Yong Cao1,2,3, Yan Xu2,3,4, Chunyuan Chen5, Hui Xie6, Hongbin Lu2,3,4, Jianzhong Hu7,8,9. 1. Department of Spine Surgery and Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China. 2. Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China. 3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. 4. Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China. 5. Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. 6. Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China. Huixie@csu.edu.cn. 7. Department of Spine Surgery and Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China. jianzhonghu@hotmail.com. 8. Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China. jianzhonghu@hotmail.com. 9. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. jianzhonghu@hotmail.com.
Abstract
BACKGROUND: Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate if the effect of an administered injection of exosomes derived from human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism. METHODS: Exosomes were isolated from USC and identified by transmission electron microscopy (TEM) and Western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model were assessed. RESULTS: In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood-brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in USC-Exo and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway. CONCLUSION: Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.
BACKGROUND:Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate if the effect of an administered injection of exosomes derived from human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism. METHODS: Exosomes were isolated from USC and identified by transmission electron microscopy (TEM) and Western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model were assessed. RESULTS: In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood-brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in USC-Exo and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway. CONCLUSION: Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.
Entities:
Keywords:
Angiogenesis; Angiopoietin-like protein 3; Exosome; Human urine stem cell; Spinal cord injury
Authors: Fabiana Quagliarini; Yan Wang; Julia Kozlitina; Nick V Grishin; Rhonda Hyde; Eric Boerwinkle; David M Valenzuela; Andrew J Murphy; Jonathan C Cohen; Helen H Hobbs Journal: Proc Natl Acad Sci U S A Date: 2012-11-12 Impact factor: 11.205
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