PMID- 35611987 OWN - NLM STAT- MEDLINE DCOM- 20221214 LR - 20230105 IS - 1557-9042 (Electronic) IS - 0897-7151 (Print) IS - 0897-7151 (Linking) VI - 39 IP - 23-24 DP - 2022 Dec TI - Enhanced Network in Corticospinal Tracts after Infused Mesenchymal Stem Cells in Spinal Cord Injury. PG - 1665-1677 LID - 10.1089/neu.2022.0106 [doi] AB - Although limited spontaneous recovery occurs after spinal cord injury (SCI), current knowledge reveals that multiple forms of axon growth in spared axons can lead to circuit reorganization and a detour or relay pathways. This hypothesis has been derived mainly from studies of the corticospinal tract (CST), which is the primary descending motor pathway in mammals. The major CST is the dorsal CST (dCST), being the major projection from cortex to spinal cord. Two other components often called "minor" pathways are the ventral and the dorsal lateral CSTs, which may play an important role in spontaneous recovery. Intravenous infusion of mesenchymal stem cells (MSCs) provides functional improvement after SCI with an enhancement of axonal sprouting of CSTs. Detailed morphological changes of CST pathways, however, have not been fully elucidated. The primary objective was to evaluate detailed changes in descending CST projections in SCI after MSC infusion. The MSCs were infused intravenously one day after SCI. A combination of adeno-associated viral vector (AAV), which is an anterograde and non-transsynaptic axonal tracer, was injected 14 days after SCI induction. The AAV with advanced tissue clearing techniques were used to visualize the distribution pattern and high-resolution features of the individual axons coursing from above to below the lesion. The results demonstrated increased observable axonal connections between the dCST and axons in the lateral funiculus, both rostral and caudal to the lesion core, and an increase in observable axons in the dCST below the lesion. This increased axonal network could contribute to functional recovery by providing greater input to the spinal cord below the lesion. FAU - Hirota, Ryosuke AU - Hirota R AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Sasaki, Masanori AU - Sasaki M AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Neurology, and Yale University School of Medicine, New Haven, Connecticut, USA. FAU - Kataoka-Sasaki, Yuko AU - Kataoka-Sasaki Y AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Oshigiri, Tsutomu AU - Oshigiri T AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Kurihara, Kota AU - Kurihara K AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Fukushi, Ryunosuke AU - Fukushi R AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Oka, Shinichi AU - Oka S AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Ukai, Ryo AU - Ukai R AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Yoshimoto, Mitsunori AU - Yoshimoto M AD - Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Kocsis, Jeffery D AU - Kocsis JD AD - Department of Neurology, and Yale University School of Medicine, New Haven, Connecticut, USA. AD - Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut, USA. AD - Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, Connecticut, USA. FAU - Yamashita, Toshihiko AU - Yamashita T AD - Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Honmou, Osamu AU - Honmou O AD - Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Department of Neurology, and Yale University School of Medicine, New Haven, Connecticut, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20220714 PL - United States TA - J Neurotrauma JT - Journal of neurotrauma JID - 8811626 SB - IM MH - Animals MH - Pyramidal Tracts/physiology MH - *Spinal Cord Injuries MH - Recovery of Function/physiology MH - Axons/pathology MH - Spinal Cord/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - Nerve Regeneration/physiology MH - Mammals PMC - PMC9734021 OTO - NOTNLM OT - axon tracing OT - mesenchymal stem cell OT - spinal cord injury COIS- No competing financial interests exist. EDAT- 2022/05/26 06:00 MHDA- 2022/12/15 06:00 PMCR- 2022/11/30 CRDT- 2022/05/25 08:24 PHST- 2022/05/26 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] PHST- 2022/05/25 08:24 [entrez] PHST- 2022/11/30 00:00 [pmc-release] AID - 10.1089/neu.2022.0106 [pii] AID - 10.1089/neu.2022.0106 [doi] PST - ppublish SO - J Neurotrauma. 2022 Dec;39(23-24):1665-1677. doi: 10.1089/neu.2022.0106. Epub 2022 Jul 14.