Despite the remarkable strides of modern medicine, many illnesses remain inevitable death sentences upon diagnosis. Even worse, any hope of survival or prolonged longevity means painful, invasive procedures that only grant a short reprieve from the progression of the disease. This remains the case for a number of brain cancers, including glioblastoma (GBM). In recent years, innovative scientists have been working to develop non-invasive procedures–such as the introduction of engineered stem cells by injection–to help eliminate GBM brain tumors and inhibit the appearance of new tumors for longer periods of time. Current modification and testing with neural stem cells on mice has yielded promising results, suggesting a potential to prolong survival as well as reduce the immediate recurrence of GBM after surgical extractions.

GBM is a fairly common form of brain cancer with up to ten thousand people diagnosed each year. A life expectancy of about twelve to fifteen months is expected after diagnosis. GBM are highly malignant tumors that arise in astrocytes, a cell type that serves as a supportive tissue of the brain, and are consistently nourished by peripheral blood flow. As a result, these tumors are often impossible to treat in any kind of effective manner as they recur in quick succession following surgical removal.

The most promising solution to the dilemma of GBM treatment has been the modification of neural stem cells (NSC) to deliver cytotoxic agents.  These NSCs are engineered to locate GBM tumors, and target the cancer cells for destruction. Using these cytotoxic agents, NSC therapy has showcased a systematic ability to eliminate between seventy and ninety percent of human GBM xenografts introduced into mice and markedly extends the lifespan of the animal. The authors of the study “Tumor-homing cytotoxic human induced neural stems cells for cancer therapy” worked to refine and improve this NSC therapy for use in a clinical setting. Researchers specifically tried to determine the quickest method by which human skin fibroblasts could be converted into tumor-homing NSCs for the sake of immediate patient care. They also measured the general efficacy of the aforementioned tumor-homing NSC with the addition of specific cytotoxic and apoptosis-inducing components, and compared the results of GBM xenograft elimination between agents.

Their subsequent findings only served to reinforce previous data and observations, as well as confirm the viability of their refinements. To obtain NSCs, normal human fibroblasts were transduced with SOX2 in the proper growth medium, a transcription factor found in undifferentiated stem cells for the purpose of maintaining self-renewal.  The necessary number of NSCs were created within a mere four days, which was faster than previous reports and finally feasible in relation to the time frame of clinical GBM patient care. The addition of substances such as CXCR4 antibodies (confirms expression and tumor-homing properties within the h-iNSCTE), TRAIL (inhibits solid GBM growth and prolongs survival), and GCV (amplifies patient survival) in individual succession and as a collective whole produced an improved treatment which they called h-iNSCTE therapy. The acronym h-iNSCTE was created to minimize confusion with previous neural stem cell studies, used only in relation to the work of this particular group. h-NSCs stand for induced neural stem cells, or NSCs created by cell transdifferentiation. The additional TE refers to the iNSC’s early-stage tumor-homing abilities shortly after transdifferentiation, and often includes subsequent engineering with optical reporters and cytotoxic agents. Their human fibroblast-derived NSCs with these modifications both minimized the size of GBM tumors in mice and suppressed the growth of postsurgical GBM, providing promising results for future clinical use.

The possibility and continuous improvement regarding the use of modified neural stem cells for clinical cancer therapy treatment has considerable potential and remains the long term goal of this particular branch of research. The next step would be further research into the isolation and use of NSCs developed from a patient’s own cells instead of transplanting donor cells for GBM therapy. External research suggests that this type of NSC transplant known as autologous transplant lasts longer and elicits a minimal immune response. Although using donors NSCs is most commonly used in preclinical and clinical testing today, its poses the problem of elevated immune rejection as well as reduced efficiency and effectiveness compared to the potential of autologous NSCs. Ultimately, the goal of this research will be the future implementation of these findings in experiments with autologous NSCs to further simplify and enhance the potency of NSC therapy. In addition, their findings were intended to help outline clinical treatments in the near future and may have implications for the treatment of a variety of other cancers such as metastatic, pediatric, and peripheral. h-iNSCTE  therapy currently has the potential to be used as a general anti-cancer therapy; however, further experimentation is necessary to determine and confirm its efficacy with other solid tumor types.


REFERENCES

  1. Bagó, J. R. (2017). Tumor-homing cytotoxic human induced neural stem cells for cancer therapy. Science Translational Medicine AAAS,9(375). doi:10.1126/scitranslmed.aah6510
  2. SOX2 SRY-box 2 [Homo sapiens (human)] – Gene – NCBI. (2017, March 27). Retrieved March 29, 2017, from https://www.ncbi.nlm.nih.gov/gene/6657

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