Intra-arterial transplantation of low-dose stem cells provides functional recovery without adverse effects after stroke.
Cell transplantation therapy for cerebral infarction has emerged as a promising treatment to reduce brain damage and enhance functional recovery. We previously reported that intra-arterial delivery of bone marrow mesenchymal stem cells (MSCs) enables superselective cell administration to the infarct area and results in significant functional recovery after ischemic stroke in a rat model. However, to reduce the risk of embolism caused by the transplanted cells, an optimal cell number should be determined. At 24 h after middle cerebral artery occlusion and reperfusion, we administered human MSCs (low dose: 1 × 10(4) cells; high dose: 1 × 10(6) cells) and then assessed functional recovery, inflammatory responses, cell distribution, and mortality. Rats treated with high- or low-dose MSCs showed behavioral recovery. At day 8 post-stroke, microglial activation was suppressed significantly, and interleukin (IL)-1β and IL-12p70 were reduced in both groups. Although high-dose MSCs were more widely distributed in the cortex and striatum of rats, the degree of intravascular cell aggregation and mortality was significantly higher in the high-dose group. In conclusion, selective intra-arterial transplantation of low-dose MSCs has anti-inflammatory effects and reduces the adverse effects of embolic complication, resulting in sufficient functional recovery of the affected brain.
Department of Neurosurgery, School of Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.
Yuhtaka
Y
Fukuda
Department of Neurosurgery, School of Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan. nobstanford@gmail.com.
Nobutaka
N
Horie
Department of Molecular Microbiology and Immunology, School of Medicine, Nagasaki University, Nagasaki, Japan.
Katsuya
K
Satoh
Department of Neurosurgery, School of Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.
Susumu
S
Yamaguchi
Department of Neurosurgery, School of Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.
Youichi
Y
Morofuji
Department of Neurosurgery, School of Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.
Takeshi
T
Hiu
Department of Neurosurgery, School of Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.
Tsuyoshi
T
Izumo
Department of Neurosurgery, School of Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.
Kentaro
K
Hayashi
Department of Molecular Microbiology and Immunology, School of Medicine, Nagasaki University, Nagasaki, Japan.
Noriyuki
N
Nishida
Department of Neurosurgery, School of Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.
Izumi
I
Nagata
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020521:Stroke / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D055815:Young Adult