Modified Skin cells against Brain Cancer
Researchers at the University of North Carolina, working under the leadership of Professor Shawn Hingtgen, have turned skin cells into stem cells that selectively destroy malignant brain tumors known as glioblastomas.
The methodology developed by the authors is based on the latest version of the technology that received the Nobel Prize in 2012, namely, the method of transformation of skin cells – fibroblasts – into induced pluripotent stem cells with the properties of embryonic stem cells. Until now, researchers have been actively exploring the possibilities of using this approach in regenerative medicine and drug screening, and now the authors have proposed a fundamentally new direction of its application – the destruction of brain tumors.
The two-year survival rate of patients with glioblastoma is only 30%, due to the complexity of the treatment of the disease. Even with surgical removal of most of the tumor, it is almost impossible to get rid of metastases that penetrate deep into the brain tissue and inevitably lead to the reappearance of the tumor. Most patients with this disease die within 1.5 years after diagnosis.
The authors hope to improve this statistic with a new personalized glioblastoma treatment method using the patient's own modified skin cells.
As part of their work, they reprogrammed fibroblasts into induced neural stem cells. Experiments on mice have demonstrated the inherent ability of such cells to move through brain tissue and destroy malignant cells that get in the way by triggering the mechanism of their self-destruction, or apoptosis. The authors also developed a method of modifying these cells to ensure their ability to produce a protein that kills tumor cells, which further increased the effectiveness of the approach.
Under the influence of three reprogramming factors, fibroblasts differentiate into induced neural stem cells (iNSCs). Cells containing fluorescent protein make it possible to monitor their migration; "therapeutic" cells contain a protein that provokes apoptosis of malignant cells. Diagram from an article in Nature Communications
Depending on the type of tumor, the experimental approach increased the survival rate of mice by 2.6-3.2 times (by 160-220%). The next stage of the researchers' work will be to reproduce the results using human stem cells, as well as to increase the effectiveness of experimental therapy by modifying such cells, thanks to which they will be able to produce more powerful antitumor compounds.
In addition, the authors are currently engaged in improving the method by increasing the ability of therapeutic cells to remain inside the postoperative cavity. They found that stem cells need a physical matrix to support their vital functions, without which they quickly disperse into tissues and lose their effectiveness. Fibrin glue, widely used in surgical practice, turned out to be a promising candidate for the role of a material for such a matrix. The use of fibrin glue tripled the duration of the preservation period of modified stem cells in the surgical cavity, which further increased the effectiveness of the approach proposed by the authors.
Article by Juli R. Vado et al. Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma published in the journal Nature Communications.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of North Carolina at Chapel Hill: UNC-Chapel Hill researchers make groundbreaking discovery, use skin cells to kill cancer.
29.02.2015