Neuroprotective effect of mesenchymal stem cell through complement component 3 downregulation after transient focal cerebral ischemia in mice.
Bone marrow-derived mesenchymal stem cells (MSCs) are used in stroke treatment despite the poor understanding of its mode of action. The immune suppressive and anti-inflammatory properties of MSCs possibly play important roles in regulating neuroinflammation after stroke. We investigated whether MSCs reduce the inflammatory complement component 3 (C3) levels, thus, providing neuroprotection during stroke. Mice were subjected to transient focal cerebral ischemia (tFCI), after which MSCs were intravenously injected. The infarct volume of the brain was reduced in MSC-injected tFCI mice, and C3 expression was significantly reduced in both the brain and the blood. Additionally, the profiles of other inflammatory mediators demonstrated neuroprotective changes in the MSCs-treated group. In order to analyze the effect of MSCs on neurons during cerebral ischemia, primary cortical neurons were co-cultured with MSCs under oxygen-glucose deprivation (OGD). Primary neurons co-cultured with MSCs exhibited reduced levels of C3 expression and increased protection against OGD, indicating that treatment with MSCs reduces excessive C3 expression and rescues ischemia-induced neuronal damage. Our finding suggests that reduction of C3 expression by MSCs can help to ameliorate ischemic brain damage, offering a new neuroprotective strategy in stroke therapy.
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
Hye-Seon
HS
Jung
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
Si-Yeon
SY
Jeong
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
Jiwon
J
Yang
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
So-Dam
SD
Kim
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
Baojin
B
Zhang
Translational Research Center, Department of Molecular Biomedicine, Inha Research Institute for Medical Science, Incheon, Republic of Korea.
Hyun Seung
HS
Yoo
Translational Research Center, Department of Molecular Biomedicine, Inha Research Institute for Medical Science, Incheon, Republic of Korea.
Sun U
SU
Song
Translational Research Center, Department of Molecular Biomedicine, Inha Research Institute for Medical Science, Incheon, Republic of Korea; Convergent Research Center for Metabolism and Immunoregulation, Inha University School of Medicine, Incheon, Republic of Korea. Electronic address: msjeon@inha.ac.kr.
Myung-Shin
MS
Jeon
College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea. Electronic address: yssong@sookmyung.ac.kr.
Yun Seon
YS
Song
D000818:Animals; D015687:Cell Hypoxia; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003176:Complement C3 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005947:Glucose / Q000172:deficiency; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism
D003176:Complement C3; D016207:Cytokines; D008869:Microtubule-Associated Proteins; D005947:Glucose; D010100:Oxygen
Cerebral ischemia; Complement component 3; Mesenchymal stem cell; Neuroprotection; Oxygen glucose deprivation