title: Early Immunomodulation by Intravenously Transplanted Mesenchymal Stem Cells Promotes Functional Recovery in Spinal Cord Injured Rats.
abstract: Although intravenous administration of mesenchymal stem cells (MSCs) can enhance functional recovery after spinal cord injury (SCI), the underlying mechanisms have to be elucidated. In this study, we explored the mechanisms for functional recovery in SCI rats after intravenous transplantation of MSCs derived from human umbilical cord blood. Sprague-Dawley rats were randomly assigned to receive either MSCs (1 × 10(6) cells/0.5 ml) or PBS into the tail vein immediately after SCI. They were then evaluated by the Basso-Beattie-Bresnahan (BBB) locomotor rating scale weekly for 8 weeks and by somatosensory evoked potentials (SSEPs) 8 weeks after transplantation. MSC-treated rats showed a modest but significant improvement in BBB scores and latencies of SSEPs, compared with PBS controls. When human-specific Alu element was measured in the spinal cord, it was detected only 1 h after transplantation, suggesting transient engraftment of MSCs. Inflammatory cytokines were also determined using RT-PCR or Western blot in spinal cord extracts. In MSC-treated rats, the level of proinflammatory cytokine IL-1β was decreased, but that of anti-inflammatory cytokine IL-10 was increased. MSCs also immediately suppressed IL-6 at 1 h posttransplantation. However, the response of IL-6, which has an immunoregulatory role, was increased 1-3 days after transplantation. In addition, we quantified microglia/macrophage stained with Iba-1 around the damaged spinal cord using immunohistochemistry. A proportion of activated microglia and macrophages in total Iba-1(+) cells was significantly decreased in MSC-treated rats, compared with PBS controls. These results suggest that early immunomodulation by intravenously transplanted MSCs is a potential underlying mechanism for functional recovery after SCI.
authors.affiliation: Department & Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea; †Clinical Research Center, Yonsei University Health System, Seoul, Korea.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Seo
authors.affiliation: ‡ Biomedical Research Institute, Lifeliver Inc , Suwon , Korea.
authors.forename: In Keun
authors.initials: IK
authors.lastname: Jang
authors.affiliation: § Graduate School of Biomedical Science and Engineering College of Medicine, Hanyang University , Seoul , Korea.
authors.forename: Hyongbum
authors.initials: H
authors.lastname: Kim
authors.affiliation: ‡ Biomedical Research Institute, Lifeliver Inc , Suwon , Korea.
authors.forename: Mal Sook
authors.initials: MS
authors.lastname: Yang
authors.affiliation: ‡ Biomedical Research Institute, Lifeliver Inc , Suwon , Korea.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: ‡ Biomedical Research Institute, Lifeliver Inc , Suwon , Korea.
authors.forename: Hyo Eun
authors.initials: HE
authors.lastname: Kim
authors.affiliation: ‡ Biomedical Research Institute, Lifeliver Inc , Suwon , Korea.
authors.forename: Yong-Woo
authors.initials: YW
authors.lastname: Eom
authors.affiliation: ‡ Biomedical Research Institute, Lifeliver Inc , Suwon , Korea.
authors.forename: Doo-Hoon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department & Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea; †Clinical Research Center, Yonsei University Health System, Seoul, Korea; ¶Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Korea.
authors.forename: Ji Hea
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Department & Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea; †Clinical Research Center, Yonsei University Health System, Seoul, Korea; #Graduate Program of Nano Science and Technology, Yonsei University, Seoul, Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: * Department of Laboratory Medicine, Yonsei University College of Medicine , Seoul , Korea.
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Kim
authors.affiliation: Department & Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea; †Clinical Research Center, Yonsei University Health System, Seoul, Korea; #Graduate Program of Nano Science and Technology, Yonsei University, Seoul, Korea.
authors.forename: Sung-Rae
authors.initials: SR
authors.lastname: Cho
keywords: Functional recovery; Immunomodulation; Mesenchymal stem cells (MSCs); Spinal cord injury; Transplantation