Background aims: Adipose-derived mesenchymal stromal cells (AD-MSCs) have high proliferative capacity and ability to secrete trophic factors. Although intra-arterial (IA) transplantation of stem cells induces efficient engraftment to the host brain, it is unclear whether engrafted cells exert their long-term therapeutic effects through a bystander mechanism or a cell replacement mechanism. Methods: After induction of ischemia in rats by middle cerebral artery occlusion, we transplanted human AD-MSCs into their carotid arteries with the use of a micro-needle, and we then investigated the therapeutic effects during the early and late phases of ischemia by means of in vivo magnetic resonance imaging, functional and histological analyses. Results: During the early phase of cerebral ischemia, IA transplantation of AD-MSCs attenuated inflammation and enhanced endogenous neurogenesis. Transplanted animals showed a marked improvement in functional tests during the early phase of cerebral ischemia that was less prominent but still significant during the late phase of cerebral ischemia. Although the transplanted cells effectively migrated to the infarct area, only a small number of engrafted cells survived at 8 weeks after transplantation and differentiated into neuronal, glial and endothelial cells. Conclusions: IA transplantation of human AD-MSCs provides an effective therapeutic modality in a rodent model of stroke, of which the main effects are mediated by a bystander mechanism at the early phase of ischemia.
Bibliographical noteFunding Information:
We are grateful to the MRI facility located in the Division of Magnetic Resonance at the Korea Basic Science Institute (Ochang, Korea). This study was supported by grants from the Korea Healthcare Technology R&D Project , Ministry for Health, Welfare & Family Affairs, Republic of Korea ( HI11C0981 and HI12C1817 ) and the Next-Generation BioGreen 21 Program (No. PJ010002012014), the Rural Development Administration, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Cell Biology
- Cancer Research