory that may linger in iPSCs for other type of cellular fate changes.
Source: Johns Hopkins Medicine
The work, published in the May 11 issue of the journal Science Translational Medicine, suggests that liver cells derived from so-called "induced-pluripotent stem cells (iPSCs)" could one day be used as an alternative to liver transplant in patients with serious liver diseases, bypassing long waiting lists for organs and concerns about immune system rejection of donated tissue.
"Our findings provide a foundation for producing functional liver cells for patients who suffer liver diseases and are in need of transplantation," says Yoon-Young Jang, M.D., Ph.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center. "iPSC-derived liver cells not only can be generated in large amounts, but also can be tailored to each patient, preventing immune-rejection problems associated with liver transplants from unmatched donors or embryonic stem cells."
Although the liver can regenerate in the body, end-stage liver failure caused by diseases like cirrhosis and cancers eventually destroy the liver's regenerative ability, Jang says. Currently, the only option for those patients is to receive a liver organ or liver cell transplant, a supply problem given the severe shortage of donor liver tissue for transplantation. In addition, mature liver cells and adult liver stem cells are difficult to isolate or grow in the laboratory, she says. By contrast, iPSCs can be made from a tiny amount of many kinds of tissue; and the embryonic stem-like iPSCs can grow in laboratory cultures indefinitely.
For the study, Jang and colleagues generated human iPSCs from a variety of adult human cells, including liver cells, fibroblasts (connective tissue cells), bone marrow stem cells and skin cells. They found that though the iPSCs overall were molecularly similar to each other and to embryonic stem cells, they retained a distinct molecular "signature" inherited from the cell of origin.
Next, they chemically induced the iPSCs to differentiate first into immature and then more mature liver cell types. Regardless of their origin, the different iPSC lines all showed the same ability to develop into liver cells.
Using mice with humanlike liver cirrhosis, the researchers then injected the animals with either 2 million human iPSC-derived liver cells or with normal human liver cells. They discovered that the iPSC-derived liver cells engrafted to the mouse liver with an efficiency of eight to 15 percent, a rate similar to the engraftment rate for adult human liver cells at 11 percent.
Researchers also found the engrafted iPSCs worked well. The scientists detected proteins normally secreted by adult human liver cells, including albumin, alpha-1-antitrypsin, transferrin and fibrinogen, in the blood of mice transplanted with human iPSC-derived liver cells.
Additional studies will need to be completed before clinical trials can begin, Jang says. One concern has been the potential for embryonic stem cells or iPSCs to cause tumors, though no tumors formed in any of the transplanted mice during the seven months they were studied (equating to more than 30 years in a human life). The scientists also plan to evaluate the impact of molecular memory that may linger in iPSCs for other type of cellular fate changes.
Source: Johns Hopkins Medicine
DDW
11 May 2011
Research presented at Digestive Disease Week® (DDW) shows that patients taking a blood thinner (clopidogrel) after having polyps removed during colonoscopy were at relatively low risk of bleeding...
.
.
Liver disease could be prevented or treated by changing the way in which screening for Hepatitis C is conducted.
According to a group of research projects being presented at Digestive Disease Week, screening for the virus purely on an age basis rather than the current risk-based programme could help catch more incidences earlier on.
Adrian Di Bisceglie, chairman of the department of internal medicine at Saint Louis University, explained: "These studies suggest that innovative detection practices, as well as different methods of screening, can go a very long way in preventing liver-related diseases and can stave off premature death due to liver disease."Hepatitis C is an infectious disease that affects the liver and, once established, it can progress to cirrhosis of the liver and even liver cancer.
One of the problems with the condition is the fact that there are very few, if any, symptoms present after the initial infection, yet the virus will persist in the liver among the majority of those infected.
This makes screening for the initial condition particularly important when looking to prevent or treat liver disease.
Private liver treatment news: 11 May 2011
May News Letter;
Read the hepc.bull -
our online monthly newsletter (.pdf)
In This Issue
That Fully-Loaded “Cure” Word
Affected by Pharmaceutical Shortages?
Hep C & Me: That “Cure” Word
Veteran's colonoscopy suit runs into trouble in court
Veterans suing the federal government after receiving colonoscopies with potentially contaminated equipment have been dealt a setback in federal court.
Todd J. Campbell, chief judge of the U.S. District Court in Nashville, dismissed one of the veterans’ cases in an order Friday. The judge said the lawsuit failed to meet the requirements for the filing of a medical malpractice lawsuit in Tennessee.
FDA urged to certify medicines more quickly
Health activists have urged the Food and Drug Administration to speed up certification of drugs for fighting Aids.
About 100 patients representing a network of Aids, cancer, kidney disease and mental health patients yesterday rallied at the agency asking for clarification from FDA executives.The group said drug approvals by the agency were moving too slowly, which was holding back access to life-saving medicines.
They had checked with the Government Pharmaceutical Organisation (GPO) about three generic regimens, Efavirenz, Tenofovir and GPO-VIR S7, and found essential scientific documents needed for FDA approval had been submitted years ago.
"This is a matter of life and death for thousands of us, particularly children," she said.
Normally, the FDA spends up to 110 days examining documents, shortened to 70 days for fast-track examinations needed as part of the approval process. However, the approval process for GPO-VIR S7 for HIV-positive children had so far taken years, and still there were no results, said Supatra Nakapew, from the Thai NGO Coalition on Aids.
The group asked how many generic drugs were still pending approval, and whether a certain person hired to check documents for approval might have a conflict of interest with drug companies.
FDA secretary-general Pipat Yingseree said the agency could not certify any drug unless essential scientific documents were sent to support the regimen.
In some cases, the documents sent to support the safety of the drugs were insufficient.
But Dr Pipat said he would ask if a retired FDA official who checks documents as part of the certification process really had a conflict of interest as claimed.
Meanwhile, the Thai Network of People Living with HIV/Aids says more action is needed to stop drug companies renewing patents on life-saving drugs on spurious grounds.
It has sought an assurance from the Commerce Ministry that so-called "evergreen" patents on medicines will be banned, says network president Aphiwat Kwangkaew.
He asked Yanyong Phuangrach, the ministry's permanent secretary who is also chairman of the Patent Committee, to ensure that patents are not renewed in perpetuity if the drug companies owning the patent have not added anything new to medicines.
When patents expire, manufacturers can make cheap copies, called generics. Mr Aphiwat said drug manufacturers which seek an extension to their patents often claim to have added some new ingredients or developed the original drug further, which enables them to secure an extension, blocking rival manufacturers from making cheaper versions.
Mr Aphiwat said some multinational pharmaceutical firms adjust only a little of the drug formula and apply for new patent protection for another 20 years, creating obstacles for the development of cheaper medicines
TRENTON — Authorities have charged 22 people with trafficking millions of dollars worth of oxycodone tablets and selling the drugs to customers across the state, U.S. Attorney Paul Fishman announced today. Among those arrested were two doctors -- one from New Jersey and another from New York. What’s That Smell? Another Johnson & Johnson Recall
Nearly a month has passed without a recall from Johnson & Johnson. This may cause recall withdrawal - pun intended - among those closely tracking the plethora of goods the health care giant has yanked over the past year; over-the-counter meds, hip replacement devices, contact lenses, prescription drugs and surgical sutures.
No comments:
Post a Comment