The effect of mesenchymal stem cells and surgical angiogenesis on immune response and revascularization of acellular nerve allografts in a rat sciatic defect model

Bedar, Meiwand; Saffari, Tiam M.; Johnson, Aaron J.; Shin, Alexander Y.

doi:10.1016/j.bjps.2022.02.076

Cited by 6 publications

(6 citation statements)

References 48 publications

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“…However, histological features of the regenerated nerves in the ANA + cells group were similar to those in the autograft group (P > 0.05), except for signi cant difference in the myelin thickness (P < 0.05). These results indicated that when repairing long-distance facial nerve defects in rats, the neural functional and morphological recovery in the ANA laden with EPI-NCSCs group were superior to cell-free acellular scaffolds [32,44,45].…”

Section: Discussionmentioning

confidence: 85%

Application of second near infrared fluorescence imaging to trace CelTrac1000-labeled hair follicle epidermal neural crest stem cells in repairing rat facial nerve defects

Lv,

Zhu,

Zhang

et al. 2023

Preprint

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Background Tissue engineering based on stem cells has achieved satisfactory results in repairing facial nerve defects. However, the in vivo process of the transplanted cells has not been fully clear until now, although it is critical to understand the process and the underlying mechanism of regeneration for better therapeutic outcomes. Recently, second near-infrared window (NIR-II) fluorescence imaging has emerged as a rapidly evolving bio-imaging technique capable of visualizing and quantifying biological processes at the cellular level of living organisms. Methods Firstly, rat hair follicle epidermal neural crest stem cells (EPI-NCSCs) were isolated, cultured and identified by expression of SOX10 and Nestin, and then labeled with CelTrac1000. Rat acellular nerve allografts (ANAs) were prepared by chemical extraction. Secondly, 30 adult male rats were randomly and equally assigned into three groups: ANA + cells group, ANA group, and autograft group. The buccal branch of the facial nerve on right side was exposed and a 10-mm-long gap was bridged by ANA laden with CelTrac1000-labeled EPI-NCSCs, ANA laden with CelTrac1000 dye, and autologous nerve, respectively. Thirdly, CelTrac1000-labeled EPI-NCSCs were detected by NIR-II optical imaging system to visualize the behavior of the transplanted cells in vivo postoperatively. Finally, vibrissa movement, compound muscle action potentials (CMAPs) of vibrissal muscle, facial motoneurons retrotraced by Fluorogold, morphology and histology of the regenerated nerves in three groups were analyzed after surgery, respectively. Results Through 14 weeks of dynamic observation, we found that EPI-NCSCs successfully survived in the ANAs in vivo. Meanwhile, the region of the NIR-II fluorescence signals was gradually limited to be consistent with the route of the regenerative segment of the facial nerve. Furthermore, the degree of the vibrissa movement, the recovery value of the onset latency and amplitude of CMAPs, the number of Fluorogold-labeled cells, the CD31 positive area/total area, the mean gray value of S100 and β-tubulin III, the number and the diameter of the myelinated nerve fibers in the ANA group were lower than the other two groups (P < 0.05), and the other two groups had similar values (P > 0.05). Additionally, the thickness of the myelin sheaths was the thinnest in the ANA group, and the thickest in the autograft group (P< 0.05). Conclusions The migration map of local CelTrac1000-labeled EPI-NCSCs was successfully monitored by the NIR-II fluorescence imaging system when EPI-NCSCs within the ANAs were applied to treat rat facial nerve defects. Additionally, EPI-NCSCs promoted the ANAs to repair facial nerve defects in a small animal model.

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Section: Discussionmentioning

confidence: 85%

Application of second near infrared fluorescence imaging to trace CelTrac1000-labeled hair follicle epidermal neural crest stem cells in repairing rat facial nerve defects

Lv,

Zhu,

Zhang

et al. 2023

Preprint

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“…Nerve autografts obtain blood supply differently than ANAs or TENCs since they have preexisting capillary networks within themselves that longitudinally inosculate with vasculature in the proximal nerve stump (Liu et al, 2022; Saffari et al, 2021). Additionally, when the autograft metabolic requirements exceed the supply by inosculated vessels, for instance in longer nerve autografts, centripetal angiogenesis (new vessel formation) occurs from the surrounding wound bed (Bedar et al, 2022). Hirasawa et al showed that neural microvascular regeneration of a nerve graft occurs in two forms: the extrinsic form that occurs in 3–6 weeks after transplantation and involves longitudinal surface blood vessels and the intrinsic form that can occur over 24 weeks and involves plexiform blood vessels (Hirasawa et al, 1974).…”

Section: Nerve Graft Revascularizationmentioning

confidence: 99%

“…However, ADSC differentiation or vascular density was not measured in this study. In a rodent sciatic nerve injury model, one team supplemented their ANA with undifferentiated ADSCs and found that this group had the highest vascular volume (Bedar et al, 2022). Another team studied angiogenesis in a 10 mm rat sciatic nerve transection model and found that ANA seeded with ADSCs had the highest vascular surface area and demonstrated a centripetal vascular pattern, compared to the longitudinal inosculation pattern in the autograft nerve repair group (Mathot et al, 2020).…”

Section: Stem Cellsmentioning

confidence: 99%

Bioengineering approaches for nerve graft revascularization: Current concepts and future directions

Pereira

Lazar

Wang

2023

WIREs Mechanisms of Disease

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Peripheral nerve injury (PNI) is the most common neurological injury in civilian and military injuries, with over 360,000 PNI procedures performed in the US yearly. Segmental loss of nerve tissue results in a nerve gap precluding a tension-free primary repair, and in these cases, interpositional autologous or acellular nerve allografts are used to bridge the gap. Graft ischemia time is a critical factor in achieving satisfactory nerve regeneration. Rapid nerve graft revascularization is essential in order to sustain Schwann cell growth which in turn is crucial for axonal regeneration. Currently, nerve autografts are considered the gold standard for segmental nerve gaps but are associated with several disadvan-

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“…MSCs were isolated from the inguinal fat pad of Lewis rats and previously characterized based on multipotency and expression of MSC markers. 33 Cells were expended in Advanced Minimum Essential Medium (Thermo Fisher Scientific) supplemented with 5% platelet lysate (PLTMax; Mill Creek Life Sciences), 1% penicillin/streptomycin (Penicillin-Streptomycin 10,000 U/mL; Thermo Fisher Scientific), 1% GlutaMAX (GlutaMAX supplement 100X; Thermo Fisher Scientific), and 0.2% heparin (heparin sodium injection, 1000 USP units/mL; Fresenius Kabi). Passage 3 MSCs were used for in vivo experimentation.…”

Section: Msc Culturementioning

confidence: 99%

Dynamic Seeding versus Microinjection of Adipose-Derived Mesenchymal Stem Cells to Acellular Nerve Allograft Reconstructions

Bedar

Pulos

Shin

2023

Plastic &Amp; Reconstructive Surgery

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Background: Functional recovery following acellular nerve allograft (ANA) reconstructions remains inferior to autologous nerve grafting, but have demonstrated improved outcomes with the addition of adipose-derived mesenchymal stem cells (MSC). Controversy exists regarding the optimal cell delivery method to enhance ANA reconstructions. We investigated the functional recovery of ANAs after dynamic seeding versus microinjection of MSCs. Methods: Forty Lewis rats underwent reconstruction of a 10-mm sciatic nerve defect. Animals were divided into four groups: reversed autograft, ANA alone, ANA dynamically seeded, or ANA injected with MSCs. During the survival period, ultrasound measurements of the tibialis anterior (TA) muscle cross-sectional area were performed. At 12 weeks, functional recovery was evaluated using measurements of ankle contracture, compound muscle action potential (CMAP), maximum isometric tetanic force (ITF), muscle mass, histomorphometry, and immunofluorescence. Results: The dynamic seeding and microinjection groups demonstrated higher cross-sectional TA muscle area recovery than autografts and ANAs alone at week 8 and week 4 and 8, respectively. The ankle contracture and CMAP amplitude recovery were superior in autografts and both seeding methods compared to ANAs alone. The microinjection group demonstrated significantly higher ITF, muscle mass, and number of axons compared to ANAs alone. Both seeding methods showed higher CD34 densities compared to ANAs alone. No significant differences between dynamic seeding and microinjection were observed for both functional and histological outcomes. Conclusions: The addition of MSCs to ANAs demonstrated earlier motor regeneration compared to autografts and ANAs alone. Both seeding methods improved functional outcomes in the rat sciatic nerve defect model. Clinical Relevance Statement: Future clinical applications of stem cell-based nerve reconstructions are dependent on determining optimum delivery methods, which are technically feasible, reproducible, cost-efficient, and timely.

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The effect of mesenchymal stem cells and surgical angiogenesis on immune response and revascularization of acellular nerve allografts in a rat sciatic defect model

Cited by 6 publications

References 48 publications

Application of second near infrared fluorescence imaging to trace CelTrac1000-labeled hair follicle epidermal neural crest stem cells in repairing rat facial nerve defects

Application of second near infrared fluorescence imaging to trace CelTrac1000-labeled hair follicle epidermal neural crest stem cells in repairing rat facial nerve defects

Bioengineering approaches for nerve graft revascularization: Current concepts and future directions

Dynamic Seeding versus Microinjection of Adipose-Derived Mesenchymal Stem Cells to Acellular Nerve Allograft Reconstructions

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