Aggregation of human mesenchymal stem cells enhances survival and efficacy in stroke treatment

In this study, we report the effects of short-term preconditioning of hMSCs via three-dimensional (3D) aggregation on stroke lesion recovery after intra-arterial (IA) transplantation of 3D aggregate-derived hMSCs (Agg-D hMSCs) in a transient middle cerebral artery occlusion (MCAO) stroke model. Compared with two-dimensional (2D) monolayer culture, Agg-D hMSCs exhibited increased resistance to ischemic stress, secretory function and therapeutic outcome. Short-term preconditioning via 3D aggregation reconfigured hMSC energy metabolism and altered redox cycle, which activated the PI3K/AKT pathway and enhanced resistance to in vitro oxidative stress. Analysis of transplanted hMSCs in MCAO rats using ultra-high-field magnetic resonance imaging at 21.1 T showed increased hMSC persistence and stroke lesion reduction by sodium (23Na) imaging in the Agg-D hMSC group compared with 2D hMSC control. Behavioral analyses further revealed functional improvement in MCAO animal treated with Agg-D hMSCs compared with saline control. Together, the results demonstrated the improved outcome for Agg-D hMSCs in the MCAO model and suggest short-term 3D aggregation as an effective preconditioning strategy for hMSC functional enhancement in stroke treatment.
Source: Cytotherapy - Category: Cytology Source Type: research