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Marin A, Herlea V, Bancu A, Giuglea C, Țăpoi DA, Ciongariu AM, Marin GG, Marinescu SA, Dobrete NA, Dumitru AV, Trambitaș C, Șerban D, Sajin M. Correlation Between the Clinical and Histopathological Results in Experimental Sciatic Nerve Defect Surgery. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:317. [PMID: 40005434 PMCID: PMC11857492 DOI: 10.3390/medicina61020317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/07/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025]
Abstract
Background and Objectives: Peripheral nerve defect regeneration is subject to ongoing research regarding the use of conduits associated with various cells or molecules. This article aims to correlate histopathological and clinical outcomes at the end of a 12-week experiment performed on a rat sciatic nerve model and show which repair method has the best results. Materials and Methods: Forty male Wistar rats were divided into four groups to compare the results of four different methods of reconstruction for sciatic nerve defect: (1) nerve graft-control group, (2) empty aortic conduit, (3) aortic conduit filled with platelet-rich plasma (PRP) and (4) aortic conduit filled with mesenchymal stem cells. There were three clinical examinations: a sensitivity test, a mobility test and a footprint test. After 12 weeks, the nerves were excised and assessed microscopically using conventional Hematoxylin and Eosin staining (HE), special stains and immunohistochemistry (IHC). Results: Nerve regeneration was observed in all batches, both from the clinical and histopathological assessment; the two types of examinations correlated for each batch. Immunohistochemistry and special staining offered a more complete image of the nerve regeneration results. Conclusions: Superior nerve regeneration was achieved using an aortic conduit in combination with either PRP or stem cells, while the empty aortic conduit recorded lesser results.
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Affiliation(s)
- Andrei Marin
- Plastic Surgery Department, St. John’s Hospital, Carol Davila University, 042122 Bucharest, Romania; (A.M.); (C.G.)
| | - Vlad Herlea
- Pathology Department, “Fundeni” Hospital, Carol Davila University, Fundeni Street, 258, 022328 Bucharest, Romania
| | - Alice Bancu
- Pathology Department, Sante Clinic, 060754 Bucharest, Romania;
| | - Carmen Giuglea
- Plastic Surgery Department, St. John’s Hospital, Carol Davila University, 042122 Bucharest, Romania; (A.M.); (C.G.)
| | - Dana Antonia Țăpoi
- Pathology Department, University Emergency Hospital, Carol Davila University, 050474 Bucharest, Romania; (D.A.Ț.); (A.M.C.); (A.V.D.); (M.S.)
| | - Ana Maria Ciongariu
- Pathology Department, University Emergency Hospital, Carol Davila University, 050474 Bucharest, Romania; (D.A.Ț.); (A.M.C.); (A.V.D.); (M.S.)
| | | | | | | | - Adrian Vasile Dumitru
- Pathology Department, University Emergency Hospital, Carol Davila University, 050474 Bucharest, Romania; (D.A.Ț.); (A.M.C.); (A.V.D.); (M.S.)
| | - Cristian Trambitaș
- Plastic Surgery Department, G. E. Palade University of Medicine, Pharmacy, Science and Technology from Târgu Mureș, 540142 Târgu Mureș, Romania;
| | - Dragoș Șerban
- Surgery Department, University Emergency Hospital, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Maria Sajin
- Pathology Department, University Emergency Hospital, Carol Davila University, 050474 Bucharest, Romania; (D.A.Ț.); (A.M.C.); (A.V.D.); (M.S.)
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Liu Y, Zhang X, Xiao C, Liu B. Engineered hydrogels for peripheral nerve repair. Mater Today Bio 2023; 20:100668. [PMID: 37273791 PMCID: PMC10232914 DOI: 10.1016/j.mtbio.2023.100668] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 05/06/2023] [Accepted: 05/16/2023] [Indexed: 06/06/2023] Open
Abstract
Peripheral nerve injury (PNI) is a complex disease that often appears in young adults. It is characterized by a high incidence, limited treatment options, and poor clinical outcomes. This disease not only causes dysfunction and psychological disorders in patients but also brings a heavy burden to the society. Currently, autologous nerve grafting is the gold standard in clinical treatment, but complications, such as the limited source of donor tissue and scar tissue formation, often further limit the therapeutic effect. Recently, a growing number of studies have used tissue-engineered materials to create a natural microenvironment similar to the nervous system and thus promote the regeneration of neural tissue and the recovery of impaired neural function with promising results. Hydrogels are often used as materials for the culture and differentiation of neurogenic cells due to their unique physical and chemical properties. Hydrogels can provide three-dimensional hydration networks that can be integrated into a variety of sizes and shapes to suit the morphology of neural tissues. In this review, we discuss the recent advances of engineered hydrogels for peripheral nerve repair and analyze the role of several different therapeutic strategies of hydrogels in PNI through the application characteristics of hydrogels in nerve tissue engineering (NTE). Furthermore, the prospects and challenges of the application of hydrogels in the treatment of PNI are also discussed.
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Affiliation(s)
- Yao Liu
- Hand and Foot Surgery Department, First Hospital of Jilin University, Xinmin Street, Changchun, 130061, PR China
| | - Xiaonong Zhang
- Key Laboratory of Polymer Ecomaterials, Jilin Biomedical Polymers Engineering Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China
| | - Chunsheng Xiao
- Key Laboratory of Polymer Ecomaterials, Jilin Biomedical Polymers Engineering Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China
| | - Bin Liu
- Hand and Foot Surgery Department, First Hospital of Jilin University, Xinmin Street, Changchun, 130061, PR China
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Benefit of Adjuvant Mesenchymal Stem Cell Transplantation to Critical-Sized Peripheral Nerve Defect Repair: A Systematic Review and Meta-Analysis of Preclinical Studies. J Clin Med 2023; 12:jcm12041306. [PMID: 36835844 PMCID: PMC9966712 DOI: 10.3390/jcm12041306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 01/29/2023] [Accepted: 01/31/2023] [Indexed: 02/10/2023] Open
Abstract
Critically sized nerve defects cause devastating life-long disabilities and require interposition for reconstruction. Additional local application of mesenchymal stem cells (MSCs) is considered promising to enhance peripheral nerve regeneration. To better understand the role of MSCs in peripheral nerve reconstruction, we performed a systematic review and meta-analysis of the effects of MSCs on critically sized segment nerve defects in preclinical studies. 5146 articles were screened following PRISMA guidelines using PubMed and Web of Science. A total of 27 preclinical studies (n = 722 rats) were included in the meta-analysis. The mean difference or the standardized mean difference with 95% confidence intervals for motor function, conduction velocity, and histomorphological parameters of nerve regeneration, as well as the degree of muscle atrophy, was compared in rats with critically sized defects and autologous nerve reconstruction treated with or without MSCs. The co-transplantation of MSCs increased the sciatic functional index (3.93, 95% CI 2.62 to 5.24, p < 0.00001) and nerve conduction velocity recovery (1.49, 95% CI 1.13 to 1.84, p = 0.009), decreased the atrophy of targeted muscles (gastrocnemius: 0.63, 95% CI 0.29 to 0.97 p = 0.004; triceps surae: 0.08, 95% CI 0.06 to 0.10 p = 0.71), and promoted the regeneration of injured axons (axon number: 1.10, 95% CI 0.78 to 1.42, p < 0.00001; myelin sheath thickness: 0.15, 95% CI 0.12 to 0.17, p = 0.28). Reconstruction of critically sized peripheral nerve defects is often hindered by impaired postoperative regeneration, especially in defects that require an autologous nerve graft. This meta-analysis indicates that additional application of MSC can enhance postoperative peripheral nerve regeneration in rats. Based on the promising results in vivo experiments, further studies are needed to demonstrate potential clinical benefits.
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Siemionow M, Strojny MM, Kozlowska K, Brodowska S, Grau-Kazmierczak W, Cwykiel J. Application of Human Epineural Conduit Supported with Human Mesenchymal Stem Cells as a Novel Therapy for Enhancement of Nerve Gap Regeneration. Stem Cell Rev Rep 2021; 18:642-659. [PMID: 34787795 PMCID: PMC8930890 DOI: 10.1007/s12015-021-10301-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/07/2021] [Indexed: 12/18/2022]
Abstract
Various therapeutic methods have been suggested to enhance nerve regeneration. In this study, we propose a novel approach for enhancement of nerve gap regeneration by applying human epineural conduit (hEC) supported with human mesenchymal stem cells (hMSC), as an alternative to autograft repair. Restoration of 20 mm sciatic nerve defect with hEC created from human sciatic nerve supported with hMSC was tested in 4 experimental groups (n = 6 each) in the athymic nude rat model (Crl:NIH-Foxn1rnu): 1 - No repair control, 2 - Autograft control, 3 - Matched diameter hEC filled with 1 mL saline, 4 - Matched diameter hEC supported with 3 × 106 hMSC. Assessments included: functional tests: toe-spread and pinprick, regeneration assessment by immunofluorescence staining: HLA-1, HLA-DR, NGF, GFAP, Laminin B, S-100, VEGF, vWF and PKH26 labeling; histomorphometric analysis of myelin thickness, axonal density, fiber diameter and myelinated nerve fibers percentage; Gastrocnemius Muscle Index (GMI) and muscle fiber area ratio. Best sensory and motor function recovery, as well as GMI and muscle fiber area ratio, were observed in the autograft group, and were comparable to the hEC with hMSC group (p = 0.038). Significant improvements of myelin thickness (p = 0.003), fiber diameter (p = 0.0296), and percentage of myelinated fibers (p < 0.0001) were detected in hEC group supported with hMSC compared to hEC with saline controls. At 12-weeks after nerve gap repair, hEC combined with hMSC revealed increased expression of neurotrophic and proangiogenic factors, which corresponded with improvement of function comparable with the autograft control. Application of our novel hEC supported with hMSC provides a potential alternative to the autograft nerve repair.
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Affiliation(s)
- Maria Siemionow
- Poznan University of Medical Sciences, Poznan, Poland. .,Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, USA.
| | - Marcin Michal Strojny
- Poznan University of Medical Sciences, Poznan, Poland.,Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, USA
| | - Katarzyna Kozlowska
- Poznan University of Medical Sciences, Poznan, Poland.,Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, USA
| | - Sonia Brodowska
- Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, USA
| | | | - Joanna Cwykiel
- Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL, USA
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Bademoğlu G, Erdal N, Uzun C, Taşdelen B. The effects of pulsed electromagnetic field on experimentally induced sciatic nerve injury in rats. Electromagn Biol Med 2021; 40:408-419. [PMID: 33797305 DOI: 10.1080/15368378.2021.1907403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Some experimental research indicates that low-frequency pulsed electromagnetic field (PEMF) stimulation may accelerate regeneration in sciatic nerve injury. However, little research has examined the electrophysiological and functional properties of regenerating peripheral nerves under PEMF. The main aim of the present study is to investigate the effects of PEMF on sciatic nerve regeneration in short- and long-term processes with electrophysiologically and functionally after crushing damage. Crush lesions were performed using jewelery forceps for 30 s. After crush injury of the sciatic nerves, 24 female Wistar-Albino rats were divided into 3 groups with 8 rats in each group: SH(Sham), SNI (Sciatic Nerve Injury), SNI+PEMF(Sciatic Nerve Injury+Pulsed Electromagnetic Field). SNI+PEMF group was exposed to PEMF (4 h/day, intensity; 0.3mT, low-frequency; 2 Hz) for 40-days. Electrophysiological records (at the beginning and 1st, 2nd, 4th and 6th weeks post-crush) and functional footprints (at 1st, 2nd, 3rd, 4th, 5th and 6th weeks post crush) were measured from all groups during the experiment. The results were compared to SNI and SNI+PEMF groups, it was found that amplitude and area parameters in the first-week were significantly higher and latency was lower in the SNI+PEMF group than in the SNI group (p < 0,05). However, the effect of PEMF was not significant in the 2nd, 4th, 6th weeks. In addition, in the 1st and 2nd weeks, the SSI parameters were significantly higher in SNI+PMF group than SNI group (p < .05). These results indicate that low-frequency PEMF is not effective for long-periods of application time while PEMF may be useful during the short-term recovery period.
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Affiliation(s)
- Gülten Bademoğlu
- Department of Biophysics, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Nurten Erdal
- Department of Biophysics, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Coşar Uzun
- Department of Biophysics, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Bahar Taşdelen
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Mersin University, Mersin, Türkiye
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Wang YH, Wang DR, Guo YC, Liu JY, Pan J. The application of bone marrow mesenchymal stem cells and biomaterials in skeletal muscle regeneration. Regen Ther 2020; 15:285-294. [PMID: 33426231 PMCID: PMC7770413 DOI: 10.1016/j.reth.2020.11.002] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 11/07/2020] [Accepted: 11/16/2020] [Indexed: 02/08/2023] Open
Abstract
Skeletal muscle injuries have bothered doctors and caused great burdens to the public medical insurance system for a long time. Once injured, skeletal muscles usually go through the processes of inflammation, repairing and remodeling. If repairing and remodeling stages are out of balance, scars will be formed to replace injured skeletal muscles. At present, clinicians usually use conventional methods to restore the injured skeletal muscles, such as flap transplantation. However, flap transplantation sometimes needs to sacrifice healthy autologous tissues and will bring extra harm to patients. In recent years, stem cells-based tissue engineering provides us new treatment ideas for skeletal muscle injuries. Stem cells are cells with multiple differentiation potential and have ability to differentiate into adult cells under special condition. Skeletal muscle tissues also have stem cells, called satellite cells, but they are in small amount and new muscle fibers that derived from them may not be enough to replace injured fibers. Bone marrow mesenchymal stem cells (BM-MSCs) could promote musculoskeletal tissue regeneration and activate the myogenic differentiation of satellite cells. Biomaterial is another important factor to promote tissue regeneration and greatly enhance physiological activities of stem cells in vivo. The combined use of stem cells and biomaterials will gradually become a mainstream to restore injured skeletal muscles in the future. This review article mainly focuses on the review of research about the application of BM-MSCs and several major biomaterials in skeletal muscle regeneration over the past decades.
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Key Words
- 3D-ECM, three dimensional extracellular matrix
- ASCs, adipose stem cells
- BDNF, brain derived neurotrophic factor
- BM-MSCs
- BM-MSCs, bone marrow mesenchymal stem cells
- Biomaterial
- CREB, cAMP- response element binding protein
- DPSCs, dental pulp stem cells
- Differentiation
- ECM, extracellular matrix
- ECs, endothelial cells
- EGF, epidermal growth factor
- FGF, fibroblast growth factor
- FGF-2, fibroblast growth factor-2
- GCSF, granulocyte colony-stimulating factor
- GDNF, glial derived neurotrophic factor
- GPT, gelatin-poly(ethylene glycol)- tyramine
- HGF, hepatocyte growth factor
- IGF-1, insulin-like growth factor-1
- IL, interleukin
- LIF, leukemia inhibitory factor
- MRF, myogenic muscle factor
- NSAIDs, non-steroidal drugs
- PDGF-BB, platelet derived growth factor-BB
- PGE2, prostaglandin E2
- PRP, platelet rich plasma
- S1P, sphingosine 1-phosphate
- SDF-1, stromal cell derived factor-1
- Skeletal muscle injury
- TGF-β, transforming growth factor-β
- Tissue regeneration
- TrkB, tyrosine kinaseB
- VEGF, vascular endothelial growth factor
- VML, volumetric muscle loss
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Affiliation(s)
- Yu-Hao Wang
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.,National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, PR China
| | - Dian-Ri Wang
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.,National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, PR China
| | - Yu-Chen Guo
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.,National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China
| | - Ji-Yuan Liu
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.,National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China
| | - Jian Pan
- State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.,National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.,National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, PR China
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Zhang Q, Wu P, Chen F, Zhao Y, Li Y, He X, Huselstein C, Ye Q, Tong Z, Chen Y. Brain Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor-Transfected Bone Mesenchymal Stem Cells for the Repair of Periphery Nerve Injury. Front Bioeng Biotechnol 2020; 8:874. [PMID: 32850732 PMCID: PMC7406647 DOI: 10.3389/fbioe.2020.00874] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 07/08/2020] [Indexed: 12/17/2022] Open
Abstract
Peripheral nerve injury is a common clinical neurological disease. In our previous study, highly oriented poly (L-lactic acid) (PLLA)/soy protein isolate (SPI) nanofiber nerve conduits were constructed and exhibited a certain repair capacity for peripheral nerve injury. In order to further improve their nerve repairing efficiency, the bone mesenchymal stem cells (BMSCs) overexpressing brain derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were introduced into the conduits as seed cells and then were used to repair the 10-mm sciatic nerve defects in rats. The nerve repair efficiency of the functional nerve conduits was evaluated by gait experiment, electrophysiological test, and a series of assays such as hemotoxylin-eosin (HE) staining, immunofluorescence staining, toluidine blue (TB) staining, transmission electron microscopy (TEM) observation of regenerated nerve and Masson's trichrome staining of gastrocnemius muscle. The results showed that the conduits containing BMSCs overexpressing BDNF and GDNF double-factors group had better nerve repairing efficiency than blank BMSCs and single BDNF or GDNF factor groups, and superior to autografts group in some aspects. These data demonstrated that BDNF and GDNF produced by BMSCs could synergistically promote peripheral nerve repair. This study shed a new light on the conduits and stem cells-based peripheral nerve repair.
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Affiliation(s)
- Qiang Zhang
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, School of Basic Medical Sciences, Wuhan University, Wuhan, China
- Hangzhou Singclean Medical Products Co., Ltd., Hangzhou, China
| | - Ping Wu
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Feixiang Chen
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Yanan Zhao
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Yinping Li
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Xiaohua He
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Céline Huselstein
- CNRS UMR 7561 and FR CNRS-INSERM 32.09, Nancy University, Vandæuvre-lès-Nancy, France
| | - Qifa Ye
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Wuhan, China
- Hubei Engineering Center of Natural Polymers-Based Medical Materials, Wuhan University, Wuhan, China
| | - Zan Tong
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Yun Chen
- Department of Biomedical Engineering and Hubei Province Key Laboratory of Allergy and Immune Related Diseases, School of Basic Medical Sciences, Wuhan University, Wuhan, China
- Hubei Engineering Center of Natural Polymers-Based Medical Materials, Wuhan University, Wuhan, China
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Kubiak CA, Grochmal J, Kung TA, Cederna PS, Midha R, Kemp SWP. Stem-cell-based therapies to enhance peripheral nerve regeneration. Muscle Nerve 2019; 61:449-459. [PMID: 31725911 DOI: 10.1002/mus.26760] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 10/31/2019] [Accepted: 11/12/2019] [Indexed: 12/13/2022]
Abstract
Peripheral nerve injury remains a major cause of morbidity in trauma patients. Despite advances in microsurgical techniques and improved understanding of nerve regeneration, obtaining satisfactory outcomes after peripheral nerve injury remains a difficult clinical problem. There is a growing body of evidence in preclinical animal studies demonstrating the supportive role of stem cells in peripheral nerve regeneration after injury. The characteristics of both mesoderm-derived and ectoderm-derived stem cell types and their role in peripheral nerve regeneration are discussed, specifically focusing on the presentation of both foundational laboratory studies and translational applications. The current state of clinical translation is presented, with an emphasis on both ethical considerations of using stems cells in humans and current governmental regulatory policies. Current advancements in cell-based therapies represent a promising future with regard to supporting nerve regeneration and achieving significant functional recovery after debilitating nerve injuries.
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Affiliation(s)
- Carrie A Kubiak
- Department of Surgery, Section of Plastic and Reconstructive Surgery, University of Michigan, Ann Arbor, Michigan
| | - Joey Grochmal
- Department of Clinical Neurosciences and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Theodore A Kung
- Department of Surgery, Section of Plastic and Reconstructive Surgery, University of Michigan, Ann Arbor, Michigan
| | - Paul S Cederna
- Department of Surgery, Section of Plastic and Reconstructive Surgery, University of Michigan, Ann Arbor, Michigan.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Rajiv Midha
- Department of Clinical Neurosciences and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Stephen W P Kemp
- Department of Surgery, Section of Plastic and Reconstructive Surgery, University of Michigan, Ann Arbor, Michigan.,Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
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The Use and Delivery of Stem Cells in Nerve Regeneration: Preclinical Evidence and Regulatory Considerations. Ann Plast Surg 2019; 80:448-456. [PMID: 29166311 DOI: 10.1097/sap.0000000000001259] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Outcomes following peripheral nerve injury remain poor despite the regenerative capacity displayed by the peripheral nervous system. Current therapies are limited and do not provide satisfactory functional recovery in a multitude of cases. Biomaterials have decreased the need for nerve autograft across small nerve gaps in small-caliber nerves, but the lack of a cellular substrate presents a limiting factor to the effectiveness of this therapy. Schwann cells are the supportive cells in the peripheral nervous system and play an integral role in the physiological response and regeneration following nerve injury. Limitations to autologous Schwann cells include donor site morbidity during harvesting, limited expansion capability, and finite source. Stem cells are multipotent or pluripotent cells with self-renewing capabilities that show promise to improve functional recovery following nerve injury. Differentiation of stem cells into supportive Schwann cells could provide additional trophic support without the disadvantages of autologous Schwann cells, providing an avenue to improve existing therapies. A variety of stem cells have been evaluated in animal models for this clinical application; the current options, along with their clinical feasibility, are summarized in this article.
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Yu Z, Xu N, Zhang N, Xiong Y, Wang Z, Liang S, Zhao D, Huang F, Zhang C. Repair of Peripheral Nerve Sensory Impairments via the Transplantation of Bone Marrow Neural Tissue-Committed Stem Cell-Derived Sensory Neurons. Cell Mol Neurobiol 2019; 39:341-353. [PMID: 30684112 PMCID: PMC11469867 DOI: 10.1007/s10571-019-00650-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 01/04/2019] [Indexed: 01/20/2023]
Abstract
The present study aimed to investigate the efficacy of transplantation of bone marrow neural tissue-committed stem cell-derived sensory neuron-like cells for the repair of peripheral nerve sensory impairments in rats. Bone marrow was isolated and cultured to obtain the neural tissue-committed stem cells (NTCSCs), and the differentiation of these cells into sensory neuron-like cells was induced. Bone marrow mesenchymal stem cells (BMSCs), bone marrow NTCSCs, and bone marrow NTCSC-derived sensory neurons (NTCSC-SNs) were transplanted by microinjection into the L4 and L5 dorsal root ganglions (DRGs) in an animal model of sensory defect. On the 2nd, 4th, 8th, and 12th week after the transplantation, the effects of the three types of stem cells on the repair of the sensory functional defect were analyzed via behavioral observation, sensory function evaluation, electrophysiological examination of the sciatic nerve, and morphological observation of the DRGs. The results revealed that the transplanted BMSCs, NTCSCs, and NTCSC-SNs were all able to repair the sensory nerves. In addition, the effect of the NTCSC-SNs was significantly better than that of the other two types of stem cells. The general posture and gait of the animals in the sensory defect model exhibited evident improvement over time. Plantar temperature sensitivity and pain sensitivity gradually recovered, and the sensation latency was reduced, with faster sensory nerve conduction velocity. Transplantation of NTCSC-SNs can improve the repair of peripheral nerve sensory defects in rats.
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Affiliation(s)
- Zhenhai Yu
- Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People's Republic of China
- Department of Human Anatomy, College of Basic Medical Sciences, Second Military Medical University, Shanghai, 200433, People's Republic of China
| | - Ning Xu
- Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, People's Republic of China
| | - Naili Zhang
- Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People's Republic of China
| | - Yanlian Xiong
- Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People's Republic of China
| | - Zhiqiang Wang
- Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People's Republic of China
| | - Shaohua Liang
- Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People's Republic of China
| | - Dongmei Zhao
- Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People's Republic of China
| | - Fei Huang
- Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People's Republic of China.
| | - Chuansen Zhang
- Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People's Republic of China.
- Department of Human Anatomy, College of Basic Medical Sciences, Second Military Medical University, Shanghai, 200433, People's Republic of China.
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11
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A Simple Dynamic Strategy to Deliver Stem Cells to Decellularized Nerve Allografts. Plast Reconstr Surg 2019; 142:402-413. [PMID: 29889737 DOI: 10.1097/prs.0000000000004614] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The addition of adipose-derived mesenchymal stromal cells to decellularized nerve allografts may improve outcomes of nerve reconstruction. Prior techniques used for cell seeding are traumatic to both the mesenchymal stromal cells and nerve graft. An adequate, reliable, and validated cell seeding technique is an essential step for evaluating the translational utility of mesenchymal stromal cell-enhanced decellularized nerve grafts. The purpose of this study was to develop a simple seeding strategy with an optimal seeding duration. METHODS A dynamic bioreactor was used to seed rat and human mesenchymal stromal cells separately onto rat and human decellularized nerve allografts. Cell viability was evaluated by MTS assays and cellular topology after seeding was determined by scanning electron microscopy. Cell density and distribution were determined by Live/Dead assays and Hoechst staining at four different time points (6, 12, 24, and 72 hours). The validity and reliability of the seeding method were calculated. RESULTS Cells remained viable at all time points, and mesenchymal stromal cells exhibited exponential growth in the first 12 hours of seeding. Seeding efficiency increased significantly from 79.5 percent at 6 hours to 89.2 percent after 12 hours of seeding (p = 0.004). Both intrarater reliability (r = 0.97) and interrater reliability (r = 0.92) of the technique were high. CONCLUSIONS This study describes and validates a new method of effectively seeding decellularized nerve allografts with mesenchymal stromal cells. This method is reproducible, distributes cells homogenously over the graft, and does not traumatize the intraneural architecture of the allograft. Use of this validated seeding technique will permit critical comparison of graft outcomes.
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12
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Siemionow M, Cwykiel J, Uygur S, Kwiecien G, Oztürk C, Szopinski J, Madajka M. Application of epineural sheath conduit for restoration of 6-cm long nerve defects in a sheep median nerve model. Microsurgery 2018; 39:332-339. [PMID: 30512213 DOI: 10.1002/micr.30393] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 09/12/2018] [Accepted: 10/05/2018] [Indexed: 11/08/2022]
Abstract
BACKGROUND Due to limited number of studies, we tested feasibility of autologous epineural sheath conduit (ESC) in repair of 6-cm median nerve gaps in a sheep-the large animal model. MATERIALS AND METHODS Eight ewes, 6-8 months old, 30-35 kg, were divided into three experimental groups: group 1-no defect repair (n = 4 nerves/group), group 2-autograft controls (n = 6 nerves/group), group 3-autologous ESC filled with saline (n = 6 nerves/group). ESC was constructed from a 6-cm long segment of sheep median nerve and tested for expression of laminin B, Glial fibrillary acidic protein (GFAP), S-100 and CD31 using immunofluorescent staining. At 6 months after nerve repair, nerve conduction velocity and somatosensory evoked potentials (SSEP) assessed neurosensory recovery, while histomorphometry tested nerve regeneration. RESULTS Ex vivo characterization of ESC, before in vivo nerve gap repair, showed high laminin B expression, which supports axonal growth. At 6 months post-repair, structural integrity of ESC was preserved. ESC was well-vascularized and tissue adhesions were comparable to autograft controls. The maximal conduction velocities (29.80 ± 5.85 ms vs. 32.28 ± 6.75 ms; p = .44), action potential amplitudes (32.68 ± 17.44 mV vs. 44.14 ± 23.10 mV; p = .38) and SSEP amplitude values (6.18 ± 5.84 mV vs. 4.68 ± 2.53 mV; p = .28) were comparable between autograft and ESC groups. Presence of regenerating axons was confirmed in the distal segment of ESC at 6 months after repair. CONCLUSION The feasibility of ESC in restoration of 6-cm long nerve defects in a sheep median nerve model was confirmed by nerve conduction assessments and correlated with axonal regeneration tested by histomorphometry. We confirmed ESC potential in support of regeneration of long nerve defects.
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Affiliation(s)
- Maria Siemionow
- Department of Orthopaedics, University of Illinois at Chicago, Chicago, Illinois.,Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Joanna Cwykiel
- Department of Orthopaedics, University of Illinois at Chicago, Chicago, Illinois.,Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Safak Uygur
- Department of Orthopaedics, University of Illinois at Chicago, Chicago, Illinois
| | | | - Can Oztürk
- Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Jacek Szopinski
- Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio.,Department of General Surgery, Hepatobiliary Surgery and Transplant Surgery, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Torun, Poland
| | - Maria Madajka
- Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio
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13
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Sarker M, Naghieh S, McInnes AD, Schreyer DJ, Chen X. Regeneration of peripheral nerves by nerve guidance conduits: Influence of design, biopolymers, cells, growth factors, and physical stimuli. Prog Neurobiol 2018; 171:125-150. [DOI: 10.1016/j.pneurobio.2018.07.002] [Citation(s) in RCA: 108] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 07/24/2018] [Accepted: 07/26/2018] [Indexed: 01/10/2023]
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14
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Park S, Jung N, Myung S, Choi Y, Chung KW, Choi BO, Jung SC. Differentiation of Human Tonsil-Derived Mesenchymal Stem Cells into Schwann-Like Cells Improves Neuromuscular Function in a Mouse Model of Charcot-Marie-Tooth Disease Type 1A. Int J Mol Sci 2018; 19:ijms19082393. [PMID: 30110925 PMCID: PMC6121309 DOI: 10.3390/ijms19082393] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Revised: 08/06/2018] [Accepted: 08/10/2018] [Indexed: 01/18/2023] Open
Abstract
Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited motor and sensory neuropathy, and is caused by duplication of PMP22, alterations of which are a characteristic feature of demyelination. The clinical phenotype of CMT1A is determined by the degree of axonal loss, and patients suffer from progressive muscle weakness and impaired sensation. Therefore, we investigated the potential of Schwann-like cells differentiated from human tonsil-derived stem cells (T-MSCs) for use in neuromuscular regeneration in trembler-J (Tr-J) mice, a model of CMT1A. After differentiation, we confirmed the increased expression of Schwann cell (SC) markers, including glial fibrillary acidic protein (GFAP), nerve growth factor receptor (NGFR), S100 calcium-binding protein B (S100B), glial cell-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), which suggests the differentiation of T-MSCs into SCs (T-MSC-SCs). To test their functional efficiency, the T-MSC-SCs were transplanted into the caudal thigh muscle of Tr-J mice. Recipients’ improved locomotive activity on a rotarod test, and their sciatic function index, which suggests that transplanted T-MSC-SCs ameliorated demyelination and atrophy of nerve and muscle in Tr-J mice. Histological and molecular analyses showed the possibility of in situ remyelination by T-MSC-SCs transplantation. These findings demonstrate that the transplantation of heterologous T-MSC-SCs induced neuromuscular regeneration in mice and suggest they could be useful for the therapeutic treatment of patients with CMT1A disease.
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Affiliation(s)
- Saeyoung Park
- Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07985, Korea.
| | - Namhee Jung
- Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07985, Korea.
| | - Seoha Myung
- Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07985, Korea.
| | - Yoonyoung Choi
- Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07985, Korea.
| | - Ki Wha Chung
- Department of Biological Sciences, Kongju National University, Gongju 32588, Korea.
| | - Byung-Ok Choi
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
| | - Sung-Chul Jung
- Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07985, Korea.
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15
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Uz M, Das SR, Ding S, Sakaguchi DS, Claussen JC, Mallapragada SK. Advances in Controlling Differentiation of Adult Stem Cells for Peripheral Nerve Regeneration. Adv Healthc Mater 2018; 7:e1701046. [PMID: 29656561 DOI: 10.1002/adhm.201701046] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Revised: 01/08/2018] [Indexed: 01/01/2023]
Abstract
Adult stems cells, possessing the ability to grow, migrate, proliferate, and transdifferentiate into various specific phenotypes, constitute a great asset for peripheral nerve regeneration. Adult stem cells' ability to undergo transdifferentiation is sensitive to various cell-to-cell interactions and external stimuli involving interactions with physical, mechanical, and chemical cues within their microenvironment. Various studies have employed different techniques for transdifferentiating adult stem cells from distinct sources into specific lineages (e.g., glial cells and neurons). These techniques include chemical and/or electrical induction as well as cell-to-cell interactions via co-culture along with the use of various 3D conduit/scaffold designs. Such scaffolds consist of unique materials that possess controllable physical/mechanical properties mimicking cells' natural extracellular matrix. However, current limitations regarding non-scalable transdifferentiation protocols, fate commitment of transdifferentiated stem cells, and conduit/scaffold design have required new strategies for effective stem cells transdifferentiation and implantation. In this progress report, a comprehensive review of recent advances in the transdifferentiation of adult stem cells via different approaches along with multifunctional conduit/scaffolds designs is presented for peripheral nerve regeneration. Potential cellular mechanisms and signaling pathways associated with differentiation are also included. The discussion with current challenges in the field and an outlook toward future research directions is concluded.
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Affiliation(s)
- Metin Uz
- Department of Chemical and Biological Engineering Iowa State University Ames IA 50011 USA
| | - Suprem R. Das
- Department of Mechanical Engineering Iowa State University Ames IA 50011 USA
- Division of Materials Science and Engineering Ames Laboratory Ames IA 50011 USA
| | - Shaowei Ding
- Department of Mechanical Engineering Iowa State University Ames IA 50011 USA
| | - Donald S. Sakaguchi
- Neuroscience Program Iowa State University Ames IA 50011 USA
- Department of Genetics Development and Cell Biology Iowa State University Ames IA 50011 USA
| | - Jonathan C. Claussen
- Department of Mechanical Engineering Iowa State University Ames IA 50011 USA
- Division of Materials Science and Engineering Ames Laboratory Ames IA 50011 USA
| | - Surya K. Mallapragada
- Department of Chemical and Biological Engineering Iowa State University Ames IA 50011 USA
- Department of Genetics Development and Cell Biology Iowa State University Ames IA 50011 USA
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16
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Alvites R, Rita Caseiro A, Santos Pedrosa S, Vieira Branquinho M, Ronchi G, Geuna S, Varejão AS, Colette Maurício A. Peripheral nerve injury and axonotmesis: State of the art and recent advances. COGENT MEDICINE 2018. [DOI: 10.1080/2331205x.2018.1466404] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Affiliation(s)
- Rui Alvites
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
| | - Ana Rita Caseiro
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
- Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia, Universidade do Porto (REQUIMTE/LAQV), R. Dr. Roberto Frias, 4200-465 Porto, Portugal
| | - Sílvia Santos Pedrosa
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
| | - Mariana Vieira Branquinho
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
| | - Giulia Ronchi
- Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Stefano Geuna
- Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Artur S.P. Varejão
- CECAV, Centro de Ciência Animal e Veterinária, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801 Vila Real, Portugal
- Department of Clinical and Biological Sciences, and Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Ospedale San Luigi, 10043 Orbassano, Turin, Italy
| | - Ana Colette Maurício
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal
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17
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Wieringa PA, Gonçalves de Pinho AR, Micera S, Wezel RJA, Moroni L. Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies. Adv Healthc Mater 2018; 7:e1701164. [PMID: 29349931 DOI: 10.1002/adhm.201701164] [Citation(s) in RCA: 88] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Revised: 11/13/2017] [Indexed: 12/19/2022]
Abstract
Biofabrication techniques have endeavored to improve the regeneration of the peripheral nervous system (PNS), but nothing has surpassed the performance of current clinical practices. However, these current approaches have intrinsic limitations that compromise patient care. The "gold standard" autograft provides the best outcomes but requires suitable donor material, while implantable hollow nerve guide conduits (NGCs) can only repair small nerve defects. This review places emphasis on approaches that create structural cues within a hollow NGC lumen in order to match or exceed the regenerative performance of the autograft. An overview of the PNS and nerve regeneration is provided. This is followed by an assessment of reported devices, divided into three major categories: isotropic hydrogel fillers, acting as unstructured interluminal support for regenerating nerves; fibrous interluminal fillers, presenting neurites with topographical guidance within the lumen; and patterned interluminal scaffolds, providing 3D support for nerve growth via structures that mimic native PNS tissue. Also presented is a critical framework to evaluate the impact of reported outcomes. While a universal and versatile nerve repair strategy remains elusive, outlined here is a roadmap of past, present, and emerging fabrication techniques to inform and motivate new developments in the field of peripheral nerve regeneration.
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Affiliation(s)
- Paul A. Wieringa
- Department of Complex Tissue RegenerationMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht University Universiteitssingel 40 Maastricht 6229 ER The Netherlands
| | - Ana Rita Gonçalves de Pinho
- Tissue Regeneration DepartmentMIRA InstituteUniversity of Twente Drienerlolaan 5 Enschede 7522 NB The Netherlands
| | - Silvestro Micera
- BioRobotics InstituteScuola Superiore Sant'Anna Viale Rinaldo Piaggio 34 Pontedera 56025 Italy
- Translational Neural Engineering LaboratoryEcole Polytechnique Federale de Lausanne Ch. des Mines 9 Geneva CH‐1202 Switzerland
| | - Richard J. A. Wezel
- BiophysicsDonders Institute for BrainCognition and BehaviourRadboud University Kapittelweg 29 Nijmegen 6525 EN The Netherlands
- Biomedical Signals and SystemsMIRA InstituteUniversity of Twente Drienerlolaan 5 Enschede 7522 NB The Netherlands
| | - Lorenzo Moroni
- Department of Complex Tissue RegenerationMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht University Universiteitssingel 40 Maastricht 6229 ER The Netherlands
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18
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D’Arpa S, Zabbia G, Cannizzaro C, Salimbeni G, Plescia F, Mariolo AV, Cassata G, Cicero L, Puleio R, Martorana A, Moschella F, Cordova A. Seeding nerve sutures with minced nerve-graft (MINE-G): a simple method to improve nerve regeneration in rats. Acta Chir Belg 2018; 118:27-35. [PMID: 28738725 DOI: 10.1080/00015458.2017.1353237] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of this study was to assess the effect of seeding the distal nerve suture with nerve fragments in rats. METHODS On 20 rats, a 15 mm sciatic nerve defect was reconstructed with a nerve autograft. In the Study Group (10 rats), a minced 1 mm nerve segment was seeded around the nerve suture. In the Control Group (10 rats), a nerve graft alone was used. At 4 and 12 weeks, a walking track analysis with open field test (WTA), hystomorphometry (number of myelinated fibers (n), fiber density (FD) and fiber area (FA) and soleus and gastrocnemius muscle weight ratios (MWR) were evaluated. The Student t-test was used for statistical analysis. RESULTS At 4 and 12 weeks the Study Group had a significantly higher n and FD (p = .043 and .033). The SMWR was significantly higher in the Study Group at 12 weeks (p = .0207). CONCLUSIONS Seeding the distal nerve suture with nerve fragments increases the number of myelinated fibers, the FD and the SMWR. The technique seems promising and deserves further investigation to clarify the mechanisms involved and its functional effects.
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Affiliation(s)
- Salvatore D’Arpa
- Plastische Heelkunde, Universitair Ziekenhuis Gent, Gent, Belgium
| | - Giovanni Zabbia
- Division of Plastic and Reconstructive Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Carla Cannizzaro
- Department of Sciences for Health Promotion and Mother and Child Care ‘GIUSEPPE D’ALESSANDRO’, University of Palermo, Palermo, Italy
| | | | - Fulvio Plescia
- Department of Sciences for Health Promotion and Mother and Child Care ‘GIUSEPPE D’ALESSANDRO’, University of Palermo, Palermo, Italy
| | - Alessio Vincenzo Mariolo
- Division of Plastic and Reconstructive Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Giovanni Cassata
- Laboratory Animal House/Unit, Institute of Experimental Zooprophylactic of Sicily, Palermo, Italy
| | - Luca Cicero
- Laboratory Animal House/Unit, Institute of Experimental Zooprophylactic of Sicily, Palermo, Italy
| | - Roberto Puleio
- Histopathology and Immunohistochemistry Laboratory, Institute Experimental Zooprophylactic of Sicily, Palermo, Italy
| | - Anna Martorana
- Department of Human Pathology, University of Palermo, Palermo, Italy
| | - Francesco Moschella
- Division of Plastic and Reconstructive Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
| | - Adriana Cordova
- Division of Plastic and Reconstructive Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
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19
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Chitosan nerve conduits seeded with autologous bone marrow mononuclear cells for 30 mm goat peroneal nerve defect. Sci Rep 2017; 7:44002. [PMID: 28287100 PMCID: PMC5347120 DOI: 10.1038/srep44002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 02/03/2017] [Indexed: 01/01/2023] Open
Abstract
In the current research, to find if the combination of chitosan nerve conduits seeded with autologous bone marrow mononuclear cells (BM-MNCs) can be used to bridge 30 mm long peroneal nerve defects in goats, 15 animals were separated into BM-MNC group (n = 5), vehicle group (n = 5), and autologous nerve graft group (n = 5). 12 months after the surgery, animals were evaluated by behavioral observation, magnetic resonance imaging tests, histomorphological and electrophysiological analysis. Results revealed that animals in BM-MNC group and autologous nerve graft group achieved fine functional recovery; magnetic resonance imaging tests and histomorphometry analysis showed that the nerve defect was bridged by myelinated nerve axons in those animals. No significant difference was found between the two groups concerning myelinated axon density, axon diameter, myelin sheath thickness and peroneal nerve action potential. Animals in vehicle group failed to achieve significant functional recovery. The results indicated that chitosan nerve conduits seeded with autologous bone marrow mononuclear cells have strong potential in bridging long peripheral nerve defects and could be applied in future clinical trials.
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20
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Jiang L, Jones S, Jia X. Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities. Int J Mol Sci 2017; 18:ijms18010094. [PMID: 28067783 PMCID: PMC5297728 DOI: 10.3390/ijms18010094] [Citation(s) in RCA: 147] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 12/26/2016] [Accepted: 12/27/2016] [Indexed: 12/21/2022] Open
Abstract
Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and donor site morbidity. Stem cell transplantation for peripheral nerve regeneration offers an alternative cell-based therapy with several regenerative benefits. Stem cells have the potential to differentiate into Schwann-like cells that recruit macrophages for removal of cellular debris. They also can secrete neurotrophic factors to promote axonal growth, and remyelination. Currently, various types of stem cell sources are being investigated for their application to peripheral nerve regeneration. This review highlights studies involving the stem cell types, the mechanisms of their action, methods of delivery to the injury site, and relevant pre-clinical or clinical data. The purpose of this article is to review the current point of view on the application of stem cell based strategy for peripheral nerve regeneration.
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Affiliation(s)
- Liangfu Jiang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
| | - Salazar Jones
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
| | - Xiaofeng Jia
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
- Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
- Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
- Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
- Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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21
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Nerve regeneration techniques respecting the special characteristics of the inferior alveolar nerve. J Craniomaxillofac Surg 2016; 44:1381-6. [PMID: 27435058 DOI: 10.1016/j.jcms.2016.06.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 05/21/2016] [Accepted: 06/27/2016] [Indexed: 11/21/2022] Open
Abstract
PURPOSE The aim of this study was to examine the in situ regeneration of the inferior alveolar nerve (IAN) in its bony channel, using autologous tissue in combination with a recombinant human nerve growth factor (rhNGF). MATERIALS AND METHODS A total of 20 New Zealand rabbits were randomly divided into five groups. Following dissection of the IAN, the animals underwent reconstruction either with muscle tissue (groups 1 and 2) or with fat tissue (groups 3 and 4). In group 5 (control), the dissected nerve was resected and reconstructed by placement of the reversed autologous segment. After 2 and 4 weeks, 1 mL rhNGF was locally injected in groups 1 and 3. Nerve function was monitored by measuring the jaw-opening reflex using electromyography for a period of 24 weeks. RESULTS Regeneration of the nerve was achieved in all groups, but preoperative threshold values were not achieved. Comparing the experimental groups to the control, there was a significant difference in favor of the autologous nerve reconstruction. Differences between the experimental groups remained statistically not significant. CONCLUSION Regeneration of the IAN with autologous tissue is possible, but without achieving preoperative thresholds. Additional injection of a growth factor seems to improve the speed of regeneration for fat and muscle grafts.
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22
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Bobkiewicz A, Cwykiel J, Siemionow M. Anatomic variations of brachial and lumbosacral plexus models in different rat strains. Microsurgery 2016; 37:327-333. [PMID: 27270490 DOI: 10.1002/micr.30078] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 04/28/2016] [Accepted: 05/13/2016] [Indexed: 12/18/2022]
Abstract
PURPOSE Selection of an appropriate model for preclinical assessment of new methods of peripheral nerve injury management is crucial. This report presents anatomic variations within brachial and lumbosacral plexuses in three selected rat strains Sprague Dawley (Hsd:Sprague Dawley SD), Lewis (LEW/SsNHsd), and Athymic Nude (Hsd:RH-Foxn1rnu ) rats. METHODS Based on their strain eighteen rats were divided into three groups. A total of 90 brachial plexus nerves (axillary, musculocutaneous, median, ulnar, and radial nerves) and 72 lumbosacral plexus nerves (sciatic, tibial, common peroneal, and sural nerves) were analyzed for the length, diameter and correlation with the body weight. A detailed anatomic course of each nerve within the brachial and lumbosacral plexuses was outlined. RESULTS The sural nerve was the longest nerve in all studied rat strains, whereas the sciatic nerve had the largest diameter. Comparison of all the nerves' length demonstrated that the Lewis rat sciatic and sural nerves were significantly shorter (P < 0.05). No significant differences in nerve diameters were found among the analyzed rat strain groups. Significant correlation was revealed between the length of sciatic nerve and the rats' weight, which is irrelevant to the rats' genetic background. CONCLUSIONS This study confirmed that nerves' length within rat's brachial and lumbosacral plexus depends on the inter-individual variations within the rat strains rather than on the differences in the peripheral nerve development, which is inherent to the specific rat strain. Correlation between the nerve length and body weight, suggests that bigger rats should be considered for studies requiring access to the long nerves. © 2016 Wiley Periodicals, Inc. Microsurgery 37:327-333, 2017.
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Affiliation(s)
- Adam Bobkiewicz
- Department of General Surgery, Gastroenterological Oncology and Endocrine Surgery, Poznan University of Medical Sciences, Poznan, Poland
| | - Joanna Cwykiel
- Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL
| | - Maria Siemionow
- Department of Orthopaedics, University of Illinois at Chicago, Chicago, IL.,Department of General Surgery, Gastroenterological Oncology and Endocrine Surgery, Poznan University of Medical Sciences, Poznan, Poland
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23
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Zhu S, Liu J, Zheng C, Gu L, Zhu Q, Xiang J, He B, Zhou X, Liu X. Analysis of human acellular nerve allograft reconstruction of 64 injured nerves in the hand and upper extremity: a 3 year follow-up study. J Tissue Eng Regen Med 2016; 11:2314-2322. [PMID: 27098545 DOI: 10.1002/term.2130] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Revised: 11/15/2015] [Accepted: 12/10/2015] [Indexed: 11/09/2022]
Affiliation(s)
- Shuang Zhu
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
| | - Jianghui Liu
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
| | - Canbin Zheng
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
| | - Liqiang Gu
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
| | - Qingtang Zhu
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
| | - Jianping Xiang
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
| | - Bo He
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
| | - Xiang Zhou
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
| | - Xiaolin Liu
- Department of Microsurgery, Orthopedic Trauma and Hand Surgery; the First Affiliated Hospital of Sun Yat-sen University; Guangzhou People's Republic of China
- Center for Peripheral Nerve Tissue-engineering and Technology Research Guangdong; Guangzhou People's Republic of China
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24
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Fairbairn NG, Meppelink AM, Ng-Glazier J, Randolph MA, Winograd JM. Augmenting peripheral nerve regeneration using stem cells: A review of current opinion. World J Stem Cells 2015; 7:11-26. [PMID: 25621102 PMCID: PMC4300921 DOI: 10.4252/wjsc.v7.i1.11] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Revised: 09/18/2014] [Accepted: 10/27/2014] [Indexed: 02/06/2023] Open
Abstract
Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell (SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration.
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25
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Geuna S. The sciatic nerve injury model in pre-clinical research. J Neurosci Methods 2015; 243:39-46. [PMID: 25629799 DOI: 10.1016/j.jneumeth.2015.01.021] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 01/15/2015] [Accepted: 01/16/2015] [Indexed: 12/15/2022]
Abstract
In the pre-clinical view, the study of peripheral nerve repair and regeneration still needs to be carried out in animal models due to the structural complexity of this organ which can be only partly simulated in vitro. The far most used experimental model is based on the injury of the sciatic nerve, the largest nerve trunk in mammals. In this paper, the potential application of the sciatic nerve injury model in pre-clinical research is critically reviewed. This paper is aimed at helping researchers in properly employing this in vivo model for the study of nerve repair and regeneration as well as interpreting the results in a clinical translation perspective.
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Affiliation(s)
- Stefano Geuna
- Neuroscience Institute of the Cavalieri Ottolenghi Foundation & Department of Clinical and Biological Sciences, University of Turin, Italy.
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26
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Nijhuis THJ. Venous Conduit as a Model for Nerve Regeneration. Plast Reconstr Surg 2015. [DOI: 10.1007/978-1-4471-6335-0_59] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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27
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Cwykiel J, Tfaily EB, Siemionow MZ. Cellular Therapies in Nerve Regeneration. Plast Reconstr Surg 2015. [DOI: 10.1007/978-1-4471-6335-0_76] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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28
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A Contemporary Overview of Peripheral Nerve Research from Cleveland Clinic Microsurgery Laboratory. Plast Reconstr Surg 2015. [DOI: 10.1007/978-1-4471-6335-0_50] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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29
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Gattazzo F, De Maria C, Whulanza Y, Taverni G, Ahluwalia A, Vozzi G. Realisation and characterization of conductive hollow fibers for neuronal tissue engineering. J Biomed Mater Res B Appl Biomater 2014; 103:1107-19. [DOI: 10.1002/jbm.b.33297] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 08/16/2014] [Accepted: 09/12/2014] [Indexed: 12/13/2022]
Affiliation(s)
- Francesca Gattazzo
- Research Center “E. Piaggio,” University of Pisa; Largo Lucio Lazzarino 1 Pisa 56122 Italy
- Department of Molecular Medicine; University of Padova; Padova 35131 Italy
| | - Carmelo De Maria
- Research Center “E. Piaggio,” University of Pisa; Largo Lucio Lazzarino 1 Pisa 56122 Italy
- Department of Ingegneria dell'Informazione; University of Pisa; Via G. Caruso 16 Pisa 56122 Italy
| | - Yudan Whulanza
- Research Center “E. Piaggio,” University of Pisa; Largo Lucio Lazzarino 1 Pisa 56122 Italy
| | - Gemma Taverni
- Research Center “E. Piaggio,” University of Pisa; Largo Lucio Lazzarino 1 Pisa 56122 Italy
| | - Arti Ahluwalia
- Research Center “E. Piaggio,” University of Pisa; Largo Lucio Lazzarino 1 Pisa 56122 Italy
- Department of Ingegneria dell'Informazione; University of Pisa; Via G. Caruso 16 Pisa 56122 Italy
| | - Giovanni Vozzi
- Research Center “E. Piaggio,” University of Pisa; Largo Lucio Lazzarino 1 Pisa 56122 Italy
- Department of Ingegneria dell'Informazione; University of Pisa; Via G. Caruso 16 Pisa 56122 Italy
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30
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Martinez AMB, Goulart CDO, Ramalho BDS, Oliveira JT, Almeida FM. Neurotrauma and mesenchymal stem cells treatment: From experimental studies to clinical trials. World J Stem Cells 2014; 6:179-94. [PMID: 24772245 PMCID: PMC3999776 DOI: 10.4252/wjsc.v6.i2.179] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 02/26/2014] [Accepted: 03/11/2014] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cell (MSC) therapy has attracted the attention of scientists and clinicians around the world. Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve injury. These effects are believed to be due to their ability to differentiate into other cell lineages, modulate inflammatory and immunomodulatory responses, reduce cell apoptosis, secrete several neurotrophic factors and respond to tissue injury, among others. There are many pre-clinical studies on MSC treatment for spinal cord injury (SCI) and peripheral nerve injuries. However, the same is not true for clinical trials, particularly those concerned with nerve trauma, indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve lesions. As for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental studies. For these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive outcomes. This review is based on pre-clinical studies and clinical trials available in the literature from 2010 until now. At the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves, respectively.
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Affiliation(s)
- Ana Maria Blanco Martinez
- Ana Maria Blanco Martinez, Camila de Oliveira Goulart, Bruna dos Santos Ramalho, Júlia Teixeira Oliveira, Fernanda Martins Almeida, Laboratory of Neurodegeneration and Repair, Institute of Biomedical Sciences, Health Science Center, 21941-902, Rio de Janeiro, Brazil
| | - Camila de Oliveira Goulart
- Ana Maria Blanco Martinez, Camila de Oliveira Goulart, Bruna dos Santos Ramalho, Júlia Teixeira Oliveira, Fernanda Martins Almeida, Laboratory of Neurodegeneration and Repair, Institute of Biomedical Sciences, Health Science Center, 21941-902, Rio de Janeiro, Brazil
| | - Bruna Dos Santos Ramalho
- Ana Maria Blanco Martinez, Camila de Oliveira Goulart, Bruna dos Santos Ramalho, Júlia Teixeira Oliveira, Fernanda Martins Almeida, Laboratory of Neurodegeneration and Repair, Institute of Biomedical Sciences, Health Science Center, 21941-902, Rio de Janeiro, Brazil
| | - Júlia Teixeira Oliveira
- Ana Maria Blanco Martinez, Camila de Oliveira Goulart, Bruna dos Santos Ramalho, Júlia Teixeira Oliveira, Fernanda Martins Almeida, Laboratory of Neurodegeneration and Repair, Institute of Biomedical Sciences, Health Science Center, 21941-902, Rio de Janeiro, Brazil
| | - Fernanda Martins Almeida
- Ana Maria Blanco Martinez, Camila de Oliveira Goulart, Bruna dos Santos Ramalho, Júlia Teixeira Oliveira, Fernanda Martins Almeida, Laboratory of Neurodegeneration and Repair, Institute of Biomedical Sciences, Health Science Center, 21941-902, Rio de Janeiro, Brazil
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31
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Geuna S, Tos P, Titolo P, Ciclamini D, Beningo T, Battiston B. Update on nerve repair by biological tubulization. J Brachial Plex Peripher Nerve Inj 2014; 9:3. [PMID: 24606921 PMCID: PMC3953745 DOI: 10.1186/1749-7221-9-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Accepted: 03/02/2014] [Indexed: 12/18/2022] Open
Abstract
Many surgical techniques are available for bridging peripheral nerve defects. Autologous nerve grafts are the current gold standard for most clinical conditions. In selected cases, alternative types of conduits can be used. Although most efforts are today directed towards the development of artificial synthetic nerve guides, the use of non-nervous autologous tissue-based conduits (biological tubulization) can still be considered a valuable alternative to nerve autografts. In this paper we will overview the advancements in biological tubulization of nerve defects, with either mono-component or multiple-component autotransplants, with a special focus on the use of a vein segment filled with skeletal muscle fibers, a technique that has been widely investigated in our laboratory and that has already been successfully introduced in the clinical practice.
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Affiliation(s)
- Stefano Geuna
- Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), University of Turin, Turin 10043, Italy
- Department of Clinical and Biological Sciences, University of Turin, Turin 10043, Italy
| | - Pierluigi Tos
- Department of Traumatology, Microsurgery Unit, CTO Hospital, Turin, Italy
| | - Paolo Titolo
- UOC Traumatology–Reconstructive Microsurgery, Department of Orthopaedics and Traumatology, CTO Hospital, Torino, Italy
| | - Davide Ciclamini
- Department of Traumatology, Microsurgery Unit, CTO Hospital, Turin, Italy
| | - Teresa Beningo
- Department of Traumatology, Microsurgery Unit, CTO Hospital, Turin, Italy
| | - Bruno Battiston
- Department of Traumatology, Microsurgery Unit, CTO Hospital, Turin, Italy
- UOC Traumatology–Reconstructive Microsurgery, Department of Orthopaedics and Traumatology, CTO Hospital, Torino, Italy
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