Neuroprotective Effect of 4T1 and Sertoli Cells Co-Transplantation in Animal Model of Brain Ischemia

Abstract

Aim: Introducing neurotrophic factors are among several new approaches to enhance neural resistance to the ischemic condition. Cancer cells such as 4T1 are one of the strongest cells with high viability in transplanted area. 4T1 cells are invasive breast carcinoma cells derived from spontaneous tumors in mouse Balb/C which their pathologic effects are limited to Balb/C species. Sertoli cells (SCs) can be a proper candidate for increasing transplanted cells survival. These cells not only suppress the immune system, but also secret growth factors. The aim of this study is to evaluate the possible neuroprotective effect of 4T1 transplantation on middle cerebral artery occlusion (MCAO) rat model alone and with SCs co-transplanted. Material and Methods: Rats were divided into five experimental groups: control, sham, SCs, 4T1 and 4T1+SCs treated groups. Cells were transplanted into the right striatum by using stereotaxic surgery. Ischemic surgery was done after five days. 24 hours after reperfusion, neurological severity score, infarct volume, brain edema, and blood-brain barrier permeability were assessed in different areas of the brain including cortex, striatum and piriform cortex-amygdala (Pir-Amy). Results: This study demonstrates that SCs and 4T1 transplantation ameliorate neurological deficits and reduce infarct volume, brain edema and blood-brain barrier permeability compared to the control group. Conclusion: Introducing cancer cell transplantation as a source of neurotrophic factors to enhance neural survival can be a new approach in cell therapy.

Keywords: Sertoli cells, Middle cerebral artery occlusion, Blood-brain barrier, Brain edema, Cell transplantation