Neuroprotective effect of secreted factors from human adipose stem cells in a rat stroke model

Abstract

Objectives

Recent evidence shows that stem cells exert neuroprotective effect through the secretion of immune modulatory, neurotrophic factors. We aimed to assess the neuroprotective effect of selected recombinant factors (RFs) detected in human adipose stem cell (hASC)-conditioned medium (CM), in a rat ischemic stroke model.

Methods

Ischemic stroke was induced in Sprague-Dawley rats using 2 h transient middle cerebral artery occlusion (MCAO). One hour after reperfusion, the vehicle (Dulbecco’s modified Eagle medium; DMEM), concentrated CM, and selected RFs mixed with DMEM were administered intracerebroventricularly to each group (N = 14, 15, and 16, respectively). Rats were sacrificed 24 h after MCAO.

Results

IL-6, VEGF, HGF, and BDNF were detected in hASC-CM. At 24 h post-MCAO, the CM and RF groups both showed significantly better sensorimotor neurological test scores than the control group. The infarct volume was significantly lower in both the CM and RF groups than in the control group. The number of TUNEL-positive apoptotic cells was reduced, whereas HSP70 expression was enhanced in the peri-infarct area in both the CM and RF groups. Moreover, hASC-CM and RFs reduced IκB phosphorylation and influenced bcl-2 and bax protein expression.

Conclusions

Our results suggest that RFs, selected from hASC-CM, may exert a neuroprotective effect in an ischemic stroke rat model that is comparable to the neuroprotective effect of full hASC-CM. The therapeutic effects of the RFs may be mediated by an anti-inflammatory mechanism and cell apoptosis inhibition. Hence, treatment with RFs can be considered a feasible substitute for stem cell therapy after stroke.

Keywords:

• Stroke
• stem cells
• neuroprotection
• rats
• recombinant factors