Seung-Hun Oh1, Chunggab Choi2, Da-Jeong Chang2, Dong-Ah Shin3, Nayeon Lee2, Iksoo Jeon2, Jong-Hyuk Sung4, Hyunseung Lee5, Kwan-Soo Hong5, Jung Jae Ko2, Jihwan Song6. 1. Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea. 2. Department of Biomedical Science and CHA Stem Cell Institute, College of Life Science, CHA University, Seongnam, Republic of Korea. 3. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. College of Pharmacy, Yonsei University, Incheon, Republic of Korea. 5. Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Republic of Korea. 6. Department of Biomedical Science and CHA Stem Cell Institute, College of Life Science, CHA University, Seongnam, Republic of Korea. Electronic address: jsong@cha.ac.kr.
Abstract
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.
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.
Authors: Piotr Walczak; Joanna Wojtkiewicz; Adam Nowakowski; Aleksandra Habich; Piotr Holak; Jiadi Xu; Zbigniew Adamiak; Moussa Chehade; Monica S Pearl; Philippe Gailloud; Barbara Lukomska; Wojciech Maksymowicz; Jeff Wm Bulte; Miroslaw Janowski Journal: J Cereb Blood Flow Metab Date: 2016-01-01 Impact factor: 6.200