Mesenchymal Stem Cell Expressing TRAIL as Targeted Therapy against Sensitised Tumour

Abstract

Tapping into the ability of engineered mesenchymal stem cells (MSCs) to mobilise into the tumour has expanded the scope of cancer treatment. Engineered MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) could serve as a platform for an efficient and targeted form of therapy. However, the presence of cancer stem cells (CSCs) that are resistant to TRAIL and apoptosis may represent a challenge for effective treatment. Nonetheless, with the discovery of small molecular inhibitors that could target CSCs and tumour signalling pathways, a higher efficacy of MSC-TRAIL mediated tumour inhibition can be achieved. This might pave the way for a more effective form of combined therapy, which leads to a better treatment outcome. In this review, we first discuss the tumour-homing capacity of MSCs, its effect in tumour tropism, the different approach behind genetically-engineered MSCs, and the efficacy and safety of each agent delivered by these MSCs. Then, we focus on how sensitisation of CSCs and tumours using small molecular inhibitors can increase the effect of these cells to either TRAIL or MSC-TRAIL mediated inhibition. In the conclusion, we address a few questions and safety concerns regarding the utilization of engineered MSCs for future treatment in patients.

M1 Macrophages Promote TRAIL Expression in Adipose Tissue-Derived Stem Cells, Which Suppresses Colitis-Associated Colon Cancer by Increasing Apoptosis of CD133+ Cancer Stem Cells and Decreasing M2 Macrophage Population

“…TRAIL can selectively kill only cancer cells; therefore, studies using TRAIL to treat cancer have been actively conducted [4,5]. Based on the homing characteristic of MSCs into the site of inflammation or tumor, MSCs are used to treat cancers as drug and therapeutic gene carriers [5,21,34,35]. In particular, MSCs engineered with the TRAIL gene have demonstrated therapeutic effects in several tumor models [5,21,35].…”

“…Based on the homing characteristic of MSCs into the site of inflammation or tumor, MSCs are used to treat cancers as drug and therapeutic gene carriers [5,21,34,35]. In particular, MSCs engineered with the TRAIL gene have demonstrated therapeutic effects in several tumor models [5,21,35]. We reported for the first time that ASCs co-cultured with M1 macrophages secreted high levels of TRAIL without gene manipulation.…”

Introductory Chapter: Update on Mesenchymal and Induced Pluripotent Stem Cells

“…In cancer, MSCs are a double-edged sword as they can exert stimulatory effects on tumor development, while they can have inhibitory effects on cancer cell growth and metastases [44]. MSCs have anticancer properties, and they can be engineered or modified to become carriers of suicide genes, employed as carriers of anti-angiogenesis factors, and utilized to target cancer stem cells [45][46][47]. MSCs have recently been engineered to express antiproliferative, antiapoptotic, and antiangiogenic agents that specifically target different types of solid tumors [45].…”

The beneficial effects of varicella zoster virus

“…MSCs have anticancer properties as they can be engineered or modi ied to become carriers of suicide genes that can produce toxic products and subsequently target tumor cells and inhibit tumor expansion while keeping the surrounding healthy tissues intact [272,273]. Additional potential roles of MSCs in cancer therapeutics include: (1) MSCs can be employed as carriers of anti-angiogenesis factors that inhibit tumor growth and prevent metastases, (2) induction of cytokine gene expression in MSCs thus making tumor cells more exposed to the response of the host immune system, (3) antimitotic factors may become a rational target for MSC-based cancer engineering, (4) the use of exosomes as biological delivery vehicles for mRNA transfer as exosomes do not elicit acute immune rejection and do not have risk of tumor formation, and (5) targeting CSCs by engineered MSCs that can express TNF-related apoptosis inducing ligand [272,274].…”

“…The various elements that are implicated in VZV infections are illustrated in igure 3. [101,[204][205][206][207]245,248,268,[272][273][274]276,292,[304][305][306][307][310][311][312][313][320][321][322][323][324]334,341,[343][344][345][346]349,350,361,[368][369][370][371]378,381,387,[397][398][399][400][401][402][403][404]…”