Stem cell stories that caught our eye: three teams refine cell reprogramming, also stem cell tourism

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Why stem cells in the lab don’t grow up right. A classic cartoon among stem cell fans shows a stem cell telling a daughter cell it can grow up to become anything, and in a living creature that is pretty much true. But in the lab those daughter cells often don’t behave and mature properly. This seems particularly true for stem cells made by reprogramming adult cells through the iPS cell technology.

Tissues, such as heart muscle grown in the lab from stem cells too often look and behave like heart tissue found in a growing embryo rather than like a mature adult. A team at Johns Hopkins decided the best way to solve this problem was to understand the differences between those heart tissues maturing in a lab and those grown naturally and to understand those differences at the molecular level. They looked at which molecular and genetic signaling pathways were turned on in each during development.

After studying 17,000 genes in 200 heart cell samples they found that the pathways in the lab-grown cells were like a map in which the roads don’t line up. Pathways that were supposed to be turned on were not and ones that were supposed to be blocked were open. In a university press release picked up by NewsMedical.net they explain that they now intend to look for ways to correct some of those misguided cellular pathways, in part by making the lab conditions better mimic normal growing conditions.

The result should be tissues grown for research that result in a more accurate model of disease and, potentially, better tissue for transplantation and repair.

Getting the cells needed faster. Pretty much everyone’s cell therapy wish list contains cells that genetically match the patient—to reduce the chance of immune system rejection—and often with the added feature of genetic modification to correct an in-born error. We have the technology to do this. You can use the iPS cell system to reprogram a patient’s adult cells into stem cells and use any number of gene modifying tools to correct the error. But the combined processes can take three months or more; time patients often don’t have.

Researchers at the University of Wisconsin’s Morgridge Institute and the Murdoch Children’s Research Institute in Australia have sped up that process to just two weeks. They found a way to do the stem cell conversion and the genetic correction at the same time and used the trendy new gene-editing tool, CRISPR, which is faster and simpler than other methods. Wisconsin’s stem cell pioneer James Thompson commented on the work led by Sara Howden:

James Thompson

James Thompson

“If you want to conduct therapies using patient-specific iPS cells, the timeline makes it hard to accomplish. If you add correcting a genetic defect, it really looks like a non-starter. You have to make the cell line, characterize it, correct it, then differentiate it to the cells of interest. In this new approach, Dr. Howden succeeded in combining the reprogramming and the gene correction steps together using the new Cas9/CRISPR technology, greatly reducing the time required.”

Howden discussed the work with Australian Broadcasting Corp and her institute issued a press release. In the release she noted than when iPS-based therapies become a reality, the faster method will be critical for certain patients such as children with severe immune deficiency or people with rapidly deteriorating vision.

Skipping the stem cell step. A team at Guangzhou Medical University created unusually pure heart muscle cells directly from skin samples without first turning them into iPS type stem cells. This so-called “direct reprogramming” has been accomplished for a few years, but mostly in nerve tissue and with much less efficiency. This team got 80 percent pure heart muscle.

Heart muscle cells created with traditional iPS cell reprogramming

Heart muscle cells created with traditional iPS cell reprogramming

They also avoided one of the potential problems with iPS technology. Most often, the reprogramming happens using viruses to carry genetic factors into adult cells. The Chinese team used proteins to do the reprogramming, which are much less likely to leave lasting, and potentially cancer-causing, changes in the cells.

“While additional research is needed to fully understand the properties of these cells, the results suggest a potentially safer method to generate cardiac progenitor cells for use as a regenerative therapy after a heart attack,” said Anthony Atala, Editor-in-Chief of STEM CELLS Translational Medicine, which published the work and released a press release picked up by BioSpace.

The research team noted one bit of needed work that reflected back to the first item in this post. They need to see if the new heart cells function like mature native cells and can interact properly with native cells if transplanted.

Stemming stem cell tourism. A pair of medical ethicists, one from Rice University in Houston and one from Wake Forest University in North Carolina, published a call for reforms in how stem cell clinical trials are designed and regulated. They say our system should encourage people to get therapy in the U.S. at regulated clinics rather than go overseas or to seek out unproven therapies here.

“The current landscape of stem cell tourism should prompt a re-evaluation of current approaches to study cell-based interventions with respect to the design, initiation and conduct of U.S. clinical trials,” the authors wrote. “Stakeholders, including scientists, clinicians, regulators and patient advocates, need to work together to find a compromise to keep patients in the U.S. and within the clinical-trial process.”

The web portal MNT wrote an article on the paper based on a Rice press release. The piece notes that many of the same patients who came forward to secure state funding for stem cells like the voter initiative that created CIRM are now tired of waiting for therapies and are seeking out unproven therapies. The authors noted that the problems this causes, in addition to the risks for patients, include the lack of any systematic way to collect data on whether those therapies are really working.

“Policy should be aimed at bringing patients home and fostering responsible scientific research as well as access for patients,” they wrote. “This will require discussions about alternative approaches to the design and conduct of clinical trials as well as to how interventions are approved by the Food and Drug Administration.”

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