PMID- 31012325 OWN - NLM STAT- MEDLINE DCOM- 20200831 LR - 20200831 IS - 1555-3892 (Electronic) IS - 0963-6897 (Print) IS - 0963-6897 (Linking) VI - 28 IP - 7 DP - 2019 Jul TI - Co-Transplantation of Human Umbilical Cord Mesenchymal Stem Cells and Human Neural Stem Cells Improves the Outcome in Rats with Spinal Cord Injury. PG - 893-906 LID - 10.1177/0963689719844525 [doi] AB - Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) are promising graft materials for cell therapies in spinal cord injury (SCI) models. Previous studies have demonstrated that MSCs can regulate the microenvironment of NSCs and promote their survival rate. Furthermore, several studies indicate that MSCs can reduce stem cell transplantation-linked tumor formation. To our knowledge, no previous studies have determined whether co-transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) and human neural stem cells (hNSCs) could improve the outcome in rats with SCI. Therefore, we investigated whether the transplantation of hUC-MSCs combined with hNSCs through an intramedullary injection can improve the outcome of rats with SCI, and explored the underlying mechanisms. In this study, a moderate spinal cord contusion model was established in adult female Wistar rats using an NYU impactor. In total, 108 spinal cord-injured rats were randomly selected and divided into the following five groups: 1) hUC-MSCs group, 2) hNSCs group, 3) hUC-MSCs+hNSCs group, 4) PBS (control) group, and 5) a Sham group. Basso, Beattie and Bresnahan (BBB) behavioral test scores were used to evaluate the motor function of all animals before and after the SCI weekly through the 8th week. Two weeks after transplantation, some rats were sacrificed, immunofluorescence and immunohistochemistry were performed to evaluate the survival and differentiation of the transplanted stem cells, and brain-derived neurotrophic factor (BDNF) was detected by ELISA in the injured spinal cords. At the end of the experiment, we evaluated the remaining myelin sheath and anterior horn neurons in the injured spinal cords using Luxol Fast Blue (LFB) staining. Our results demonstrated that the surviving stem cells in the hUC-MSCs+hNSCs group were significantly increased compared with those in the hUC-MSCs alone and the hNSCs alone groups 2 weeks post-transplantation. Furthermore, the results of the BBB scores and the remaining myelin sheath evaluated via LFB staining in the injured spinal cords demonstrated that the most significantly improved outcome occurred in the hUC-MSCs+hNSCs group. The hUC-MSCs alone and the hNSCs alone groups also had a better outcome compared with that of the PBS-treated group. In conclusion, the present study demonstrates that local intramedullary subacute transplantation of hUC-MSCs, hNSCs, or hUC-MSCs+hNSCs significantly improves the outcome in an in vivo moderate contusion SCI model, and that co-transplantation of hUC-MSCs and hNSCs displayed the best outcome in our experiment. FAU - Sun, Lei AU - Sun L AUID- ORCID: 0000-0001-5104-9996 AD - 1 Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, China. AD - 2 Department of Orthopaedics, Taian City Central Hospital, Shandong, China. AD - 3 Department of Orthopaedics, Qian Fo Shan Hospital, Shandong University, Jinan, China. FAU - Wang, Fan AU - Wang F AD - 3 Department of Orthopaedics, Qian Fo Shan Hospital, Shandong University, Jinan, China. FAU - Chen, Heng AU - Chen H AD - 4 R&D, Cell and Tissue Bank of Shandong Province, Jinan, China. FAU - Liu, Dong AU - Liu D AD - 4 R&D, Cell and Tissue Bank of Shandong Province, Jinan, China. FAU - Qu, Tingyu AU - Qu T AD - 5 Department of Psychiatry, College of Medicine, University of Illinois at Chicago, USA. FAU - Li, Xiaofeng AU - Li X AD - 1 Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, China. FAU - Xu, Daxia AU - Xu D AD - 1 Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, China. FAU - Liu, Feng AU - Liu F AD - 2 Department of Orthopaedics, Taian City Central Hospital, Shandong, China. FAU - Yin, Zhanmin AU - Yin Z AD - 2 Department of Orthopaedics, Taian City Central Hospital, Shandong, China. FAU - Chen, Yunzhen AU - Chen Y AUID- ORCID: 0000-0001-8447-9001 AD - 1 Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190423 PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 SB - IM MH - Animals MH - Cell Differentiation/physiology MH - Female MH - Humans MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*cytology MH - Neural Stem Cells/*cytology MH - Rats MH - Rats, Wistar MH - Spinal Cord Injuries/*therapy MH - Umbilical Cord/*cytology PMC - PMC6719499 OTO - NOTNLM OT - human neural stem cells OT - human umbilical cord mesenchymal stem cells OT - intramedullary transplantation OT - spinal cord injury COIS- Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2019/04/24 06:00 MHDA- 2020/09/01 06:00 PMCR- 2019/07/01 CRDT- 2019/04/24 06:00 PHST- 2019/04/24 06:00 [pubmed] PHST- 2020/09/01 06:00 [medline] PHST- 2019/04/24 06:00 [entrez] PHST- 2019/07/01 00:00 [pmc-release] AID - 10.1177_0963689719844525 [pii] AID - 10.1177/0963689719844525 [doi] PST - ppublish SO - Cell Transplant. 2019 Jul;28(7):893-906. doi: 10.1177/0963689719844525. Epub 2019 Apr 23.