DTI metrics can be used as biomarkers to determine the therapeutic effect of stem cells in acute peripheral nerve injury

Chen, Yueyao; Zhang, Xiang; Lin, Xuling; Zhang, Fang; Duan, Xiaohui; Zheng, Chushan; Chen, Meiwei; Wang, Dong-Ye; Zeng, Weike; Shen, Jun

doi:10.1002/jmri.25395

Cited by 25 publications

(48 citation statements)

References 26 publications

(36 reference statements)

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“…Subgroups B and E received only subepineurial microinjections of 5 × 10 5 GFP‐MSCs 1 week postoperatively. Subgroups C and F received only microinjection of the same volume of PBS 18,31 . All subepineurial microinjections were made at the site of the lesion epicenter using a Hamilton 32G needle connected to a 10‐μL syringe (Hamilton Co, Reno, Nevada) after surgical exposure of the sciatic nerve and monitored using a stereomicroscope to ensure the subepineurial position of injection, as described elsewhere 18,31 .…”

Section: Methodsmentioning

confidence: 99%

“…Subgroups C and F received only microinjection of the same volume of PBS 18,31 . All subepineurial microinjections were made at the site of the lesion epicenter using a Hamilton 32G needle connected to a 10‐μL syringe (Hamilton Co, Reno, Nevada) after surgical exposure of the sciatic nerve and monitored using a stereomicroscope to ensure the subepineurial position of injection, as described elsewhere 18,31 . Animals in the first group (subgroups A, B, and C) underwent MRI and sciatic nerve functional assessment at presurgery and 2, 4, 6, and 8 weeks postoperatively.…”

Section: Methodsmentioning

confidence: 99%

“…DTT was initiated from a manually selected ROI, from which tracking lines were propagated bidirectionally according to the principal eigenvector in each voxel. The ROI was placed on a b = 0 image at a site 6 mm proximal to the transection site, and the direction of the diffusion anisotropy was followed until the tracking was terminated at a voxel, depending on the threshold selected―for example, an FA threshold of 0.4, an angular deviation threshold of 30°, and a minimum fiber length threshold of 10 mm, as described elsewhere 2,18,29 . The ROIs were set at 1 mm 2 .…”

Section: Methodsmentioning

confidence: 99%

“…The distal stumps of the injured nerve were removed, fixed in 4% paraformaldehyde for 1 hour, and then preserved in a graded sucrose solution. Axial semithin sections, which were 1 μm thick, were made from the tissue samples of three animals, cut at the distal site from 5 mm to the lesion epicenter and stained with toluidine blue, as described elsewhere 13,18 . Contiguous, longitudinal, 10‐μm sections were made from the tissue samples of another three animals, cut in the entire distal stumps of injured nerves for multiple immunofluorescence staining for CD68 (to detect macrophage infiltration), TLR4, and small proline‐rich protein 1A (SPRR1A) (to detect axonal regeneration), as described elsewhere 13 …”

Section: Methodsmentioning

confidence: 99%

“…Among various types of stem cells, mesenchymal stem cells (MSCs) have been used widely as tissue‐engineering seed cells to repair nerve injury in preclinical research 16,17 . MSCs can promote nerve regeneration after transplantation 1,18–20 . Unfortunately, the survival of transplanted MSCs is jeopardized by the unfavorable immune microenvironment of injured nerves, which substantially hampers the beneficial effect of MSCs on nerve repair 21–24 .…”

Section: Introductionmentioning

confidence: 99%

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Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis

et al. 2020

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Introduction:The immuno-microenvironment of injured nerves adversely affects mesenchymal stem cell (MSC) therapy for neurotmesis. Magnetic resonance imaging (MRI) can be used noninvasively to monitor nerve degeneration and regeneration. The aim of this study was to investigate nerve repair after MSC transplantation combined with microenvironment immunomodulation in neurotmesis by using multiparametric MRI.Methods: Rats with sciatic nerve transection and surgical coaptation were treated with MSCs combined with immunomodulation or MSCs alone. Serial multiparametric MRI examinations were performed over an 8-week period after surgery.Results: Nerves treated with MSCs combined with immunomodulation showed better functional recovery, rapid recovery of nerve T2, fractional anisotropy and radial diffusivity values, and more rapid restoration of the fiber tracks than nerves treated with MSCs alone.Discussion: Transplantation of MSCs in combination with immunomodulation can exert a synergistic repair effect on neurotmesis, which can be monitored by multiparametric MRI. K E Y W O R D Simmunomodulation, magnetic resonance imaging, mesenchymal stem cells, peripheral nerve injuries, tacrolimus, toll-like receptors Abbreviations: AD, axial diffusivity; BDNF, brain-derived neurotrophic factor; DTI, diffusion tensor imaging; DTT, diffusion tensor tractography; ELISA, enzyme-linked immunosorbent assay; FA, fractional anisotropy; FKBP, FK-binding protein; GDNF, glial cell-derived neurotrophic factor; GFP, green fluorescent protein; LPS, lipopolysaccharide; MD, mean diffusivity; MRI, magnetic resonance imaging; MSC, mesenchymal stem cell; PBS, phosphate-buffered saline; RD, radial diffusivity; SD, Sprague-Dawley; SFI, sciatic nerve function index; SPRR1A, small proline-rich protein 1A; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor-α.Zehong Yang and Chushan Zheng contributed equally to this work.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis

et al. 2020

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A Dual‐Modal Magnetic Resonance/Photoacoustic Imaging Tracer for Long‐Term High‐Precision Tracking and Facilitating Repair of Peripheral Nerve Injuries

Ren

Tang

Wang

et al. 2022

Adv Healthcare Materials

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Neuroanatomical tracing is considered a crucial technique to assess the axonal regeneration level after injury, but traditional tracers do not meet the needs of in vivo neural tracing in deep tissues. Magnetic resonance (MR) and photoacoustic (PA) imaging have high spatial resolution, great penetration depth, and rich contrast. Fe 3 O 4 nanoparticles may work well as a dual-modal diagnosis probe for neural tracers, with the potential to improve nerve regeneration. The present study combines antegrade neural tracing imaging therapy for the peripheral nervous system. Fe 3 O 4 @COOH nanoparticles are successfully conjugated with biotinylated dextran amine (BDA) to produce antegrade nano-neural tracers, which are encapsulated by microfluidic droplets to control leakage and allow sustained, slow release. They have many notable advantages over traditional tracers, including dual-modal real-time MR/PA imaging in vivo, long-duration release effect, and limitation of uncontrolled leakage. These multifunctional anterograde neural tracers have potential neurotherapeutic function, are reliable and may be used as a new platform for peripheral nerve injury imaging and treatment integration.

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Assessment of the synergic effect of immunomodulation on nerve repair using multiparametric magnetic resonance imaging

et al. 2017

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Introduction: The immune system plays a pivotal role in nerve injury. The aim of this study was to determine the role of multiparametric magnetic resonance imaging (MRI) in evaluation of the synergic effect of immunomodulation on nerve regeneration in neurotmesis. Methods: Rats with sciatic nerve neurotmesis and surgical repair underwent serial multiparametric MR examinations over an 8-week period after subepineurial microinjection of lipopolysaccharide (LPS) and subsequent subcutaneous injection of FK506 or subepineurial microinjection of LPS or phosphate-buffered saline (PBS) alone. Results: Nerves treated with immunomodulation showed more prominent regeneration than those treated with LPS or PBS alone and more rapid restoration toward normal T2, fractional anisotropy (FA), and radial diffusivity (RD) values than nerves injected with LPS or PBS. Discussion: Nerves treated with immunomodulation exert synergic beneficial effects on nerve regeneration that can be predicted by T2 measurements and FA and RD values.

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DTI metrics can be used as biomarkers to determine the therapeutic effect of stem cells in acute peripheral nerve injury

Abstract: 2 J. Magn. Reson. Imaging 2017;45:855-862.

Cited by 25 publications

References 26 publications

Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis

Magnetic resonance imaging of enhanced nerve repair with mesenchymal stem cells combined with microenvironment immunomodulation in neurotmesis

A Dual‐Modal Magnetic Resonance/Photoacoustic Imaging Tracer for Long‐Term High‐Precision Tracking and Facilitating Repair of Peripheral Nerve Injuries

Assessment of the synergic effect of immunomodulation on nerve repair using multiparametric magnetic resonance imaging

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