Navigation Links
Stem cell type resists chemotherapy drug
Date:7/2/2014

PROVIDENCE, R.I. [Brown University] A new study shows that adipose-derived human stem cells, which can become vital tissues such as bone, may be highly resistant to the common chemotherapy drug methotrexate (MTX). The preliminary finding from lab testing may prove significant because MTX causes bone tissue damage in many patients.

MTX is used to treat cancers including acute lymphoblastic leukemia, the most common form of childhood cancer. A major side effect of the therapy, however, is a loss of bone mineral density. Other bone building stem cells, such as bone marrow derived stem cells, have not withstood MTX doses well.

"Kids undergo chemotherapy at such an important time when they should be growing, but instead they are introduced to this very harsh environment where bone cells are damaged with these drugs," said Olivia Beane, a Brown University graduate student in the Center for Biomedical Engineering and lead author of the study. "That leads to major long-term side effects including osteoporosis and bone defects. If we found a stem cell that was resistant to the chemotherapeutic agent and could promote bone growth by becoming bone itself, then maybe they wouldn't have these issues."

Stem cell survivors

Originally Beane was doing much more basic research. She was looking for chemicals that could help purify adipose-derived stem cells (ASCs) from mixed cell cultures to encourage their proliferation. Among other things, she she tried chemotherapy drugs, figuring that maybe the ASCs would withstand a drug that other cells could not. The idea that this could help cancer patients did not come until later.

In the study published online in the journal Experimental Cell Research, Beane exposed pure human ASC cultures, "stromal vascular fraction" (SVF) tissue samples (which include several cell types including ASCs), and cultures of human fibroblast cells, to medically relevant concentrations of chemotherapy drugs for 24 hours. Then she measured how those cell populations fared over the next 10 days. She also measured the ability of MTX-exposed ASCs, both alone and in SVF, to proliferate and turn into other tissues.

Beane worked with co-authors fellow center member Eric Darling, the Manning Assistant Professor in the Department of Molecular Pharmacology, Physiology and Biotechnology, and research assistant Vera Fonseca.

They observed that three chemotherapy drugs cytarabine, etoposide, and vincristine decimated all three groups of cells, but in contrast to the fibroblast controls, the ASCs withstood a variety of doses of MTX exceptionally well (they resisted vincristine somewhat, too). MTX had little or no effect on ASC viability, cell division, senescence, or their ability to become bone, fat, or cartilage tissue when induced to do so.

The SVF tissue samples also withstood MTX doses well. That turns out to be significant, Darling said, because that's the kind of tissue that would actually be clinically useful if an ASC-based therapy were ever developed for cancer patients. Hypothetically, fresh SVF could be harvested from the fat of a donor, as it was for the study, and injected into bone tissue, delivering ASCs to the site.

To understand why the ASCs resist MTX, the researchers conducted further tests. MTX shuts down DNA biosynthesis by binding the protein dihydrofolate reductase so that it is unavailable to assist in that essential task. The testing showed that ASCs ramped up dihydrofolate reductase levels upon exposure to the drug, meaning they produced enough to overcome a clinically relevant dose of MTX.

Toward a therapy?

Now that the researchers are aware of ASC's ability to resist MTX, they are eager to see if they can make progress toward delivering a medical benefit for cancer patients. They plan several more experiments.

One is to test ASC survival and performance after 48- and 72-hour exposures to MTX. Another is to begin examining how the cells fare in mouse models of chemotherapy. They also plan to directly compare ASCs and bone marrow-derived stem cells amid various chemotherapies.

Darling said his team hopes it can make a contribution by helping patients heal from chemotherapy, which does what it must, but at a cost.

"The first step is to save a life," he said. "Chemotherapies do a great job of killing cells and killing the cancer, and that's what you want. But then there is a stage after that where you need to do recovery and regeneration."

Further research will reveal whether stem cells can be part of that process.


'/>"/>

Contact: David Orenstein
david_orenstein@brown.edu
401-863-1862
Brown University
Source:Eurekalert  

Related biology news :

1. Team discovers how western corn rootworm resists crop rotation
2. Why sourdough bread resists mold
3. Harmless human virus may be able to boost the effects of chemotherapy
4. Nanobubbles plus chemotherapy equals single-cell cancer targeting
5. New biomarker for common lung cancer predicts responses to chemotherapy
6. Scientists uncover strategy able to dramatically reduce chemotherapys side effects
7. Neutrons help explain why antibiotics prescribed for chemotherapy cause kidney failure
8. New way to kill lymphoma without chemotherapy
9. Changes to DNA on-off switches affect cells ability to repair breaks, respond to chemotherapy
10. Discovery may help prevent chemotherapy-induced anemia
11. An article in Cell reveals a new resistance mechanism to chemotherapy in breast and ovarian cancer
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Stem cell type resists chemotherapy drug
(Date:12/20/2016)... 20, 2016   Valencell , the leading ... STMicroelectronics (NYSE: STM), a global semiconductor leader ... announced today the launch of a new, highly ... that includes ST,s compact SensorTile turnkey ... biometric sensor system. Together, SensorTile and Benchmark deliver ...
(Date:12/15/2016)... Germany , December 15, 2016 ... announced an agreement with NuData Security, an award-winning ... partnership will enable clients to focus on good customer experience, ... protection regulation. ... In order to provide a one-stop fraud prevention suite, ...
(Date:12/15/2016)... , Dec. 14, 2016 "Increase in ... biometrics market" The mobile biometrics market is expected to ... 49.33 billion by 2022, at a CAGR of 29.3% ... factors such as the growing demand for smart devices, ... transactions. "Software component is expected to grow ...
Breaking Biology News(10 mins):
(Date:1/24/2017)... Reha Technology USA Inc. has ... . The need for Robotic technology in the rehab space ... in the surgical space. Project Walk – Boston ... and adding technology to their continuum of care. They now have ... repetitions which has been shown to improve gait with patients. The ...
(Date:1/24/2017)... Jan. 24, 2017  Applied BioMath ( ... modeling to drug research and development, today ... on Biobetters and Next-Generation Biologics: Innovative Strategies ... Wilkins , PhD, Senior Scientist at Applied ... exploration of mechanistic determinants of antibody drug-conjugate ...
(Date:1/24/2017)... , Jan. 24, 2017 Demonstrating its ongoing ... in Lehighton, Pennsylvania has now ... LLC ( www.prairiedogtech.com ). THE OBSERVER is a system ... endoscopes. The system ensures 100% compliance with safety best ... the challenge of preventing the growth and spread of ...
(Date:1/24/2017)... Ohio (PRWEB) , ... January ... ... announced the release of Version 5.0 of its award-winning CERF ELN ... is a 21CFR11 compliant, collaborative, knowledge asset manager used by laboratories, regulated ...
Breaking Biology Technology: