Application of Mesenchymal Stem Cells for Therapeutic Agent Delivery in Anti-tumor Treatment

Abstract

Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells, which can be isolated from different types of tissues including bone marrow, adipose tissue, tooth pulp, and placenta/umbilical cord blood. There isolation from adult tissues circumvents the ethical concerns of working with embryonic or fetal stem cells, whilst still providing cells capable of differentiating into various cell lineages, such as adipocytes, osteocytes and chondrocytes. An important feature of MSCs is the low immunogenicity due to the lack of co-stimulatory molecules expression, meaning there is no need for immunosuppression during allogenic transplantation. The tropism of MSCs to damaged tissues and tumor sites makes them a promising vector for therapeutic agent delivery to tumors and metastatic niches. MSCs can be genetically modified by virus vectors to encode tumor suppressor genes, immunomodulating cytokines and their combinations, other therapeutic approaches include MSCs priming/loading with chemotherapeutic drugs or nanoparticles. MSCs derived membrane microvesicles (MVs), which play an important role in intercellular communication, are also considered as a new therapeutic agent and drug delivery vector. Recruited by the tumor, MSCs can exhibit both pro- and anti-oncogenic properties. In this regard, for the development of new methods for cancer therapy using MSCs, a deeper understanding of the molecular and cellular interactions between MSCs and the tumor microenvironment is necessary. In this review, we discuss MSC and tumor interaction mechanisms and review the new therapeutic strategies using MSCs and MSCs derived MVs for cancer treatment.

Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: Results from the phase 1/2 TREAT‐ME‐1 trial

“…can easily be isolated and expanded in large amounts from adult mammals without major ethical concerns; (b.) undergo targeted tropism towards growing tumors; (c.) migrate deep into the tumor microenvironment; (d.) differentiate into cells of the tumor stroma (cancer‐associated fibroblasts, pericytes and endothelial cells); (e.) have low immunogenicity and can potentially avoid immune rejection …”

“…Several preclinical studies have demonstrated anti‐tumor efficacy using genetically‐engineered MSCs to home transgenes to tumor stroma . In these studies, the modified gene either encoded for a secreted protein that had either a direct or indirect effects on tumor cells, or a ‘suicide’ gene that encoded for an enzyme that converted a prodrug into cytotoxic metabolites; an approach known as gene‐directed enzyme‐producing therapy (GDEPT) …”

Intraoperative Strategies for Minimal Manipulation of Autologous Adipose Tissue for Cell- and Tissue-Based Therapies: Concise Review

“…Cellular SVF has been very effective in the treatment of perianal and recto vaginal fistulas as well as for Crohn's disease , in the treatment for the sequela of radiation injury such as fibrosis, atrophy, retraction, and soft tissue ulceration and to reduce aberrant scar formation . The homing mechanism of cSVF to tumor sites makes them a promising vector for therapeutic delivery to tumors and metastatic niches .…”

Rewiring of endogenous signaling pathways to genomic targets for therapeutic cell reprogramming

“…Current research for enhancing CAR-T cell function is mainly focused on improving synthetic receptors and on conditional expression of immunostimulatory cytokines, such as interleukin 2 (IL-2) and interleukin 12 (IL-12), to combat solid tumors more effectively [3][4][5][6] . Besides immunotherapy, engineered cells have been applied in many other proof-of-concept treatment strategies in animal disease models, including the treatment of metabolic diseases using encapsulated cells 7,8 , and therapeutic agent delivery using transgenic mesenchymal stem cells 9,10 . However, current designs of engineered cells are still limited by the lack of efficient and versatile molecular devices.…”