Transplantation of expanded endothelial colony-forming cells improved outcomes of traumatic brain injury in a mouse model

Zhang, Yongqiang; Li, Ying; Wang, Shaobo; Han, Zhaoxia; Huang, Xintao; Li, Shenghui; Chen, Fanglian; Niu, Rong⁃dong; Dong, Jing; Jiang, Rongcai; Zhang, Jianning

doi:10.1016/j.jss.2013.05.073

Cited by 43 publications

(40 citation statements)

References 42 publications

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“…Due to the higher cell frequency (20) and the stronger cell proliferative ability (19,21), human UCB has been defined as a more ideal source of EPCs. UCB-EPCs have been a focus of regenerative treatment for ischemic diseases, and a number of studies have examined their application in ischemic diseases in various animal models; however, some researchers have used EPCs at ununiformed passages, such as passage 2–5 (37), passage 3–4 (29), passage 5 (38), or in some case, have not stated the specific cell passage used (39,40). Thus, further supportive evidence for cell passage selection in ischemic treatment is still needed.…”

Section: Discussionmentioning

confidence: 99%

Decreased phosphorylation of PDGFR-β impairs the angiogenic potential of expanded endothelial progenitor cells via the inhibition of PI3K/Akt signaling

Mei

Wang

et al. 2017

International Journal of Molecular Medicine

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Abstract.Human umbilical cord blood-derived endothelial progenitor cells (EPCs) have been proven to contribute to postnatal angiogenesis, and have been applied in various models of ischemia. However, to date, to the best of our knowledge, there is no available data on the angiogenic properties of EPCs during the process of in vitro expansion. In this study, we expanded EPCs to obtain cells at different passages, and analyzed their cellular properties and angiogenic ability. In the process of expansion, no changes were observed in cell cobblestone-like morphology, apoptotic rate and telomere length. However, the cell proliferative ability was significantly decreased. Additionally, the expression of CD144, CD90 and KDR was significantly downregulated in the later-passage cells. Vascular formation assay in vitro revealed that EPCs at passage 4 and 6 formed more integrated and organized capillary-like networks. In a murine model of hind limb ischemia, the transplantation of EPCs at passage 4 and 6 more effectively promoted perfusion recovery in the limbs on days 7 and 14, and promoted limb salvage and histological recovery. Furthermore, the phosphorylation levels of platelet-derived growth factor receptor-β (PDGFR-β) were found to be significantly decreased with the in vitro expansion process, accompanied by the decreased activation of the PI3K/Akt signaling pathway. When PDGFR inhibitor was used to treat the EPCs, the differences in the angiogenic potential and migratory ability among the EPCs at different passages were no longer observed; no significant differences were also observed in the levels of phosphorylated PI3K/Akt between the EPCs at different passages following treatment with the inhibitor. On the whole, our findings indicate that the levels of phosphorylated PDGFR-β are decreased in EPCs with the in vitro expansion process, which impairs their angiogenic potential by inhibiting PI3K/Akt signaling. Our findings may aid in the more effective selection of EPCs of different passages for the clinical therapy of ischemic disease.

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Section: Discussionmentioning

confidence: 99%

Decreased phosphorylation of PDGFR-β impairs the angiogenic potential of expanded endothelial progenitor cells via the inhibition of PI3K/Akt signaling

Mei

Wang

et al. 2017

International Journal of Molecular Medicine

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“…A 2.0-mm hole was drilled on the right parietal skull (2.0 mm posterior from bregma and 1.5 mm lateral to the sagittal suture) to expose the dura. Mice were subjected to experimental FPI (model 01-B; New Sun Health Products, Cedar Bluff, VA) injury of severity of 2.0 atm, as described previously (Dixon et al, 1987;McIntosh et al, 1989 Q2 ; Guo et al, 2009;Zhang et al, 2013). In brief, a female Leur-Lok fitting was cemented to the craniotomy site (MODEL 01-B, New Sun, USA).…”

Section: Animals and Tbi Modelmentioning

confidence: 99%

VEGI attenuates the inflammatory injury and disruption of blood–brain barrier partly by suppressing the TLR4/NF-κB signaling pathway in experimental traumatic brain injury

Gao

Zhao

et al. 2015

Brain Research

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“…Electrical stimulation further increased the number of EPCs in the peripheral blood. Our previous study confirmed that these cells could home to injured brain tissue and promote angiogenesis (Zhang et al., 2013). …”

Section: Discussionmentioning

confidence: 99%

“…In addition, researchers have reported that ES promotes functional recovery and brain remodeling by enhancing angiogenesis in a rat model of ischemia (Cheng et al., 2012). Similarly, angiogenesis plays an important role in neurological recovery after TBI (Cheng et al., 2012; Huang et al., 2013; Zhang et al., 2013). However, to date, limited studies have investigated the effects of ES treatment on TBI.…”

Section: Introductionmentioning

confidence: 99%

Electrical stimulation improved cognitive deficits associated with traumatic brain injury in rats

Zheng

Dong

et al. 2017

Brain and Behavior

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IntroductionCognitive deficits associated with traumatic brain injury (TBI) reduce patient quality of life. However, to date, there have been no effective treatments for TBI‐associated cognitive deficits. In this study, we aimed to determine whether electrical stimulation (ES) improves cognitive deficits in TBI rats.MethodsRats were randomly divided into three groups: the Sham control group, electrical stimulation group (ES group), and No electrical stimulation control group (N‐ES group). Following fluid percussion injury, the rats in the ES group received ES treatment for 3 weeks. Potent cognitive function‐relevant factors, including the escape latency, time percentage in the goal quadrant, and numbers of CD34+ cells, von Willebrand Factor+ (vWF +) vessels, and circulating endothelial progenitor cells (EPCs), were subsequently assessed using the Morris water maze (MWM) test, immunohistochemical staining, and flow cytometry.ResultsCompared with the rats in the N‐ES group, the rats in the ES group exhibited a shorter escape latency on day 3 (p = .025), day 4 (p = .011), and day 5 (p = .003), as well as a higher time percentage in the goal quadrant (p = .025) in the MWM test. After 3 weeks of ES, there were increased numbers of CD34+ cells (p = .008) and vWF + vessels (p = .000) in the hippocampus of injured brain tissue in the ES group compared with those in the N‐ES group. Moreover, ES also significantly increased the number of EPCs in the peripheral blood from days 3 to 21 after TBI in the ES group (p < .05).ConclusionsTaken together, these findings suggest that ES may improve cognitive deficits induced by TBI, and this protective effect may be a result, in part, of enhanced angiogenesis, which may be attributed to the increased mobilization of EPCs in peripheral blood.

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Transplantation of expanded endothelial colony-forming cells improved outcomes of traumatic brain injury in a mouse model

Cited by 43 publications

References 42 publications

Decreased phosphorylation of PDGFR-β impairs the angiogenic potential of expanded endothelial progenitor cells via the inhibition of PI3K/Akt signaling

Decreased phosphorylation of PDGFR-β impairs the angiogenic potential of expanded endothelial progenitor cells via the inhibition of PI3K/Akt signaling

VEGI attenuates the inflammatory injury and disruption of blood–brain barrier partly by suppressing the TLR4/NF-κB signaling pathway in experimental traumatic brain injury

Electrical stimulation improved cognitive deficits associated with traumatic brain injury in rats

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