Chinese scientists have used genetically modified stem cell therapy to change the history of indiscriminate killing of chemotherapy drugs.

Release date: 2017-07-31

This study co-author: Shirley Zhang (left), Linan Liu (right); collagen fiber network (blue-green) as a cancer cell (red) biophysical properties of biological markers (Source uci.edu)

Recently, scientists at the University of California, Irvine (UCI) published a major study in the internationally renowned journal Science Translational Medicine. Studies have shown that the ability to sense external pressure using mesenchymal stem cells (MSCs) can deliver anticancer drugs to mouse tumors while also reducing the damage of drugs to normal tissues. This is also the first time researchers have genetically engineered mesenchymal stem cells (MSCs) that have the ability to specifically induce hardened tumor tissue to deliver therapeutic drugs to tumor cells.

It is well known that in tissue solid tumors, cancer tissue stiffness is a fairly common phenomenon, but traditional cancer treatment programs do not target this biophysical property. And this is the innovation of this research.

As a senior author of the paper, Dr. Weian Zhao said: "Stiffness is a biomarker that lasts for several years in the body. If Stiffness is used as a therapeutic target, it is difficult for cancer to develop resistance!" : Cancer cells have the ability to sense the stiffness of the surrounding environment, and the ability of cancer cells to move depends on the environment in which they range from hard (bone tissue) to soft (fat tissue). Includes moderately hard tissues such as muscle tissue.)

Based on two recent observations, Zhao Wei'an team discovered the role of biophysical properties in cancer progression, and that stem cells can sense specific sensory sclerotic tumor tissue and can cause cancer cells to make corresponding behavioral changes.

Professor Zhao Wei'an team (image source calit2.uci.edu)

The researchers concluded that the stiffness-sensing characteristics of stem cells can be used to provide targeted delivery of cancer therapeutics. They install promoters in the human MSC genome when the promoter is activated when the cells sense external pressure, just in the cell. Upstream of the gene for pyrimidine deaminase, this enzyme is then released to convert the anticancer drug 5-fluorocytosine to the active form.

Specific induction hardening tumor tissue

During the experiment, the researchers first modified the mesenchymal stem cells isolated from human bone marrow to have the ability to specifically induce hardening of tumor tissue, and then directly injected the stem cells into mice with lung metastatic breast cancer. The next day, mice were injected with 5-fluorocytosine and continued for seven days.

The authors write that mice treated with stem cells continue to express the cytosine deaminase gene compared to the control group. And the researchers found that lung tissue damage in mice treated with stem cells produced an enzyme that was absent in the lungs of other mice, suggesting that stiff-activated cells can accurately target tumors without harming normal tissue. . (Note: This engineered stem cell releases an enzyme after it enters the sclerosing tumor tissue, triggering the conversion of 5-fluorocytosine (prodrug, inactive chemotherapy) into a drug that kills cancer cells, thus avoiding Toxic side effects of healthy tissues)

This study shows that this stem cell therapy has a great inhibitory effect on cancer cell growth in breast cancer lung metastasis mice. At 6 months after treatment, the survival rate of the control mice was about 10%, while the survival rate of mice treated with stem cell therapy was as high as 60%. Even some mice have completely disappeared after treatment.

Designed engineered stem cells infiltrate tumor tissue and activate chemotherapeutic drug activity to kill cancer cells (Source: Science Translational Medicine)

Dr. Zhao Wei'an said that at present, this new treatment is only for metastatic tissues, which makes it possible to avoid the adverse reactions caused by some conventional chemotherapy. In addition, he added: "This study focuses on lung metastases in the lungs, but the technique is also applicable to other metastases, because many solid tumors have the phenomenon of cancerous tissue sclerosis, and this is why our treatment The approach is innovative and powerful because we don't have to spend time identifying and developing a new genetic or protein marker for a variety of cancers."

At present, Zhao Weian's research team has conducted preclinical animal studies, indicating that this treatment is safe. Next, they hope to conduct human clinical trials as soon as possible to verify the effectiveness and safety of the method. Nowadays, they are studying engineered T cells (called CAR-T) with the ability to specifically induce hardening tumor tissue to treat metastatic breast cancer and colon cancer. In addition, they plan to apply this technology to the treatment of diseases such as fibrosis and diabetes that harden the otherwise healthy tissues.

Dr. Zhao Weian has filed a patent application for the technology and plans to commercialize it through the founding company.

Professor Zhao Wei'an (image source calit2.uci.edu)

learning experience

1996-2000 Bachelor degree in Chemistry from Shandong University School of Chemistry

2000-2003 Graduate student of physical chemistry from Shandong University, obtained a master's degree

2004-2008 Ph.D. in Chemistry, McMaster University, Canada

work experience

2004-2008 Assistant Professor, McMaster University, Canada

2008-2011 Postdoctoral Research, Harvard Stem Cell Institute, Harvard Medical School, USA

2011-present Assistant Professor, Stem Cell Research Center, Department of Pharmacology, University of California, Irvine

Main academic and social part-time

Member of the Canadian Chemical Society from 2005 to 2007;

Member of the Materials Research Society since 2006;

Member of the Society of Biomaterial Chemistry since 2010;

Member of the American Chemical Society and member of the International Stem Cell Research Association since 2011.

In 2008, he served as a member of the Executive Board of the 35th Northeastern Biomaterials Conference;

Since 2011, he has been a guest editor of the Nanotechnology, IF 3.6 Biomaterials Nanotechnology chapter.

Since 2012, he has served as a member of the editorial board of Nanotechnology magazine;

Since 2011, he has served as a member of the editorial board of Stem Cell International (founded in 2011);

Since 2012, he has been the guest editor of the Nanoparticle Monitoring Stem Cell Therapy section of Theranostics (founded in 2011);

In 2012, he served as the chairman of the 9th World Biomaterials Conference in Chengdu, China.

Main academic achievements

A total of 32 papers were published, of which the first author or the associated author published 23 papers, and 18 articles affecting SCI factor 3.0 or higher. The publications include Nature Nanotechnology (IF 30.0), Nature Materials (IF 29.9), Agnew. Chem. Int. Ed. (2, IF 12.7), Adv. Mater. (IF 10.8), J. Am. Chem. Soc. (IF 9.0), etc., mainly composed 3 academic book chapters, participated in writing 2 chapters of books, currently He presided over the writing of 1 book, participated in the academic conference report 19 times, and was invited to give lecture reports 20 times.

Source: Medical Maike

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