In vivo repair of rat transected sciatic nerve by low-intensity pulsed ultrasound and induced pluripotent stem cells-derived neural crest stem cells

Lv, Yonggang; Nan, Panpan; Chen, Guobao; Sha, Yongqiang; Xia, Bin; Yang, Li

doi:10.1007/s10529-015-1939-5

Cited by 48 publications

(49 citation statements)

References 15 publications

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“…LIPUS has been shown to have a positive effect on stem cell proliferation. [30][31][32] Three types of mesenchymal stem cells were treated with 1-MHz LIPUS (ET = 5 or 20 minutes, I SATA = 250 or 750 mW/cm 2 ). All MSCs showed different degrees of proliferation.…”

Section: Discussionmentioning

confidence: 99%

Low‐intensity pulsed ultrasound promotes the proliferation of human bone mesenchymal stem cells by activating PI3K/AKt signaling pathways

Xie

Jiang

Wang

et al. 2019

J of Cellular Biochemistry

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Low‐intensity pulsed ultrasound (LIPUS) is a promising therapy that is widely used in clinical applications and fundamental research. Previous research has shown that LIPUS exposure has a positive effect on stem cell proliferation. However, the impact of LIPUS exposure on human bone marrow mesenchymal stem cells (hBMSCs) remains unknown. In our study, the effect and mechanism of LIPUS exposure on the proliferation of hBMSCs were investigated, and the optimal parameters of LIPUS were determined. hBMSCs were obtained and identified by flow cytometry, and the proliferation of hBMSCs was measured using the Cell Counting Kit‐8 assay to determine cell cycle and cell count. Expression levels of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKt) pathway proteins and cyclin D1 were determined by western blot analysis. Next, hBMSCs were successfully cultured and identified as multipotent mesenchymal stem cells. We found that LIPUS could promote the proliferation of hBMSCs when the exposure time was 5 or 10 minutes per day. Furthermore, 50 or 60 mW/cm2 LIPUS had a more significant effect on cell proliferation, but if cells were irradiated by LIPUS for 20 minutes once a day, an intensity of at least 50 mW/cm2 could markedly inhibit cell growth. Cell cycle analysis demonstrated that LIPUS treatment drives cells to enter S and G2/M phases from the G0/G1 phase. LIPUS exposure increased phosphorylation of PI3K/AKt and significantly upregulated expression of cyclin D1. However, these effects were inhibited when cells were treated with PI3K inhibitor (LY294002), which in turn reduced LIPUS‐mediated proliferation of hBMSCs. These results suggest that LIPUS exposure may be involved in the proliferation of hBMSCs via activation of the PI3K/AKt signaling pathway and high expression of cyclin D1, and the intensity of 50 or 60 mW/cm2 and exposure time of 5 minutes were determined to be the optimal parameters for LIPUS exposure.

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Section: Discussionmentioning

confidence: 99%

Low‐intensity pulsed ultrasound promotes the proliferation of human bone mesenchymal stem cells by activating PI3K/AKt signaling pathways

Xie

Jiang

Wang

et al. 2019

J of Cellular Biochemistry

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“…LIPUS treatment was performed on tissue culture plate or the incision site of the rat, following the procedure previously described (Lv et al, ; Xia et al, ). In brief, LIPUS was generated by a LIPUS apparatus US10 (Cosmogamma, Italy) and transmitted through the bottom of the culture dish or the incision site of the rat via coupling gel (Tianjin Xiyuansi Workshop, China) coated between ultrasonic transducer and dish or the rat skin.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous studies found that low‐intensity ultrasound (LIPUS) with intensity of 500 mW/cm 2 could promote the proliferation of induced pluripotent stem cells‐derived neural crest stem cells (iPSCs‐NCSCs), enhance the cell viability, and promote iPSCs‐NCSCs differentiation into neurons and Schwann cells (Lv, Zhao, Chen, Sha, & Yang, ). In vivo studies also found that LIPUS combined with iPSCs‐NCSCs treatment can improve the repair of sciatic nerve with 10‐mm injury in rat (Lv et al, ). However, the molecular mechanisms involved in the proliferation and differentiation of iPSCs‐NCSCs after LIPUS treatment are still unclear.…”

Section: Introductionmentioning

confidence: 98%

Low‐intensity pulsed ultrasound combination with induced pluripotent stem cells‐derived neural crest stem cells and growth differentiation factor 5 promotes sciatic nerve regeneration and functional recovery

Xia

Chen

Zou

et al. 2019

J Tissue Eng Regen Med

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The treatment of lengthy peripheral nerve defect is challenging in the field of nerve regeneration. Our previous studies have shown that low-intensity pulsed ultrasound (LIPUS) could promote the proliferation, cell viability, and neural differentiation of induced pluripotent stem cells-derived neural crest stem cells (iPSCs-NCSCs) andimprove the regeneration of damaged peripheral nerve. In this study, the mechanical signal transduction pathway of LIPUS promoting iPSCs-NCSCs proliferation and differentiation was further explored, and the effects of LIPUS combined with iPSCs-NCSCs, perfluorotributylamine (PFTBA), and growth differentiation factor 5 (GDF5) on the repair of peripheral nerve injury were evaluated. Results showed LIPUS may regulate the proliferation and differentiation of iPSCs-NCSCs through FAK-ERK1/2 signal pathway. PFTBA could supply sufficient oxygen to promote the viability of iPSCs-NCSCs under 5% hypoxia culture condition and provide a favourable microenvironment for nerve regeneration. The addition of GDF5 could promote the neural differentiation of iPSCs-NCSCs in vitro. LIPUS treatment of allogeneic decellularized nerve conduit containing iPSCs-NCSCs, PFTBA, and GDF5 has very good effect on the repair of sciatic nerve injury. Taken together, these results provide functional evidence that LIPUS might be a useful tool to explore alternative approaches in the field of nerve regeneration. KEYWORDS growth differentiation factor 5, induced pluripotent stem cells, low-intensity pulsed ultrasound, perfluorotributylamine, peripheral nerve regeneration, signal pathway

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“…In addition, it has been exhibited that combined application of low‐intensity pulsed ultrasound with iPSCs–neural crest‐derived stem cells can stimulate the regeneration and reconstruction of rat‐transected sciatic nerve (Lv et al, ). However, some important issues need to be considered in order to use iPSCs in nerve tissue engineering, such as differences among iPSC populations in differentiation and expansion stages and selection of the suitable differentiation phase of the cells for desired tissue engineering applications (Wang et al, ).…”

Section: Transplantation Of Cell‐seeded Nerve Conduits For Peripheralmentioning

confidence: 99%

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

Jahromi

Razavi

Bakhtiari

2019

J Tissue Eng Regen Med

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Peripheral nerve damage is a common clinical complication of traumatic injury occurring after accident, tumorous outgrowth, or surgical side effects. Although the new methods and biomaterials have been improved recently, regeneration of peripheral nerve gaps is still a challenge. These injuries affect the quality of life of the patients negatively. In the recent years, many efforts have been made to develop innovative nerve tissue engineering approaches aiming to improve peripheral nerve treatment following nerve injuries. Herein, we will not only outline what we know about the peripheral nerve regeneration but also offer our insight regarding the types of nerve conduits, their fabrication process, and factors associated with conduits as well as types of animal and nerve models for evaluating conduit function. Finally, nerve regeneration in a rat sciatic nerve injury model by nerve conduits has been considered, and the main aspects that may affect the preclinical outcome have been discussed.

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In vivo repair of rat transected sciatic nerve by low-intensity pulsed ultrasound and induced pluripotent stem cells-derived neural crest stem cells

Abstract: Combination of LIPUS with iPSCs-NCSCs promoted the regeneration and reconstruction of rat transected sciatic nerve and is an efficient and cost-effective method for peripheral nerve regeneration.

Cited by 48 publications

References 15 publications

Low‐intensity pulsed ultrasound promotes the proliferation of human bone mesenchymal stem cells by activating PI3K/AKt signaling pathways

Low‐intensity pulsed ultrasound promotes the proliferation of human bone mesenchymal stem cells by activating PI3K/AKt signaling pathways

Low‐intensity pulsed ultrasound combination with induced pluripotent stem cells‐derived neural crest stem cells and growth differentiation factor 5 promotes sciatic nerve regeneration and functional recovery

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

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