The Potential of Mesenchymal Stromal Cells in Neuroblastoma Therapy for Delivery of Anti-Cancer Agents and Hematopoietic Recovery

Abstract

Neuroblastoma is one of the most common pediatric cancers and a major cause of cancer-related death in infancy. Conventional therapies including high-dose chemotherapy, stem cell transplantation, and immunotherapy approach a limit in the treatment of high-risk neuroblastoma and prevention of relapse. In the last two decades, research unraveled a potential use of mesenchymal stromal cells in tumor therapy, as tumor-selective delivery vehicles for therapeutic compounds and oncolytic viruses and by means of supporting hematopoietic stem cell transplantation. Based on pre-clinical and clinical advances in neuroblastoma and other malignancies, we assess both the strong potential and the associated risks of using mesenchymal stromal cells in the therapy for neuroblastoma. Furthermore, we examine feasibility and safety aspects and discuss future directions for harnessing the advantageous properties of mesenchymal stromal cells for the advancement of therapy success.

Construction of tandem diabody (IL-6/CD20)-secreting human umbilical cord mesenchymal stem cells and its experimental treatment on diffuse large B cell lymphoma

“…The result was in accordance with other studies that reported the highest level at 6–9 days ranging from 1500 to 8247 pg/ml and could constantly increase for 15 to 30 days after transduction [ 23 , 25 ]. Previous evidence has indicated that the modified MSCs could serve as an excellent local agent delivery vehicle for its innate homing ability [ 35 – 37 ]. The modified MSCs in conjunction with targeted drugs have been introduced in clinical practice: engineered UCMSCs produced TRAIL for intracranial glioma [ 38 ], and MSCs loaded with oncolytic reovirus ReoT3D for colorectal cancer [ 39 ].…”

Bone Marrow Environment in Metastatic Neuroblastoma

“…Further studies are needed to clarify whether MSC favors BM infiltration by NB cells or NB cells alter the MSC differentiation process. Moreover, the use of mesenchymal cells as tumor-selective delivery vehicles for therapeutic compounds and oncolytic viruses needs to be reconsidered [ 84 ].…”

The role of MSCs and CAR-MSCs in cellular immunotherapy

“…MSCs can migrate to tumor sites and inflamed sites as damaged tissues expressing ligands or specific receptors that stimulate the trafficking, recruitment, adhesion and extravasation of MSCs [ 138 ]. MSCs-derived exosomes play vital roles in cancer therapy resistance, including resistance to immunotherapy, chemotherapy, radiotherapy, and targeted therapy [ 69 , 139 , 140 ].…”