PMID- 33821317 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20220813 IS - 0942-0940 (Electronic) IS - 0001-6268 (Print) IS - 0001-6268 (Linking) VI - 163 IP - 8 DP - 2021 Aug TI - Exosomes secreted from sonic hedgehog-modified bone mesenchymal stem cells facilitate the repair of rat spinal cord injuries. PG - 2297-2306 LID - 10.1007/s00701-021-04829-9 [doi] AB - BACKGROUND: Spinal cord injuries (SCIs) can cause a loss of neurons and associated sensory and motor functionality below the injured site. No approaches to treating SCIs in humans have been developed to date. Exosomes are extracellular vesicles that hold promise as a potential therapeutic modality when treating such injuries. The present study was thus designed to determine whether sonic hedgehog (Shh)-overexpressing bone mesenchymal stem cell (BMSC)-derived exosomes were protective in the context of SCIs. METHODS: Exosomes were extracted from control or Shh lentivirus-transduced BMSCs, yielding respective BMSC-Exo and BMSC-Shh-Exo preparations which were intravenously injected into SCI model rats. Shh expression in spinal cord tissues in these animals was then assessed via immunohistochemical staining, while Basso-Beattie-Bresnahan (BBB) scores were utilized to measure high limb motor function. Neuronal damage and regeneration within the spinal cord were additionally evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Nissl, hematoxylin and eosin, and immunofluorescent staining. RESULTS: Both BMSC-Exo and BMSC-Shh-Exo preparations significantly increased Shh expression in the spinal cord of SCI model rats and improved BBB scores in these treated animals, while also increasing the frequencies of Nissl- and NeuN-positive neurons are reducing the numbers of apoptotic and GFAP-positive neurons. While both treatments yielded some degree of benefit to treated animals relative to untreated controls, BMSC-Shh-Exos were more beneficial than were control BMSC-Exos. CONCLUSIONS: Shh-overexpressing BMSC-derived exosomes represent an effective treatment that can facilitate SCI repair in rats. CI - (c) 2021. The Author(s). FAU - Jia, Yijia AU - Jia Y AD - Department of Spine Surgery, Guizhou Province Osteological Hospital, 123 Shachong South Street, Nanming District, Guiyang, 550002, Guizhou Province, China. FAU - Lu, Tingsheng AU - Lu T AD - Department of Spine Surgery, Guizhou Province Osteological Hospital, 123 Shachong South Street, Nanming District, Guiyang, 550002, Guizhou Province, China. FAU - Chen, Qiling AU - Chen Q AD - Department of Spine Surgery, Guizhou Province Osteological Hospital, 123 Shachong South Street, Nanming District, Guiyang, 550002, Guizhou Province, China. FAU - Pu, Xingwei AU - Pu X AD - Department of Spine Surgery, Guizhou Province Osteological Hospital, 123 Shachong South Street, Nanming District, Guiyang, 550002, Guizhou Province, China. FAU - Ji, Linsong AU - Ji L AD - Department of Spine Surgery, Guizhou Province Osteological Hospital, 123 Shachong South Street, Nanming District, Guiyang, 550002, Guizhou Province, China. FAU - Yang, Jianwen AU - Yang J AD - Department of Spine Surgery, Guizhou Province Osteological Hospital, 123 Shachong South Street, Nanming District, Guiyang, 550002, Guizhou Province, China. FAU - Luo, Chunshan AU - Luo C AD - Department of Spine Surgery, Guizhou Province Osteological Hospital, 123 Shachong South Street, Nanming District, Guiyang, 550002, Guizhou Province, China. jiayijia2192@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210405 PL - Austria TA - Acta Neurochir (Wien) JT - Acta neurochirurgica JID - 0151000 RN - 0 (Hedgehog Proteins) SB - IM MH - Animals MH - *Exosomes MH - Hedgehog Proteins MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells MH - Rats MH - Rats, Sprague-Dawley MH - Recovery of Function MH - Spinal Cord MH - *Spinal Cord Injuries/therapy PMC - PMC8270837 OTO - NOTNLM OT - BMSCs OT - Exosomes OT - Sonic hedgehog OT - Spinal cord injury COIS- The authors declare no competing interests. EDAT- 2021/04/07 06:00 MHDA- 2021/10/21 06:00 PMCR- 2021/04/05 CRDT- 2021/04/06 05:56 PHST- 2021/01/05 00:00 [received] PHST- 2021/03/23 00:00 [accepted] PHST- 2021/04/07 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/04/06 05:56 [entrez] PHST- 2021/04/05 00:00 [pmc-release] AID - 10.1007/s00701-021-04829-9 [pii] AID - 4829 [pii] AID - 10.1007/s00701-021-04829-9 [doi] PST - ppublish SO - Acta Neurochir (Wien). 2021 Aug;163(8):2297-2306. doi: 10.1007/s00701-021-04829-9. Epub 2021 Apr 5.