Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis

Cao, Yong; Yan, Xu; Chen, Chun-Yuan; Xie, Hui; Lü, Hongbin; Hu, Jianzhong

doi:10.21203/rs.3.rs-38209/v2

Cited by 5 publications

(4 citation statements)

References 32 publications

(41 reference statements)

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“…1,2 Angiogenesis is an important factor that facilitates neuronal regeneration after SCI. 3 In previous studies, biomaterials, [4][5][6] stem cells, 7 exosomes from neural stem cells, 8,9 or extracorporeal shock waves 10 were used to enhance vessel formation and were found to result in functional recovery in in vivo SCI models.…”

Section: Introductionmentioning

confidence: 99%

Self-assembling peptide gels promote angiogenesis and functional recovery after spinal cord injury in rats

et al. 2022

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Spinal cord injury (SCI) leads to disruption of the blood–spinal cord barrier, hemorrhage, and tissue edema, which impair blood circulation and induce ischemia. Angiogenesis after SCI is an important step in the repair of damaged tissues, and the extent of angiogenesis strongly correlates with the neural regeneration. Various biomaterials have been developed to promote angiogenesis signaling pathways, and angiogenic self-assembling peptides are useful for producing diverse supramolecular structures with tunable functionality. RADA16 (Ac-RARADADARARADADA-NH2), which forms nanofiber networks under physiological conditions, is a self-assembling peptide that can provide mechanical support for tissue regeneration and reportedly has diverse roles in wound healing. In this study, we applied an injectable form of RADA16 with or without the neuropeptide substance P to the contused spinal cords of rats and examined angiogenesis within the damaged spinal cord and subsequent functional improvement. Histological and immunohistochemical analyses revealed that the inflammatory cell population in the lesion cavity was decreased, the vessel number and density around the damaged spinal cord were increased, and the levels of neurofilaments within the lesion cavity were increased in SCI rats that received RADA16 and RADA16 with substance P (rats in the RADA16/SP group). Moreover, real-time PCR analysis of damaged spinal cord tissues showed that IL-10 expression was increased and that locomotor function (as assessed by the Basso, Beattie, and Bresnahan (BBB) scale and the horizontal ladder test) was significantly improved in the RADA16/SP group compared to the control group. Our findings indicate that RADA16 modified with substance P effectively stimulates angiogenesis within the damaged spinal cord and is a candidate agent for promoting functional recovery post-SCI.

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Section: Introductionmentioning

confidence: 99%

Self-assembling peptide gels promote angiogenesis and functional recovery after spinal cord injury in rats

et al. 2022

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“…Recent studies have attributed the repair potential of MSCs to exosomes secreted by these cells (31). So far, several studies have been performed on the use of exosomes in the regeneration of damaged spinal cord tissue in animal models including bone marrow (32)(33)(34)(35)(36)(37), adipose(38), Wharton Jelly(38), human umbilical cords (39,40), neural (41), pricytes (42), Peripheral Macrophage (43), Human urine (44), Microglia (45), and human umbilical venous endothelial cells(46). Studies have shown the unique neuro regenerative, angiogenic, and antioxidant properties of hPMSCs, which are promising applications for the treatment of SCI (47).…”

Section: Discussionmentioning

confidence: 99%

Human placental mesenchymal stem cells derived exosomes improved functional recovery via attenuating apoptosis and increasing axonal regeneration after severe spinal cord injury

Soleimani

Pedram

Saadinam

et al. 2022

Preprint

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Background Spinal cord injury (SCI) due to lack of restoration of damaged axons is associated with sensorimotor impairment. This study was focused on using the human Placental mesenchymal stem cells- exosome (hPMSCs- exosomes) in an animal model of severe SCI under a new myelogram protocol to confirm lumbar puncture (LP) injection accuracy and evaluate intrathecal space. Methods Mesenchymal stem cells (MSC) were extracted from human placenta tissue and were characterized. HPMSCs- exosomes were isolated by ultracentrifuge. After creating the severe SCI model, LP injection of exosomes was performed in the acute phase. Myelogram was also employed. The improved functional recovery of the animals in the treatment and control groups was followed by recording movement scores for 6 weeks. Hematoxylin-Eosin (H&E) staining was used to evaluate to detect pathological changes and glial scar size. The Immunohistochemistry (IHC) of GFAP and NF200 factors as well as the apoptosis tunnel test was investigated in the tissue samples from the injury site Results The results demonstrated that the use of the myelogram can be a feasible, appropriate and cost-effective method to confirm the accuracy of therapeutic agents LP injection and examine the subarachnoid space in the model of laboratory animals. Furthermore, intrathecal injection of hPMSCs-exosomes in the acute phase of SCI can improve motor function by attenuating apoptosis of neurons at the site of injury, decreased GFAP expression and increased NF200 in the treatment group, reducing glial scarring, and increasing axonal regeneration. Improving functional recovery by not creating bedsores in the treatment group and preventing hematuria were other effects of the exosome Conclusions In conclusion, the effects of hPMSCs-exosome can be considered to be not only in restoring function but also in preventing complications and managing symptoms. Thus, the neuroregenerative and anti-apoptotic potential of hPMSCs-exosome can be considered a therapeutic approach in SCI reconstructive medicine.

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“…The ingested exosomes can activate the protein kinase A (PKA) signaling path and promote VEGF expression and consequently angiogenesis (Rauch et al, 2009). Human urine stem cell-derived exosomes can pass through the BSCB and transport ANGPTL3 protein to the SCI area, stimulating angiogenesis through the PI3K/AKT signaling pathway, thereby enabling SCI recovery (Cao et al, 2021). MSC-exosomes packed with phosphatase and tensin homologous small interfering RNA (ExoPTEN) can significantly enhance the angiogenesis and axon regeneration in the damaged spinal cord by reducing PTEN expression in the damaged spinal cord area while reducing microglia and astrocyte proliferation, thereby significantly improving the functional recovery of SCI rats (Kim et al, 2018).…”

Section: Exosomes and Exosomal Mirnasmentioning

confidence: 99%

Emerging Exosomes and Exosomal MiRNAs in Spinal Cord Injury

Feng

Zhang

Zhu

et al. 2021

Front. Cell Dev. Biol.

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Acute spinal cord injury (SCI) is a serious traumatic event to the spinal cord with considerable morbidity and mortality. This injury leads to short- and long-term variations in the spinal cord, and can have a serious effect on the patient’s sensory, motor, or autonomic functions. Due to the complicated pathological process of SCI, there is currently no successful clinical treatment strategy. Exosomes, extracellular vesicles (EVs) with a double-layer membrane structure of 30–150 nm diameter, have recently been considered as critical mediators for communication between cells and tissues by transferring proteins, lipids, and nucleic acids. Further studies verified that exosomes participate in the pathophysiological process of several diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases, and could have a significant impact in their treatment. As natural carriers of biologically active cargos, exosomes have emerged as pathological mediators of SCI. In this review article, we critically discuss the functions of exosomes as intracellular mediators and potential treatments in SCI and provide an outlook on future research.

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Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis

Cited by 5 publications

References 32 publications

Self-assembling peptide gels promote angiogenesis and functional recovery after spinal cord injury in rats

Self-assembling peptide gels promote angiogenesis and functional recovery after spinal cord injury in rats

Human placental mesenchymal stem cells derived exosomes improved functional recovery via attenuating apoptosis and increasing axonal regeneration after severe spinal cord injury

Emerging Exosomes and Exosomal MiRNAs in Spinal Cord Injury

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