Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

Purpose: “Naked” human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro-protective substance glucagon-like peptide-1 (GLP-1). Methods: Thirty two Sprague-Dawley rats were randomized to five groups: controls (no CCI), CCI-only, CCI + eMSC, CCI + GLP-1 eMSC, and CCI + empty capsules. On day 14, cisternal cerebro-spinal fluid (CSF) was sampled for measurement of GLP-1 concentration. Brains were immuno-histochemically assessed using specific antibody staining for NeuN, MAP-2 and GFAP. In another nine healthy rats, in vitro Results: GLP-1 production rates were measured from cells explanted after 2, 7 and 14 days. GLP-1 production rate in transfected cells, before implantation, was 7.03 fmol/capsule/h. Cells were still secreting GLP-1 at a rate of 3.68 ± 0.49, 2.85 ± 0.45 and 3.53 ± 0.55 after 2, 7 and 14 days, respectively. In both of the stem cell treated CCI groups, hippocampal cell loss was reduced, along with an attenuation of cortical neuronal and glial abnormalities, as measured by MAP-2 and GFAP expression. The effects were more pronounced in animals treated with GLP-1 secreting eMSC. This group displayed an increased CSF level of GLP-1 (17.3 ± 3.4 pM). Conclusions: Hippocampal neuronal cell loss, and cortical glial and neuronal cyto-skeletal abnormalities, after CCI are reduced following transplantation of encapsulated eMSC. These effects were augmented by GLP-1 transfected eMSC.