Facilitatory effects of artificial nerve filled with adipose-derived stem cell sheets on peripheral nerve regeneration: An experimental study

Nakajima, Tadahiro; Tada, Kazuhiro; Nakada, Mika; Matsuta, Masashi; Tsuchiya, Hiroyuki

doi:10.1016/j.jos.2020.09.014

Cited by 10 publications

(10 citation statements)

References 28 publications

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“…We successfully isolated primary ADSCs, identified the surface antigens using flow cytometry, and confirmed their adipogenic and osteogenic abilities through direction-induced differentiation. ADSCs promote the repair of PNIs; however, it has been reported that a paracrine mechanism is involved in MSC-mediated tissue repair, whereas direct differentiation of stem cells is weak [ 24 , 25 ]. Considering the limitations of stem cell applications and the fact that the paracrine function of stem cells can be mediated by exosomes, the use of exosomes to replace stem cells for direct treatment has become a feasible alternative method.…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Adipose Mesenchymal Stem Cells Carrying miRNA-22-3p Promote Schwann Cells Proliferation and Migration through Downregulation of PTEN

Yang

Wang

et al. 2022

Disease Markers

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Peripheral nerve injury (PNI) is often resulting from trauma, which leads to severe and permanently disability. Schwann cells are critical for facilitating the regeneration process after PNI. Adipose-derived mesenchymal stem cells (ADSCs) exosomes have been used as a novel treatment for peripheral nerve injury. However, the underlying mechanism remains unclear. In this study, we isolated ADSCs and extracted exosomes, which were verified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot (WB). Cocultured with Dorsal Root Ganglion (DRG) and Schwann cells (SCs) to evaluate the effect of exosomes on the growth of DRG axons by immunofluorescence, and the proliferation and migration of SCs by CCK8 and Transwell assays, respectively. Through exosomal miRNA sequencing and bioinformatic analysis, the related miRNAs and target gene were predicted and identified by dual luciferase assay. Related miRNAs were overexpressed and inhibited, respectively, to clarify their effects; the downstream pathway through the target gene was determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and WB. Results found that ADSC-exosomes could promote the proliferation and migration of SCs and the growth of DRG axons, respectively. Exosomal miRNA-22-3p from ADSCs directly inhibited the expression of Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN), activated phosphorylation of the AKT/mTOR axis, and enhanced SCs proliferation and migration. In conclusion, our findings suggest that ADSC-exosomes could promote SCs function through exosomal miRNA-22-3p, which could be used as a therapeutic target for peripheral nerve injury.

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Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Adipose Mesenchymal Stem Cells Carrying miRNA-22-3p Promote Schwann Cells Proliferation and Migration through Downregulation of PTEN

Yang

Wang

et al. 2022

Disease Markers

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“…Tumor-bearing nerve grafts from the bilateral sciatic nerves were obtained from three rats. Regarding our sample size, we sought to identify differences in this study in conjunction with previous work [44]. A post hoc analysis was performed using G*Power 3.1.9.7 software (Heinrich-Heine University Dusseldorf) to assess the statistical power in order to obtain differences in electrophysiologic evaluation (latency) in Experiment 1 among the autograft, frozen autograft, and resection groups at each week: 0.92 at 4 weeks, 0.99 at 12 weeks, 0.97 at 24 weeks, and 0.89 at 48 weeks, with an a of 0.05.…”

Section: Sample Sizementioning

confidence: 99%

“…An immunohistologic evaluation was performed to assess the number of migrating Schwann cells and axonal regeneration [43,44]. The number of migrating Schwann cells was assessed based on the S100-positive areas (the S100-positive area was calculated using immunohistochemical staining for the S100 protein, which is produced solely and uniformly by Schwann cells associated with axons).…”

Section: Immunohistologic Evaluation Of the Implanted Nervesmentioning

confidence: 99%

Do Liquid Nitrogen–treated Tumor-bearing Nerve Grafts Have the Capacity to Regenerate, and Do They Pose a Risk of Local Recurrence? A Study in Rats

Yonezawa¹,

Yamamoto²,

Hayashi³

et al. 2022

Clin Orthop Relat Res

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Background Under most circumstances, the resection of soft tissue sarcomas of the extremities can be limb-sparing, function-preserving oncologic resections with adequate margins. However, en bloc resection may require resection of the major peripheral nerves, causing poor function in the extremities. Although liquid nitrogenThe institution of one of the authors (HY) has received, during the study period, funding from JSPS KAKENHI under Grant Number JP20K18025. Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

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“…The International Society for Cell Therapy (ISCT) and the International Federation of Fat Therapy and Science (IFATS) have specified three minimum standards for the definition of ASCs: 1) cells must be plastic adherent; 2) they must express CD73, CD90, and CD105, but not CD14, CD11b, CD45, CD19, CD79, and HLA-DR; 3) they must have the potential to differentiate into preadipocytes, chondrocytes, and osteoblasts ( Palumbo et al, 2018 ). According to the properties of different cells obtained, we can use targeted detection methods and establish corresponding animal models, such as 3-(4,5)-dimethylthiazole(-z-y1)-3,5-diphenyltriazolam (MTT) assay and wound model establishment for fibroblasts ( Zhou et al, 2019 ), as well as functional assessment of re-innervation for peripheral nerve regeneration ( Zhou et al, 2020 ; Nakajima et al, 2021 ). However, the standard definition of harvesting and processing technology has not yet been established.…”

Section: The Preparation Of Ascsmentioning

confidence: 99%

Current applications of adipose-derived mesenchymal stem cells in bone repair and regeneration: A review of cell experiments, animal models, and clinical trials

Zhang

Yang

Cao

et al. 2022

Front. Bioeng. Biotechnol.

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In the field of orthopaedics, bone defects caused by severe trauma, infection, tumor resection, and skeletal abnormalities are very common. However, due to the lengthy and painful process of related surgery, people intend to shorten the recovery period and reduce the risk of rejection; as a result, more attention is being paid to bone regeneration with mesenchymal stromal cells, one of which is the adipose-derived mesenchymal stem cells (ASCs) from adipose tissue. After continuous subculture and cryopreservation, ASCs still have the potential for multidirectional differentiation. They can be implanted in the human body to promote bone repair after induction in vitro, solve the problems of scarce sources and large damage, and are expected to be used in the treatment of bone defects and non-union fractures. However, the diversity of its differentiation lineage and the lack of bone formation potential limit its current applications in bone disease. Here, we concluded the current applications of ASCs in bone repair, especially with the combination and use of physical and biological methods. ASCs alone have been proved to contribute to the repair of bone damage in vivo and in vitro. Attaching to bone scaffolds or adding bioactive molecules can enhance the formation of the bone matrix. Moreover, we further evaluated the efficiency of ASC-committed differentiation in the bone in conditions of cell experiments, animal models, and clinical trials. The results show that ASCs in combination with synthetic bone grafts and biomaterials may affect the regeneration, augmentation, and vascularization of bone defects on bone healing. The specific conclusion of different materials applied with ASCs may vary. It has been confirmed to benefit osteogenesis by regulating osteogenic signaling pathways and gene transduction. Exosomes secreted by ASCs also play an important role in osteogenesis. This review will illustrate the understanding of scientists and clinicians of the enormous promise of ASCs’ current applications and future development in bone repair and regeneration, and provide an incentive for superior employment of such strategies.

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Facilitatory effects of artificial nerve filled with adipose-derived stem cell sheets on peripheral nerve regeneration: An experimental study

Cited by 10 publications

References 28 publications

Exosomes Derived from Adipose Mesenchymal Stem Cells Carrying miRNA-22-3p Promote Schwann Cells Proliferation and Migration through Downregulation of PTEN

Exosomes Derived from Adipose Mesenchymal Stem Cells Carrying miRNA-22-3p Promote Schwann Cells Proliferation and Migration through Downregulation of PTEN

Do Liquid Nitrogen–treated Tumor-bearing Nerve Grafts Have the Capacity to Regenerate, and Do They Pose a Risk of Local Recurrence? A Study in Rats

Current applications of adipose-derived mesenchymal stem cells in bone repair and regeneration: A review of cell experiments, animal models, and clinical trials

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