Rat multipotent mesenchymal stromal cells lack long-distance tropism to three different rat glioma models.

In English BACKGROUND:: Viral gene therapy of malignant brain tumors has been restricted due to the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy. OBJECTIVE:: To investigate MSC migration in detail following intratumoral and extratumoral implantation using syngeneic and orthotopic glioma models. METHODS:: Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance to rat gliomas. RESULTS:: We found no evidence of long-distance MSC migration through the intact striatum towards syngeneic D74(RG2), N32 and N29 gliomas in the ipsilateral hemisphere, or across the corpus callosum to gliomas located in the contralateral hemisphere. Following intratumoral injection, MSCs migrated extensively, and specifically, within N32 gliomas. MSCs did not proliferate within tumors, suggesting a low risk of malignant transformation of in vivo grafted cell vectors. Using a model for surgical glioma resection, we found that intratumorally grafted MSCs migrate efficiently within glioma remnants following partial surgical resection. CONCLUSION:: The findings point to limitations for the use of MSCs as vectors in glioma gene therapy, although intratumoral MSC implantation provides a dense and tumor specific vector distribution.