College

The Graduate School

Program

Biomedical Sciences

Publication Date

4-2021

DOI

10.25883/5vj7-sj33

Abstract

Cancers are aggressive, evasive, and ruthless killers, claiming millions of lives every year. Cancers are heterogeneous and there is often no single, clearly defined problem as they harness and manipulate a multitude of fundamental mechanisms at the very essence of life. To investigate these mechanisms and vet potential interventive therapies, humanized mice offer a unique model as a prelude to the use of nanosecond pulse stimulation (NPS), a pulse power technology applying nanosecond duration, high electric field pulses, to ablate human tumors. Immunodeficient mouse strains, NSG and NSG-SGM3, were engrafted with human immune cells and human tumors, which would allow us to study the effects of NPS therapy on the human tumor and the human immune system, albeit not without trials and tribulations. Here we show that mice engrafted with human cord blood CD34+ hematopoietic stem cells (hCD34+ HSC) lack consistency in expansion and chimerism, or variety of immune cell types. Unfortunately, mice that developed the human immune system rejected the human tumors without treatment, while mice that rejected the immune system developed the human tumors. Therefore, we had mice with human immune systems and no tumor to treat, and mice with tumors to treat yet no immune system to study. In non-humanized mice, NPS induced complete tumor death in the patient derived mammary cancer xenograft (PDX) model, but not in the MDA-MB-231 VIM-RFP mammary cancer cell-derived xenograft (CDX) model. The absence of NPS elimination of the CDX is the only known NPS cancer failure and requires further study.

Disciplines

Animal Experimentation and Research | Biomedical Engineering and Bioengineering | Cell Biology | Oncology

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Trials and Tribulations of Humanizing Mice for Cancer Research


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