title: Preconditioning in lowered oxygen enhances the therapeutic potential of human umbilical mesenchymal stem cells in a rat model of spinal cord injury.
abstract: Human umbilical cord mesenchymal stem cells (UCMSCs) have recently been shown to hold great therapeutic potential for the treatment of spinal cord injury (SCI). However, the number of engrafted cells has been shown to decrease dramatically post-transplantation. Physioxia is known to enhance the paracrine properties and immune modulation of stem cells, a notion that has been applied in many clinical settings. We therefore hypothesized that preconditioning of UCMSCs in physioxic environment would enhance the regenerative properties of these cells in the treatment of rat SCI. UCMSCs were pretreated with either atmospheric normoxia (21% O2, N-UCMSC) or physioxia (5% O2, P-UCMSC). The MSCs were characterized using flow cytometry, immunocytochemistry, and real-time polymerase chain reaction. Furthermore, 10(5) N-UCMSC or P-UCMSC were injected into the injured spinal cord immediately after SCI, and locomotor function as well as cellular, molecular and pathological changes were compared between the groups. We found that N-UCMSC and P-UCMSC displayed similar surface protein expression. P-UCMSC grew faster, while physioxia up-regulated the expression of trophic and growth factors, including hepatocyte growth factor (HGF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor(VEGF), in UCMSCs. Compared to N-UCMSC, treatment with P-UCMSC was associated with marked changes in the SCI environment, with a significant increase in axonal preservation and a decrease in the number of caspase-3+ cells and ED-1+ macrophages. These changes were accompanied by improved functional recovery. Thus, the present study indicated that preculturing UCMSCs under 5% lowered oxygen physioxic conditions prior to transplantation improves their therapeutic potential for the treatment of SCI in rats.
authors.affiliation: Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye road, 510282 Guangzhou, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhilai
authors.affiliation: Department of Cardiology, Liwan Hospital, Guangzhou Medical University, China. Electronic address: 13312959@qq.com.
authors.forename: Mo
authors.initials: M
authors.lastname: Biling
authors.affiliation: Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye road, 510282 Guangzhou, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Sujun
authors.affiliation: Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye road, 510282 Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chao
authors.affiliation: Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye road, 510282 Guangzhou, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Benchao
authors.affiliation: Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye road, 510282 Guangzhou, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Shuai
authors.affiliation: Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye road, 510282 Guangzhou, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shun
authors.affiliation: Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye road, 510282 Guangzhou, China. Electronic address: zzlspine@foxmail.com.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Hui
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration; D011897:Random Allocation; D051381:Rats; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*
keywords: Mesenchymal stem cells; Physioxic; Spinal cord injury; Transplantation; Umbilical cord