PMID- 35457084 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220716 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 8 DP - 2022 Apr 12 TI - Significant Therapeutic Effects of Adult Human Neural Stem Cells for Spinal Cord Injury Are Mediated by Monocyte Chemoattractant Protein-1 (MCP-1). LID - 10.3390/ijms23084267 [doi] LID - 4267 AB - The limited capability of regeneration in the human central nervous system leads to severe and permanent disabilities following spinal cord injury (SCI) while patients suffer from no viable treatment option. Adult human neural stem cells (ahNSCs) are unique cells derived from the adult human brain, which have the essential characteristics of NSCs. The objective of this study was to characterize the therapeutic effects of ahNSCs isolated from the temporal lobes of focal cortical dysplasia type IIIa for SCI and to elucidate their treatment mechanisms. Results showed that the recovery of motor functions was significantly improved in groups transplanted with ahNSCs, where, in damaged regions of spinal cords, the numbers of both spread and regenerated nerve fibers were observed to be higher than the vehicle group. In addition, the distance between neuronal nuclei in damaged spinal cord tissue was significantly closer in treatment groups than the vehicle group. Based on an immunohistochemistry analysis, those neuroprotective effects of ahNSCs in SCI were found to be mediated by inhibiting apoptosis of spinal cord neurons. Moreover, the analysis of the conditioned medium (CM) of ahNSCs revealed that such neuroprotective effects were mediated by paracrine effects with various types of cytokines released from ahNSCs, where monocyte chemoattractant protein-1 (MCP-1, also known as CCL2) was identified as a key paracrine mediator. These results of ahNSCs could be utilized further in the preclinical and clinical development of effective and safe cell therapeutics for SCI, with no available therapeutic options at present. FAU - Kim, Chung Kwon AU - Kim CK AD - Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea. AD - Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. FAU - Won, Jeong-Seob AU - Won JS AD - Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea. AD - Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea. AD - Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. AD - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea. FAU - An, Jae Yeol AU - An JY AD - Department of Anatomy, Seoul National University College of Medicine, Seoul 03880, Korea. AD - Healthcare Division, Partners Investment Co., Ltd., Seoul 06152, Korea. FAU - Lee, Ho Jin AU - Lee HJ AD - Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. AD - Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. FAU - Nam, Ah-Jin AU - Nam AJ AD - Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. FAU - Nam, Hyun AU - Nam H AD - Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea. AD - Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea. AD - Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. AD - Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. AD - Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea. FAU - Lee, Ji Yeoun AU - Lee JY AD - Department of Anatomy, Seoul National University College of Medicine, Seoul 03880, Korea. AD - Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 03080, Korea. FAU - Lee, Kyung-Hoon AU - Lee KH AD - Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. AD - Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. FAU - Lee, Sun-Ho AU - Lee SH AUID- ORCID: 0000-0003-3357-4329 AD - Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea. AD - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea. AD - Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea. FAU - Joo, Kyeung Min AU - Joo KM AUID- ORCID: 0000-0003-2750-405X AD - Medical Innovation Technology Inc. (MEDINNO Inc.), Ace High-End Tower Classic 26, Seoul 08517, Korea. AD - Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea. AD - Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea. AD - Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. AD - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea. AD - Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. LA - eng GR - 2016R1A5A2945889/National Research Foundation of Korea/ GR - 2019R1F1A1060243/National Research Foundation of Korea/ GR - 2020R1A6C101A191/Korea Basic Science Institute/ GR - SMX1161411/Samsung Biomedical Research Institute grant/ PT - Journal Article DEP - 20220412 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Chemokine CCL2) RN - 0 (Neuroprotective Agents) SB - IM MH - Adult MH - Chemokine CCL2 MH - Humans MH - *Neural Stem Cells/transplantation MH - *Neuroprotective Agents/therapeutic use MH - Recovery of Function/physiology MH - Spinal Cord MH - *Spinal Cord Injuries/drug therapy PMC - PMC9029183 OTO - NOTNLM OT - dose escalation OT - lateral ventricle OT - monocyte chemoattractant protein-1 OT - neural stem cell OT - spinal cord injury COIS- The authors declare no conflicts of interest. EDAT- 2022/04/24 06:00 MHDA- 2022/04/27 06:00 PMCR- 2022/04/12 CRDT- 2022/04/23 01:11 PHST- 2022/02/17 00:00 [received] PHST- 2022/03/31 00:00 [revised] PHST- 2022/04/11 00:00 [accepted] PHST- 2022/04/23 01:11 [entrez] PHST- 2022/04/24 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/04/12 00:00 [pmc-release] AID - ijms23084267 [pii] AID - ijms-23-04267 [pii] AID - 10.3390/ijms23084267 [doi] PST - epublish SO - Int J Mol Sci. 2022 Apr 12;23(8):4267. doi: 10.3390/ijms23084267.