Mesenchymal Stem Cells Beyond Regenerative Medicine

Abstract

Mesenchymal stem cells (MSCs) are competent suitors of cellular therapy due to their therapeutic impact on tissue degeneration and immune-based pathologies. Additionally, their homing and immunomodulatory properties can be exploited in cancer malignancies to transport pharmacological entities, produce anti-neoplastic agents, or induce anti-tumor immunity. Herein, we create a portfolio for MSC properties, showcasing their distinct multiple therapeutic utilities and successes/challenges thereof in both animal studies and clinical trials. We further highlight the promising potential of MSCs not only in cancer management but also in instigating tumor-specific immunity - i.e., cancer vaccination. Finally, we reflect on the possible reasons impeding the clinical advancement of MSC-based cancer vaccines to assist in contriving novel methodologies from which a therapeutic milestone might emanate.

Keywords: MSC; antigen; autoimmunity; cancer; regeneration; vaccine.

FIGURE 1

MSCs as anti-cancer vaccines. MSCs can be genetically modified to overexpress cytokines to instigate innate and adaptive immunity, as a means to protect against neoplasms. Genetic modification can be also used to overexpress tumor antigens and instill anti-tumor humoral and cellular immunity. Likewise, dose- and time-dependent exposure to IFN-γ transforms MSCs, albeit transiently, into APCs capable of providing antigen-specific immune protection. This occurs through induction of MHC class I and II expression, followed by tumor antigen processing and MHC-mediated presentation to T-cells. Despite IFN-γ-induced antigen presentation, other observations report that MSCs simultaneously up-regulate PD-L1 and secrete IDO, both of which inhibit T-cells. Henceforth, overcoming the transient and temporary antigen presenting properties of IFN-γ-exposed MSCs is necessary to achieve vigorous stability and abundance of presented neoantigens, thus helping to create a clinically efficient anti-cancer vaccine.