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Ferreira LVDO, Roballo KCS, Amorim RM. Mesenchymal stem cell-based therapy for peripheral nerve injuries: A promise or reality? World J Stem Cells 2025; 17:107833. [DOI: 10.4252/wjsc.v17.i6.107833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2025] [Revised: 04/23/2025] [Accepted: 06/09/2025] [Indexed: 06/25/2025] Open
Abstract
Peripheral nerve injuries (PNI) that result in nerve gaps represent a major clinical challenge, frequently leading to long-term disability and a diminished quality of life for affected individuals. Despite advances in surgical techniques, functional recovery remains limited, highlighting the need for innovative therapeutic strategies. Mesenchymal stem cells (MSCs) have emerged as a promising avenue for nerve repair due to their regenerative, immunomodulatory, and neuroprotective properties. Thus, this review explored current approaches utilizing MSCs in the treatment of PNI, emphasizing their potential to enhance nerve regeneration and functional recovery. Furthermore, tissue engineering and transdifferentiation of MSCs into Schwann-like cells offer a versatile strategy to optimize therapeutic effects, paving the way for personalized medicine. Nevertheless, challenges persist regarding the clinical application of MSCs in PNI, including transplant safety, delivery methods, optimal dosing, and ethical considerations. A deeper understanding of the mechanisms underlying MSC action in PNI may contribute to more effective treatment protocols in the management of peripheral nerve defects.
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Affiliation(s)
- Lucas Vinícius de Oliveira Ferreira
- Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University, Botucatu 18618-681, São Paulo, Brazil
- Center for Translational Research in Regenerative Medicine, Institute of Biotechnology, São Paulo State University, Botucatu 18607-440, São Paulo, Brazil
| | - Kelly Cristine Santos Roballo
- Department of Biomedical Sciences and Pathobiology, Virginia Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, United States
- Biomedical Affairs and Research, Edward Via College of Osteopathic Medicine, Blacksburg, VA 24060, United States
| | - Rogério Martins Amorim
- Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University, Botucatu 18618-681, São Paulo, Brazil
- Center for Translational Research in Regenerative Medicine, Institute of Biotechnology, São Paulo State University, Botucatu 18607-440, São Paulo, Brazil
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Ferreira LVDO, Amorim RM. Perspectives on Schwann-like cells derived from bone marrow-mesenchymal stem cells: Advancing peripheral nerve injury therapies. World J Stem Cells 2025; 17:102702. [PMID: 40061268 PMCID: PMC11885942 DOI: 10.4252/wjsc.v17.i2.102702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/18/2024] [Accepted: 01/18/2025] [Indexed: 02/24/2025] Open
Abstract
Peripheral nerve injuries are clinical conditions that often result in functional deficits, compromising patient quality of life. Given the relevance of these injuries, new treatment strategies are constantly being investigated. Although mesenchymal stem cells already demonstrate therapeutic potential due to their paracrine action, the transdifferentiation of these cells into Schwann-like cells (SLCs) represents a significant advancement in nerve injury therapy. Recent studies indicate that SLCs can mimic the functions of Schwann cells, with promising results in animal models. However, challenges remain, such as the diversity of transdifferentiation protocols and the scalability of these therapies for clinical applications. A recent study by Zou et al provided a comprehensive overview of the role of bone marrow-derived mesenchymal stem cells in the treatment of peripheral nerve injuries. Therefore, we would like to discuss and explore the use of SLCs derived from bone marrow-derived mesenchymal stem cells in more detail as a promising alternative in the field of nerve regeneration.
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Affiliation(s)
- Lucas Vinícius de Oliveira Ferreira
- Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu 18618-681, São Paulo, Brazil.
| | - Rogério Martins Amorim
- Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu 18618-681, São Paulo, Brazil
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Tai Y, Tonmoy TI, Win S, Brinkley NT, Park BH, Nam J. Enhanced peripheral nerve regeneration by mechano-electrical stimulation. NPJ Regen Med 2023; 8:57. [PMID: 37848428 PMCID: PMC10582163 DOI: 10.1038/s41536-023-00334-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 09/29/2023] [Indexed: 10/19/2023] Open
Abstract
To address limitations in current approaches for treating large peripheral nerve defects, the presented study evaluated the feasibility of functional material-mediated physical stimuli on peripheral nerve regeneration. Electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) nanofibers were utilized to deliver mechanical actuation-activated electrical stimulation to nerve cells/tissues in a non-invasive manner. Using morphologically and piezoelectrically optimized nanofibers for neurite extension and Schwann cell maturation based on in vitro experiments, piezoelectric nerve conduits were synthesized and implanted in a rat sciatic nerve transection model to bridge a critical-sized sciatic nerve defect (15 mm). A therapeutic shockwave system was utilized to periodically activate the piezoelectric effect of the implanted nerve conduit on demand. The piezoelectric nerve conduit-mediated mechano-electrical stimulation (MES) induced enhanced peripheral nerve regeneration, resulting in full axon reconnection with myelin regeneration from the proximal to the distal ends over the critical-sized nerve gap. In comparison, a control group, in which the implanted piezoelectric conduits were not activated in vivo, failed to exhibit such nerve regeneration. In addition, at both proximal and distal ends of the implanted conduits, a decreased number of damaged myelination (ovoids), an increased number of myelinated nerves, and a larger axonal diameter were observed under the MES condition as compared to the control condition. Furthermore, unlike the control group, the MES condition exhibited a superior functional nerve recovery, assessed by walking track analysis and polarization-sensitive optical coherence tomography, demonstrating the significant potential of the piezoelectric conduit-based physical stimulation approach for the treatment of peripheral nerve injury.
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Affiliation(s)
- Youyi Tai
- Department of Bioengineering, University of California, Riverside, CA, 92521, USA
| | | | - Shwe Win
- Department of Bioengineering, University of California, Riverside, CA, 92521, USA
| | - Natasha T Brinkley
- Department of Bioengineering, University of California, Riverside, CA, 92521, USA
| | - B Hyle Park
- Department of Bioengineering, University of California, Riverside, CA, 92521, USA
| | - Jin Nam
- Department of Bioengineering, University of California, Riverside, CA, 92521, USA.
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Takeya H, Itai S, Kimura H, Kurashina Y, Amemiya T, Nagoshi N, Iwamoto T, Sato K, Shibata S, Matsumoto M, Onoe H, Nakamura M. Schwann cell-encapsulated chitosan-collagen hydrogel nerve conduit promotes peripheral nerve regeneration in rodent sciatic nerve defect models. Sci Rep 2023; 13:11932. [PMID: 37488180 PMCID: PMC10366170 DOI: 10.1038/s41598-023-39141-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 07/20/2023] [Indexed: 07/26/2023] Open
Abstract
Chitosan has various tissue regeneration effects. This study was designed to investigate the nerve regeneration effect of Schwann cell (SC)-encapsulated chitosan-collagen hydrogel nerve conduit (CCN) transplanted into a rat model of sciatic nerve defect. We prepared a CCN consisting of an outer layer of chitosan hydrogel and an inner layer of collagen hydrogel to encapsulate the intended cells. Rats with a 10-mm sciatic nerve defect were treated with SCs encapsulated in CCN (CCN+), CCN without SCs (CCN-), SC-encapsulated silicone tube (silicone+), and autologous nerve transplanting (auto). Behavioral and histological analyses indicated that motor functional recovery, axonal regrowth, and myelination of the CCN+ group were superior to those of the CCN- and silicone+ groups. Meanwhile, the CCN- and silicone+ groups showed no significant differences in the recovery of motor function and nerve histological restoration. In conclusion, SC-encapsulated CCN has a synergistic effect on peripheral nerve regeneration, especially axonal regrowth and remyelination of host SCs. In the early phase after transplantation, SC-encapsulated CCNs have a positive effect on recovery. Therefore, using SC-encapsulated CCNs may be a promising approach for massive peripheral nerve defects.
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Affiliation(s)
- Hiroaki Takeya
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Shun Itai
- Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-Ku, Yokohama-Shi, Kanagawa, 223-8522, Japan
- Division of Medical Science, Graduate School of Biomedical Engineering, Tohoku University, 1-1 Seiryomachi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Hiroo Kimura
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-Ku, Tokyo, 160-8582, Japan.
| | - Yuta Kurashina
- Division of Advanced Mechanical Systems Engineering, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei-Shi, Tokyo, 184-8588, Japan
| | - Tsuyoshi Amemiya
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Narihito Nagoshi
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Takuji Iwamoto
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Kazuki Sato
- Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinanomachi Shinjuku-Ku, Tokyo, Japan
| | - Shinsuke Shibata
- Division of Microscopic Anatomy, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-Ku, Niigata, 951-8510, Japan
| | - Morio Matsumoto
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Hiroaki Onoe
- Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-Ku, Yokohama-Shi, Kanagawa, 223-8522, Japan
| | - Masaya Nakamura
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi Shinjuku-Ku, Tokyo, 160-8582, Japan
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Tam KW, Wong CY, Wu KLK, Lam G, Liang X, Wong WT, Li MTS, Liu WY, Cai S, Shea GKH, Shum DKY, Chan YS. IPSC-Derived Sensory Neurons Directing Fate Commitment of Human BMSC-Derived Schwann Cells: Applications in Traumatic Neural Injuries. Cells 2023; 12:1479. [PMID: 37296600 PMCID: PMC10253081 DOI: 10.3390/cells12111479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/16/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
The in vitro derivation of Schwann cells from human bone marrow stromal cells (hBMSCs) opens avenues for autologous transplantation to achieve remyelination therapy for post-traumatic neural regeneration. Towards this end, we exploited human induced pluripotent stem-cell-derived sensory neurons to direct Schwann-cell-like cells derived from among the hBMSC-neurosphere cells into lineage-committed Schwann cells (hBMSC-dSCs). These cells were seeded into synthetic conduits for bridging critical gaps in a rat model of sciatic nerve injury. With improvement in gait by 12-week post-bridging, evoked signals were also detectable across the bridged nerve. Confocal microscopy revealed axially aligned axons in association with MBP-positive myelin layers across the bridge in contrast to null in non-seeded controls. Myelinating hBMSC-dSCs within the conduit were positive for both MBP and human nucleus marker HuN. We then implanted hBMSC-dSCs into the contused thoracic cord of rats. By 12-week post-implantation, significant improvement in hindlimb motor function was detectable if chondroitinase ABC was co-delivered to the injured site; such cord segments showed axons myelinated by hBMSC-dSCs. Results support translation into a protocol by which lineage-committed hBMSC-dSCs become available for motor function recovery after traumatic injury to both peripheral and central nervous systems.
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Affiliation(s)
- Kin-Wai Tam
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Cheuk-Yin Wong
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Kenneth Lap-Kei Wu
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Guy Lam
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Xiaotong Liang
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Wai-Ting Wong
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Maximilian Tak-Sui Li
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Wing-Yui Liu
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Sa Cai
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
| | - Graham Ka-Hon Shea
- Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;
| | - Daisy Kwok-Yan Shum
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China
| | - Ying-Shing Chan
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; (K.-W.T.); (C.-Y.W.); (K.L.-K.W.); (G.L.); (X.L.); (W.-T.W.); (M.T.-S.L.); (W.-Y.L.); (S.C.)
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China
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6
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Cho YH, Seo TB. Effect of concurrent aerobic exercise and bone marrow stromal cell transplantation on time-dependent changes of myogenic differentiation-related cascades in soleus muscle after sciatic nerve injury. J Exerc Rehabil 2023; 19:11-18. [PMID: 36910676 PMCID: PMC9993002 DOI: 10.12965/jer.2346004.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 01/09/2023] [Indexed: 02/25/2023] Open
Abstract
The purpose of this study was to investigate the time-dependent alteration in whether concurrent aerobic exercise and bone marrow stromal cell (BMSC) engraftment could regulate myogenic differentiation-related signaling pathway in the soleus up to 35 days after sciatic nerve injury (SNI). The rats were divided as follows: the normal control (CON, n=5), sedentary group (SED, n=20), treadmill exercise group (TEX, n=20), BMSC transplantation group (BMSC, n=20), TEX+BMSC transplantation group (TEX+BMSC, n=20) 7, 14, 21, and 35 days after SNI. SNI was applied into the thigh and treadmill exercise was comprised of walking at a speed of 4 to 8 m/min for 30 min once a day. Harvested BMSC at a density of 5×106 in 50-μL phosphate-buff-ered saline was injected into the injury site. Phosphorylated (p) extracellular signal-regulated kinase 1/2 expression was dramatically upregulated in BMSC and BMSC+EX groups from 21 days after SNI compared to those in the SED group. P-ribosomal s6 kinase (RSK) was sharply increased 14 days later, and then rapidly downregulated from day 21, whereas TEX, BMSC and TEX+ BMSC groups significantly kept up expression levels of p-RSK until 35 days post injury than SED group. TEX+BMSC group significantly increased activation of protein kinase B-mammalian target of rapamycin in the soleus from day 14 and myoblast determination protein 1-myogen-in pathways was activated in TEX+BMSC group from day 21. Present findings provide information that combined intervention of aerobic exercise and BMSC transplantation might be a reliable therapeutic strategy for overcoming the morphological and functional problems in denervated soleus muscle.
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Affiliation(s)
- Yeong-Hyun Cho
- Department of Kinesiology, College of Natural Science, Jeju National University, Jeju, Korea
| | - Tae-Beom Seo
- Department of Kinesiology, College of Natural Science, Jeju National University, Jeju, Korea
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7
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Reshamwala R, Shah M. Regenerative Approaches in the Nervous System. Regen Med 2023. [DOI: 10.1007/978-981-19-6008-6_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
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8
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Li X, Zhang X, Hao M, Wang D, Jiang Z, Sun L, Gao Y, Jin Y, Lei P, Zhuo Y. The application of collagen in the repair of peripheral nerve defect. Front Bioeng Biotechnol 2022; 10:973301. [PMID: 36213073 PMCID: PMC9542778 DOI: 10.3389/fbioe.2022.973301] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/19/2022] [Indexed: 11/13/2022] Open
Abstract
Collagen is a natural polymer expressed in the extracellular matrix of the peripheral nervous system. It has become increasingly crucial in peripheral nerve reconstruction as it was involved in regulating Schwann cell behaviors, maintaining peripheral nerve functions during peripheral nerve development, and being strongly upregulated after nerve injury to promote peripheral nerve regeneration. Moreover, its biological properties, such as low immunogenicity, excellent biocompatibility, and biodegradability make it a suitable biomaterial for peripheral nerve repair. Collagen provides a suitable microenvironment to support Schwann cells’ growth, proliferation, and migration, thereby improving the regeneration and functional recovery of peripheral nerves. This review aims to summarize the characteristics of collagen as a biomaterial, analyze its role in peripheral nerve regeneration, and provide a detailed overview of the recent advances concerning the optimization of collagen nerve conduits in terms of physical properties and structure, as well as the application of the combination with the bioactive component in peripheral nerve regeneration.
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Affiliation(s)
- Xiaolan Li
- Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Xiang Zhang
- Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Ming Hao
- School of Acupuncture-Moxi Bustion and Tuina, Changchun University of Chinese Medicine, Changchun, China
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Dongxu Wang
- Laboratory Animal Center, College of Animal Science, Jilin University, Changchun, China
| | - Ziping Jiang
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Liqun Sun
- Department of Pediatrics, First Hospital of Jilin University, Changchun, China
| | - Yongjian Gao
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Ye Jin
- Department of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
| | - Peng Lei
- Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Peng Lei, ; Yue Zhuo,
| | - Yue Zhuo
- School of Acupuncture-Moxi Bustion and Tuina, Changchun University of Chinese Medicine, Changchun, China
- *Correspondence: Peng Lei, ; Yue Zhuo,
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9
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Su Q, Nasser MI, He J, Deng G, Ouyang Q, Zhuang D, Deng Y, Hu H, Liu N, Li Z, Zhu P, Li G. Engineered Schwann Cell-Based Therapies for Injury Peripheral Nerve Reconstruction. Front Cell Neurosci 2022; 16:865266. [PMID: 35602558 PMCID: PMC9120533 DOI: 10.3389/fncel.2022.865266] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 04/04/2022] [Indexed: 12/12/2022] Open
Abstract
Compared with the central nervous system, the adult peripheral nervous system possesses a remarkable regenerative capacity, which is due to the strong plasticity of Schwann cells (SCs) in peripheral nerves. After peripheral nervous injury, SCs de-differentiate and transform into repair phenotypes, and play a critical role in axonal regeneration, myelin formation, and clearance of axonal and myelin debris. In view of the limited self-repair capability of SCs for long segment defects of peripheral nerve defects, it is of great clinical value to supplement SCs in necrotic areas through gene modification or stem cell transplantation or to construct tissue-engineered nerve combined with bioactive scaffolds to repair such tissue defects. Based on the developmental lineage of SCs and the gene regulation network after peripheral nerve injury (PNI), this review summarizes the possibility of using SCs constructed by the latest gene modification technology to repair PNI. The therapeutic effects of tissue-engineered nerve constructed by materials combined with Schwann cells resembles autologous transplantation, which is the gold standard for PNI repair. Therefore, this review generalizes the research progress of biomaterials combined with Schwann cells for PNI repair. Based on the difficulty of donor sources, this review also discusses the potential of “unlimited” provision of pluripotent stem cells capable of directing differentiation or transforming existing somatic cells into induced SCs. The summary of these concepts and therapeutic strategies makes it possible for SCs to be used more effectively in the repair of PNI.
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Affiliation(s)
- Qisong Su
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Moussa Ide Nasser
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangzhou, China
| | - Jiaming He
- School of Basic Medical Science, Shandong University, Jinan, China
| | - Gang Deng
- Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Qing Ouyang
- Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Donglin Zhuang
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuzhi Deng
- Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangzhou, China
- The First Clinical College, Guangdong Medical University, Zhanjiang, China
| | - Haoyun Hu
- Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangzhou, China
- The First Clinical College, Guangdong Medical University, Zhanjiang, China
| | - Nanbo Liu
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
| | - Zhetao Li
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Ping Zhu
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
- The First Clinical College, Guangdong Medical University, Zhanjiang, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Structural Heart Disease, Guangzhou, China
- *Correspondence: Ping Zhu,
| | - Ge Li
- Medical Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangzhou, China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
- Guangdong Provincial Key Laboratory of Structural Heart Disease, Guangzhou, China
- Ge Li,
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10
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Wang Q, Chen FY, Ling ZM, Su WF, Zhao YY, Chen G, Wei ZY. The Effect of Schwann Cells/Schwann Cell-Like Cells on Cell Therapy for Peripheral Neuropathy. Front Cell Neurosci 2022; 16:836931. [PMID: 35350167 PMCID: PMC8957843 DOI: 10.3389/fncel.2022.836931] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 02/02/2022] [Indexed: 12/11/2022] Open
Abstract
Peripheral neuropathy is a common neurological issue that leads to sensory and motor disorders. Over time, the treatment for peripheral neuropathy has primarily focused on medications for specific symptoms and surgical techniques. Despite the different advantages of these treatments, functional recovery remains less than ideal. Schwann cells, as the primary glial cells in the peripheral nervous system, play crucial roles in physiological and pathological conditions by maintaining nerve structure and functions and secreting various signaling molecules and neurotrophic factors to support both axonal growth and myelination. In addition, stem cells, including mesenchymal stromal cells, skin precursor cells and neural stem cells, have the potential to differentiate into Schwann-like cells to perform similar functions as Schwann cells. Therefore, accumulating evidence indicates that Schwann cell transplantation plays a crucial role in the resolution of peripheral neuropathy. In this review, we summarize the literature regarding the use of Schwann cell/Schwann cell-like cell transplantation for different peripheral neuropathies and the potential role of promoting nerve repair and functional recovery. Finally, we discuss the limitations and challenges of Schwann cell/Schwann cell-like cell transplantation in future clinical applications. Together, these studies provide insights into the effect of Schwann cells/Schwann cell-like cells on cell therapy and uncover prospective therapeutic strategies for peripheral neuropathy.
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Affiliation(s)
- Qian Wang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Fang-Yu Chen
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Zhuo-Min Ling
- Medical School of Nantong University, Nantong, China
| | - Wen-Feng Su
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Ya-Yu Zhao
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Gang Chen
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
- Medical School of Nantong University, Nantong, China
- Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China
- *Correspondence: Gang Chen,
| | - Zhong-Ya Wei
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China
- Zhong-Ya Wei,
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11
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Wu SH, Liao YT, Huang CH, Chen YC, Chiang ER, Wang JP. Comparison of the Confluence-Initiated Neurogenic Differentiation Tendency of Adipose-Derived and Bone Marrow-Derived Mesenchymal Stem Cells. Biomedicines 2021; 9:biomedicines9111503. [PMID: 34829732 PMCID: PMC8615071 DOI: 10.3390/biomedicines9111503] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 10/18/2021] [Accepted: 10/18/2021] [Indexed: 12/27/2022] Open
Abstract
Adipose-derived mesenchymal stem cells (ADSCs), which tended to neurogenically differentiate spontaneously after achieving high confluence, were observed. Human ADSCs reaching 80% confluence were cultured in DMEM without an inducing factor for 24 h and then maintained in DMEM plus 1% FBS medium for 7 days. The neurogenic, adipogenic, and osteogenic genes of the factor-induced and confluence-initiated differentiation of the ADSCs and bone marrow-derived mesenchymal stem cells (BMSCs) at passages 3 to 5 were determined and compared using RT-qPCR, and the neurogenic differentiation was confirmed using immunofluorescent staining. In vitro tests revealed that the RNA and protein expression of neuronal markers, including class III β-tubulin (TUBB3), microtubule-associated protein 2 (MAP2), neurofilament medium polypeptide (NEFM), neurofilament heavy polypeptide (NEFH), and neurofilament light polypeptide (NEFL), had been enhanced in the confluence-initiated differentiation of the ADSCs. In addition, the expressions of neurotrophins, such as the nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), were also elevated in the confluence-initiated differentiation of the ADSCs. However, the confluent ADSCs did not show a tendency toward spontaneous adipogenic and osteogenic differentiation. Moreover, compared with the confluent ADSCs, the tendency of spontaneous neurogenic, adipogenic, and osteogenic differentiation of the confluent human bone marrow mesenchymal stem cells (BMSCs) was not observed. The results indicated that ADSCs had the potential to spontaneously differentiate into neuron-like cells during the confluent culture period; however, this tendency was not observed in BMSCs.
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Affiliation(s)
- Szu-Hsien Wu
- Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan; (S.-H.W.); (C.-H.H.)
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
- Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, National Defense Medical Center, Taipei 112, Taiwan
| | - Yu-Ting Liao
- Department of Orthopaedics & Traumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan;
| | - Chi-Han Huang
- Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan; (S.-H.W.); (C.-H.H.)
| | - Yi-Chou Chen
- Department of Orthopedics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 330, Taiwan;
| | - En-Rung Chiang
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
- Department of Orthopaedics & Traumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan;
| | - Jung-Pan Wang
- Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
- Department of Orthopaedics & Traumatology, Taipei Veterans General Hospital, Taipei 112, Taiwan;
- Correspondence: ; Tel.: +886-2-2875-7557; Fax: +886-2-2875-7657
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12
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Ucar B. Natural biomaterials in brain repair: A focus on collagen. Neurochem Int 2021; 146:105033. [PMID: 33785419 DOI: 10.1016/j.neuint.2021.105033] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 03/07/2021] [Accepted: 03/22/2021] [Indexed: 12/16/2022]
Abstract
Biomaterials derived from natural resources have increasingly been used for versatile applications in the central nervous system (CNS). Thanks to their biocompatibility and biodegradability, natural biomaterials offer vast possibilities for future clinical repair strategies for the CNS. These materials can be used for diverse applications such as hydrogels to fill the tissue cavities, microparticles to deliver drugs across the blood-brain barrier, and scaffolds to transplant stem cells. In this review, various uses of prominent protein and polysaccharide biomaterials, with a special focus on collagen, in repair and regenerative applications for the brain are summarized together with their individual advantages and disadvantages.
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Affiliation(s)
- Buket Ucar
- Laboratory of Psychiatry and Experimental Alzheimer's Research, Medical University of Innsbruck, Austria.
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13
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Wang JP, Liao YT, Wu SH, Chiang ER, Hsu SH, Tseng TC, Hung SC. Mesenchymal stem cells from a hypoxic culture improve nerve regeneration. J Tissue Eng Regen Med 2020; 14:1804-1814. [PMID: 32976700 DOI: 10.1002/term.3136] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 08/27/2020] [Accepted: 09/10/2020] [Indexed: 12/31/2022]
Abstract
Repairing the peripheral nerves following a segmental defect injury remains surgically challenging. Because of some disadvantages of nerve grafts, nerve regeneration, such as conduits combined with bone marrow-derived mesenchymal stem cells (BMSCs), may serve as an alternative. BMSCs expand under hypoxic conditions, decrease in senescence, and increase in proliferation and differentiation potential into the bone, fat, and cartilage. The purpose of this study was to investigate whether BMSCs increased the neuronal differentiation potential following expansion under hypoxic conditions. Isolated human BMSCs (hBMSCs) expand under hypoxia or normoxia, and neuronal differentiation proceeds under normoxia. in vitro tests revealed hypoxia culture enhanced the RNA and protein expression of neuronal markers. The electrophysiology of hBMSC-differentiated neuron-like cells was also enhanced by the hypoxia culturing. Our animal model indicated that the potential treatment of hypoxic rat BMSCs (rBMSCs) was better than that of normoxic rBMSCs because the conduit with the hypoxic rBMSCs injection demonstrated the highest recovery rate of gastrocnemius muscle weights. There were more toluidine blue-stained myelinated nerve fibers in the hypoxic rBMSCs group than in the normoxic group. To sum up, BMSCs cultured under hypoxia increased the potential of neuronal differentiation both in vivo and in vitro.
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Affiliation(s)
- Jung-Pan Wang
- Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Ting Liao
- Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Szu-Hsien Wu
- Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - En-Rung Chiang
- Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shan-Hui Hsu
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan
| | - Ting-Chen Tseng
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan
| | - Shih-Chieh Hung
- Graduate Institute of New Drug Development, Biomedical Sciences, China Medical University, Taichung, Taiwan
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14
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Hopf A, Schaefer DJ, Kalbermatten DF, Guzman R, Madduri S. Schwann Cell-Like Cells: Origin and Usability for Repair and Regeneration of the Peripheral and Central Nervous System. Cells 2020; 9:E1990. [PMID: 32872454 PMCID: PMC7565191 DOI: 10.3390/cells9091990] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 08/06/2020] [Accepted: 08/22/2020] [Indexed: 12/14/2022] Open
Abstract
Functional recovery after neurotmesis, a complete transection of the nerve fiber, is often poor and requires a surgical procedure. Especially for longer gaps (>3 mm), end-to-end suturing of the proximal to the distal part is not possible, thus requiring nerve graft implantation. Artificial nerve grafts, i.e., hollow fibers, hydrogels, chitosan, collagen conduits, and decellularized scaffolds hold promise provided that these structures are populated with Schwann cells (SC) that are widely accepted to promote peripheral and spinal cord regeneration. However, these cells must be collected from the healthy peripheral nerves, resulting in significant time delay for treatment and undesired morbidities for the donors. Therefore, there is a clear need to explore the viable source of cells with a regenerative potential similar to SC. For this, we analyzed the literature for the generation of Schwann cell-like cells (SCLC) from stem cells of different origins (i.e., mesenchymal stem cells, pluripotent stem cells, and genetically programmed somatic cells) and compared their biological performance to promote axonal regeneration. Thus, the present review accounts for current developments in the field of SCLC differentiation, their applications in peripheral and central nervous system injury, and provides insights for future strategies.
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Affiliation(s)
- Alois Hopf
- Department of Biomedical Engineering, University of Basel, Gewerbestrasse 14, 4123 Allschwil, Switzerland; (A.H.); (D.F.K.)
- Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland; (D.J.S.); (R.G.)
| | - Dirk J. Schaefer
- Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland; (D.J.S.); (R.G.)
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland
| | - Daniel F. Kalbermatten
- Department of Biomedical Engineering, University of Basel, Gewerbestrasse 14, 4123 Allschwil, Switzerland; (A.H.); (D.F.K.)
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland
| | - Raphael Guzman
- Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland; (D.J.S.); (R.G.)
- Department of Neurosurgery, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland
| | - Srinivas Madduri
- Department of Biomedical Engineering, University of Basel, Gewerbestrasse 14, 4123 Allschwil, Switzerland; (A.H.); (D.F.K.)
- Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland; (D.J.S.); (R.G.)
- Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland
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15
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Yang X, Ji C, Liu X, Zheng C, Zhang Y, Shen R, Zhou Z. The significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the development of terminally differentiated Schwann cells in vitro. Int J Neurosci 2020; 132:171-180. [PMID: 32757877 DOI: 10.1080/00207454.2020.1806266] [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: 10/23/2022]
Abstract
PURPOSE The purpose of this study was to explore the significance of the neuregulin-1/ErbB signaling pathway and its effect on Sox10 expression in the course of the differentiation of mouse bone marrow mesenchymal stem cells into Schwann-like cells in vitro. MATERIALS AND METHODS The experiment was conducted with three groups-control, TAK 165, and HRG-off. In the control group, we used the classical induction method of adding β-ME, RA, FSK, b-FGF, PDGF, and neuregulin (HRG); the cells were collected on the 7th day. Using the same basic protocol as the control group, the specific ErbB2 inhibitor mubritinib (TAK 165) was added to block the neuregulin-1/ErbB pathway in the TAK 165 group, while HRG was not added in the HRG-off group. We detected the degree of differentiation of stem cells into Schwann-like cells by using RT-PCR to examine the expression of Sox10, NRG-1, ErbB2, ErbB3, and ErbB4 and by using immunofluorescence staining to examine the Schwann cell marker S100B, Glial Fibrillary Acidic Protein (GFAP) and P75. RESULTS Our results showed that the proliferation of Schwann cells was reduced and apoptosis was increased in the TAK 165 group and the HRG-off group. Sox10 was stably expressed and NRG-1, ErbB2, and ErbB3 increased in the control group. However, the expression of Sox10 in the TAK 165 group was obviously decreased at the end of induced differentiation; meanwhile, the degree of stem cell differentiation also decreased. CONCLUSIONS the neuregulin-1/ErbB signaling pathway plays an important role in the differentiation of bone marrow mesenchymal stem cells into Schwann-like cells and can promote the maintenance of Sox10 。.
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Affiliation(s)
- Xizhong Yang
- Department of Human Anatomy, Medical College of Qingdao University, Qingdao, P.R China.,Department of Orthopaedics, Jimo people's Hospital, Qingdao, P.R China
| | - Cuijie Ji
- Department of Orthopaedics, Jimo people's Hospital, Qingdao, P.R China
| | - Xinyue Liu
- Department of Human Anatomy, Medical College of Qingdao University, Qingdao, P.R China
| | - Chaoqun Zheng
- Department of Human Anatomy, Medical College of Qingdao University, Qingdao, P.R China
| | - Yanxin Zhang
- Department of Human Anatomy, Medical College of Qingdao University, Qingdao, P.R China
| | - Ruowu Shen
- Department of Human Anatomy, Medical College of Qingdao University, Qingdao, P.R China
| | - Zangong Zhou
- Department of Anesthesiology, Affiliated Hospital of Qingdao University, Qingdao, P.R China
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16
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Zhou G, Chang W, Zhou X, Chen Y, Dai F, Anwar A, Yu X. Nanofibrous Nerve Conduits with Nerve Growth Factors and Bone Marrow Stromal Cells Pre-Cultured in Bioreactors for Peripheral Nerve Regeneration. ACS APPLIED MATERIALS & INTERFACES 2020; 12:16168-16177. [PMID: 32182427 DOI: 10.1021/acsami.0c04191] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Peripheral nerve injury (PNI) was the leading cause of permanent dysfunction in movement and sensation. Synthesized nerve guide conduits (NGCs) with Schwann Cells (SCs) can help peripheral nerve regeneration. However, poor accessibility of SCs and lack of full coverage of seeded cells on NGCs can lead to failure of nerve regeneration across long gaps and full functional recovery. To overcome these limitations, bone marrow stromal cells (BMSCs) and a novel culture method were proposed in the current study. BMSCs were harvested and seeded on a never growth factor (NGF)-loaded PCL nanofibrous NGCs and cultured with a rotary cell culture system (RCCS) before implantation. The NGCs were tested in vitro with PC-12 cells to validate the bioactivity of released NGF and to access its ability to promote neurite extension. Also, the NGCs were tested in vivo with rat sciatic nerve model to exam its potential in bridging the long gap (15 mm segmental defect). The efficacy of the NGCs was investigated based on the results of the functional test, electrophysiology test, muscle atrophy, and histological analysis. The results of in vitro PC-12 cell study confirmed the bioactivity of released NGF and showed a significant increase in the neurite extension with the help of PEG-diamine and BSA. These results showed that the novel loading method could preserve the bioactivity of growth factors and achieve a sustained release in vitro. Besides, the results of the in vivo study exhibited a significant increase with the combination of all additives. These results showed that with the help of NGF and RCCS, the NGCs with the seeded BMSCs could enhance peripheral nerve regeneration across long nerve injury gaps.
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Affiliation(s)
- Gan Zhou
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States
| | - Wei Chang
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States
| | - Xiaqing Zhou
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States
| | - Yifan Chen
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States
| | - Futao Dai
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States
| | - Aneela Anwar
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States
| | - Xiaojun Yu
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States
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17
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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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18
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Carvalho CR, Oliveira JM, Reis RL. Modern Trends for Peripheral Nerve Repair and Regeneration: Beyond the Hollow Nerve Guidance Conduit. Front Bioeng Biotechnol 2019; 7:337. [PMID: 31824934 PMCID: PMC6882937 DOI: 10.3389/fbioe.2019.00337] [Citation(s) in RCA: 182] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 10/30/2019] [Indexed: 12/13/2022] Open
Abstract
Peripheral nerve repair and regeneration remains among the greatest challenges in tissue engineering and regenerative medicine. Even though peripheral nerve injuries (PNIs) are capable of some degree of regeneration, frail recovery is seen even when the best microsurgical technique is applied. PNIs are known to be very incapacitating for the patient, due to the deprivation of motor and sensory abilities. Since there is no optimal solution for tackling this problem up to this day, the evolution in the field is constant, with innovative designs of advanced nerve guidance conduits (NGCs) being reported every day. As a basic concept, a NGC should act as a physical barrier from the external environment, concomitantly acting as physical guidance for the regenerative axons across the gap lesion. NGCs should also be able to retain the naturally released nerve growth factors secreted by the damaged nerve stumps, as well as reducing the invasion of scar tissue-forming fibroblasts to the injury site. Based on the neurobiological knowledge related to the events that succeed after a nerve injury, neuronal subsistence is subjected to the existence of an ideal environment of growth factors, hormones, cytokines, and extracellular matrix (ECM) factors. Therefore, it is known that multifunctional NGCs fabricated through combinatorial approaches are needed to improve the functional and clinical outcomes after PNIs. The present work overviews the current reports dealing with the several features that can be used to improve peripheral nerve regeneration (PNR), ranging from the simple use of hollow NGCs to tissue engineered intraluminal fillers, or to even more advanced strategies, comprising the molecular and gene therapies as well as cell-based therapies.
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Affiliation(s)
- Cristiana R. Carvalho
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, Guimarães, Portugal
| | - Joaquim M. Oliveira
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, Guimarães, Portugal
| | - Rui L. Reis
- 3B's Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal
- ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, Guimarães, Portugal
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19
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Fu T, Lineaweaver WC, Zhang F, Zhang J. Role of shortwave and microwave diathermy in peripheral neuropathy. J Int Med Res 2019; 47:3569-3579. [PMID: 31304815 PMCID: PMC6726803 DOI: 10.1177/0300060519854905] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Objective This study was performed to review the current evidence for the efficacy of shortwave and microwave diathermy in promoting nerve regeneration after peripheral nerve injuries in both animal models and human patients. Methods An extensive literature search was conducted without publication data restrictions. Studies including the intervention and outcome in animal or human models were selected. Non-English studies, reviews, letters, and case reports were excluded. Results Eleven articles were included in this study. Shortwave diathermy at the frequency of 27.12 or 40.68 MHz was used in six of seven animal studies, while only one study utilized microwave diathermy at 915 MHz. Seven animal experiments demonstrated that shortwave or microwave diathermy produces an increased myelinated nerve fiber number, myelin sheath thickness, and axon diameter as well as improved electrophysiological parameters and locomotion. A total of 128 patients (207 wrists) were enrolled in four clinical studies. The clinical use of diathermy in human patients with carpal tunnel syndrome showed positive effects on pain, hand function, and electrophysiological findings. Conclusions Shortwave or microwave diathermy can improve the electrophysiological parameters, myelinated fiber number, and axon diameter of the injured nerve.
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Affiliation(s)
- Tengfei Fu
- 1 Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | | | - Feng Zhang
- 3 Division of Plastic Surgery, University of Mississippi Medical Center, Jackson, MS, USA
| | - Jian Zhang
- 1 Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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20
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Rink S, Bendella H, Akkin SM, Manthou M, Grosheva M, Angelov DN. Experimental Studies on Facial Nerve Regeneration. Anat Rec (Hoboken) 2019; 302:1287-1303. [DOI: 10.1002/ar.24123] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 10/09/2018] [Accepted: 11/02/2018] [Indexed: 12/20/2022]
Affiliation(s)
- Svenja Rink
- Department of Prosthetic Dentistry, School of Dental and Oral MedicineUniversity of Cologne Cologne Germany
| | - Habib Bendella
- Department of NeurosurgeryUniversity of Witten/Herdecke, Cologne Merheim Medical Center (CMMC) Cologne Germany
| | - Salih Murat Akkin
- Department of Anatomy, School of MedicineSANKO University Gaziantep Turkey
| | - Marilena Manthou
- Department of Histology and EmbryologyAristotle University Thessaloniki Thessaloniki Greece
| | - Maria Grosheva
- Department of Oto‐Rhino‐LaryngologyUniversity of Cologne Cologne Germany
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21
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Boecker A, Daeschler SC, Kneser U, Harhaus L. Relevance and Recent Developments of Chitosan in Peripheral Nerve Surgery. Front Cell Neurosci 2019; 13:104. [PMID: 31019452 PMCID: PMC6458244 DOI: 10.3389/fncel.2019.00104] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Accepted: 02/28/2019] [Indexed: 12/20/2022] Open
Abstract
Developments in tissue engineering yield biomaterials with different supporting strategies to promote nerve regeneration. One promising material is the naturally occurring chitin derivate chitosan. Chitosan has become increasingly important in various tissue engineering approaches for peripheral nerve reconstruction, as it has demonstrated its potential to interact with regeneration associated cells and the neural microenvironment, leading to improved axonal regeneration and less neuroma formation. Moreover, the physiological properties of its polysaccharide structure provide safe biodegradation behavior in the absence of negative side effects or toxic metabolites. Beneficial interactions with Schwann cells (SC), inducing differentiation of mesenchymal stromal cells to SC-like cells or creating supportive conditions during axonal recovery are only a small part of the effects of chitosan. As a result, an extensive body of literature addresses a variety of experimental strategies for the different types of nerve lesions. The different concepts include chitosan nanofibers, hydrogels, hollow nerve tubes, nerve conduits with an inner chitosan layer as well as hybrid architectures containing collagen or polyglycolic acid nerve conduits. Furthermore, various cell seeding concepts have been introduced in the preclinical setting. First translational concepts with hollow tubes following nerve surgery already transferred the promising experimental approach into clinical practice. However, conclusive analyses of the available data and the proposed impact on the recovery process following nerve surgery are currently lacking. This review aims to give an overview on the physiologic properties of chitosan, to evaluate its effect on peripheral nerve regeneration and discuss the future translation into clinical practice.
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Affiliation(s)
- A Boecker
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
| | - S C Daeschler
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
| | - U Kneser
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
| | - L Harhaus
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
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22
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Jia H, Wang Y, Chen J, Li JP, Han HQ, Tong XJ, He ZY, Ma WZ. Combination of BMSCs-laden acellular nerve xenografts transplantation and G-CSF administration promotes sciatic nerve regeneration. Synapse 2019; 73:e22093. [PMID: 30761618 DOI: 10.1002/syn.22093] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/03/2019] [Accepted: 02/11/2019] [Indexed: 12/12/2022]
Abstract
Peripheral nerve gaps often lead to interrupted innervation, manifesting as severe sensory and motor dysfunctions. The repairs of the nerve injuries have not achieved satisfactory curative effects in clinic. The transplantation of bone marrow stromal cells (BMSCs)-laden acellular nerve xenografts (ANX) has been proven more effective than the acellular nerve allografting. Besides, granulocyte colony-stimulating factor (G-CSF) can inhibit inflammation and apoptosis, and thus is conducive to the microenvironmental improvement of axonal regeneration. This study aims to investigate the joint effect of BMSCs-seeded ANX grafting and G-CSF administration, and explore the relevant mechanisms. Adult SD rats were divided into five groups randomly: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group, and autograft group. Eight weeks after transplantation, the detection of praxiology and neuroelectrophysiology was conducted, and then the morphology of the regenerated nerves was analyzed. The inflammatory response and apoptosis in the nerve grafts as well as the expression of the growth-promoting factors in the regenerated tissues were further assayed. G-CSF intervention and BMSCs implanting synergistically promoted peripheral nerve regeneration and functional recovery following ANX bridging, and the restoration effect was matchable with that of the autologous nerve grafting. Moreover, local inflammation was alleviated, the apoptosis of the seeded BMSCs was decreased, and the levels of the neuromodulatory factors were elevated. In conclusion, the union application of BMSCs-implanted ANX and G-CSF ameliorated the niche of neurotization and advanced nerve regeneration substantially. The strategy achieved the favorable effectiveness as an alternative to the autotransplantation.
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Affiliation(s)
- Hua Jia
- Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Ying Wang
- Research Institute of Neural Tissue Engineering, Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang, China
| | - Jiao Chen
- Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Jun-Ping Li
- Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Huai-Qin Han
- Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Xiao-Jie Tong
- Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China
| | - Zhong-Yi He
- Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - Wen-Zhi Ma
- Department of Human Anatomy and Histoembryology, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.,Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Key Laboratory of Reproduction and Genetics of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China
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23
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Ramli K, Aminath Gasim I, Ahmad AA, Hassan S, Law ZK, Tan GC, Baharuddin A, Naicker AS, Htwe O, Mohammed Haflah NH, B H Idrus R, Abdullah S, Ng MH. Human bone marrow-derived MSCs spontaneously express specific Schwann cell markers. Cell Biol Int 2019; 43:233-252. [PMID: 30362196 DOI: 10.1002/cbin.11067] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 10/07/2018] [Indexed: 12/15/2022]
Abstract
In peripheral nerve injuries, Schwann cells (SC) play pivotal roles in regenerating damaged nerve. However, the use of SC in clinical cell-based therapy is hampered due to its limited availability. In this study, we aim to evaluate the effectiveness of using an established induction protocol for human bone marrow derived-MSC (hBM-MSCs) transdifferentiation into a SC lineage. A relatively homogenous culture of hBM-MSCs was first established after serial passaging (P3), with profiles conforming to the minimal criteria set by International Society for Cellular Therapy (ISCT). The cultures (n = 3) were then subjected to a series of induction media containing β-mercaptoethanol, retinoic acid, and growth factors. Quantitative RT-PCR, flow cytometry, and immunocytochemistry analyses were performed to quantify the expression of specific SC markers, that is, S100, GFAP, MPZ and p75 NGFR, in both undifferentiated and transdifferentiated hBM-MSCs. Based on these analyses, all markers were expressed in undifferentiated hBM-MSCs and MPZ expression (mRNA transcripts) was consistently detected before and after transdifferentiation across all samples. There was upregulation at the transcript level of more than twofolds for NGF, MPB, GDNF, p75 NGFR post-transdifferentiation. This study highlights the existence of spontaneous expression of specific SC markers in cultured hBM-MSCs, inter-donor variability and that MSC transdifferentiation is a heterogenous process. These findings strongly oppose the use of a single marker to indicate SC fate. The heterogenous nature of MSC may influence the efficiency of SC transdifferentiation protocols. Therefore, there is an urgent need to re-define the MSC subpopulations and revise the minimal criteria for MSC identification.
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Affiliation(s)
- Khairunnisa Ramli
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Ifasha Aminath Gasim
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Amir Adham Ahmad
- Department of Orthopaedics, School of Medicine, International Medical University, Negeri Sembilan, Malaysia
| | - Shariful Hassan
- Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Zhe Kang Law
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Geok Chin Tan
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Azmi Baharuddin
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Amaramalar Selvi Naicker
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Ohnmar Htwe
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nor Hazla Mohammed Haflah
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Ruszymah B H Idrus
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Shalimar Abdullah
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Min Hwei Ng
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
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24
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Rodríguez Sánchez DN, de Lima Resende LA, Boff Araujo Pinto G, de Carvalho Bovolato AL, Possebon FS, Deffune E, Amorim RM. Canine Adipose-Derived Mesenchymal Stromal Cells Enhance Neuroregeneration in a Rat Model of Sciatic Nerve Crush Injury. Cell Transplant 2019; 28:47-54. [PMID: 30369261 PMCID: PMC6322136 DOI: 10.1177/0963689718809045] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 09/27/2018] [Accepted: 10/01/2018] [Indexed: 12/24/2022] Open
Abstract
Crush injuries in peripheral nerves are frequent and induce long-term disability with motor and sensory deficits. Due to axonal and myelin sheath disruptions, strategies for optimized axonal regeneration are needed. Multipotent mesenchymal stromal cells (MSC) are promising because of their anti-inflammatory properties and secretion of neurotrophins. The present study investigated the effect of canine adipose tissue MSC (Ad-MSC) transplantation in an experimental sciatic nerve crush injury. Wistar rats were divided into three groups: sham ( n = 8); Crush+PBS ( n = 8); Crush+MSC ( n = 8). Measurements of sciatic nerve functional index (SFI), muscle mass, and electromyography (EMG) were performed. Canine Ad-MSC showed mesodermal characteristics (CD34-, CD45-, CD44+, CD90+ and CD105+) and multipotentiality due to chondrogenic, adipogenic, and osteogenic differentiation. SFI during weeks 3 and 4 was significantly higher in the Crush+MSC group ( p < 0.001). During week 4, the EMG latency in the Crush+MSC groups had better near normality ( p < 0.05). The EMG amplitude showed results close to normality during week 4 in the Crush+MSC group ( p < 0.04). There were no statistical differences in muscle weight between the groups ( p > 0.05), but there was a tendency toward weight gain in the Crush+MSC groups. Better motor functional recovery after crush and perineural canine Ad-MSC transplantation was observed during week 2. This was maintained till week 4. In conclusion, the canine Ad-MSC transplantation showed early pro-regenerative effects between 2-4 weeks in the rat model of sciatic nerve crush injury.
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Affiliation(s)
- Diego Noé Rodríguez Sánchez
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), São Paulo, Brazil
- Blood Transfusion Center, Cell Engineering Laboratory, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Luiz Antonio de Lima Resende
- Department of Neurology and Psychiatry, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Giovana Boff Araujo Pinto
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), São Paulo, Brazil
- Blood Transfusion Center, Cell Engineering Laboratory, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Ana Lívia de Carvalho Bovolato
- Blood Transfusion Center, Cell Engineering Laboratory, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Fábio Sossai Possebon
- Department of Veterinary Hygiene and Public Health, College of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), São Paulo, Brazil
| | - Elenice Deffune
- Blood Transfusion Center, Cell Engineering Laboratory, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Rogério Martins Amorim
- Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), São Paulo, Brazil
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25
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Petrova ES. Differentiation Potential of Mesenchymal Stem Cells and Stimulation of Nerve Regeneration. Russ J Dev Biol 2018. [DOI: 10.1134/s1062360418040033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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26
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Li Y, Yu Z, Men Y, Chen X, Wang B. Laminin-chitosan-PLGA conduit co-transplanted with Schwann and neural stem cells to repair the injured recurrent laryngeal nerve. Exp Ther Med 2018; 16:1250-1258. [PMID: 30116376 PMCID: PMC6090254 DOI: 10.3892/etm.2018.6343] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Accepted: 03/10/2017] [Indexed: 12/23/2022] Open
Abstract
The aim of the present study was to assess the possibility and efficacy of utilizing a laminin-chitosan-poly (lactic-co-glycolic acid), otherwise known as laminin-chitosan-PLGA, nerve conduit with the co-transplantation of Schwann and neural stem cells to repair peripheral nerve defects. Previous in vitro experiments have demonstrated that the three-dimensional structure of the built in fiber filament electrospinning of laminin-chitosan-PLGA nerve conduit is beneficial to the migration and regeneration of nerve cells, and has notable mechanical strength and plasticity. It is able to provide support in the neural tissue regeneration process, and has the ability to degrade itself once peripheral nerves complete their regeneration, providing more advantages than other biological and synthetic materials. In the present study, 132 female Sprague Dawley rats were used to establish an animal model of laryngeal nerve injury, and the rats were randomly divided into six groups for experimentation. The nerve conduit was prepared and co-cultured with Schwann and neural stem cells, and micro-surgical techniques were used to repair the 5-mm-long recurrent laryngeal nerve injuries. Functional and histological assessments were performed at 8 and 12 weeks post-surgery, respectively. The results revealed that the laminin-chitosan-PLGA nerve conduit combined with Schwann and neural stem cells was able to promote nerve regeneration (P<0.05), and its effect was superior to those of the autograft (P<0.05). The results of the present study suggest that this is the ideal method for repairing peripheral nerve defects, and cells in the graft may promote nerve regeneration.
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Affiliation(s)
- Yu Li
- Department of Otolaryngology, Head and Neck Surgery, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200000, P.R. China
| | - Ziwei Yu
- Department of Otolaryngology, Head and Neck Surgery, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200000, P.R. China
| | - Yongzhi Men
- Department of Otolaryngology, Head and Neck Surgery, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200000, P.R. China
| | - Xinwei Chen
- Department of Otolaryngology, Head and Neck Surgery, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200000, P.R. China
| | - Baoxin Wang
- Department of Otolaryngology, Head and Neck Surgery, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200000, P.R. China
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27
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Bucan V, Vaslaitis D, Peck CT, Strauß S, Vogt PM, Radtke C. Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury. Mol Neurobiol 2018; 56:1812-1824. [PMID: 29931510 PMCID: PMC6394792 DOI: 10.1007/s12035-018-1172-z] [Citation(s) in RCA: 170] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 06/01/2018] [Indexed: 12/29/2022]
Abstract
Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the microenvironment provided by nerve conduit remains unclear. In this study, we evaluate the effects of from adipose-derived mesenchymal stem cells (adMSCs) originating exosomes with respect to sciatic nerve regeneration and neurite growth. Molecular and immunohistochemical techniques were used to investigate the presence of characteristic exosome markers. A co-culture system was established to determine the effect of exosomes on neurite elongation in vitro. The in vivo walking behaviour of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by immunocytochemistry. adMSCs secrete nano-vesicles known as exosomes, which increase neurite outgrowth in vitro and enhance regeneration after sciatic nerve injury in vivo. Furthermore, we showed the presence of neural growth factors transcripts in adMSC exosomes for the first time. Our results demonstrate that exosomes, constitutively produced by adMSCs, are involved in peripheral nerve regeneration and have the potential to be utilised as a therapeutic tool for effective tissue-engineered nerves.
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Affiliation(s)
- Vesna Bucan
- Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. .,Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Feodor-Lynen Str. 21, Hannover, Germany.
| | - Desiree Vaslaitis
- Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.,Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Feodor-Lynen Str. 21, Hannover, Germany
| | - Claas-Tido Peck
- Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.,Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Feodor-Lynen Str. 21, Hannover, Germany
| | - Sarah Strauß
- Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.,Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Feodor-Lynen Str. 21, Hannover, Germany
| | - Peter M Vogt
- Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.,Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Feodor-Lynen Str. 21, Hannover, Germany
| | - Christine Radtke
- Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.,Department of Plastic and Reconstructive Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
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28
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Behkami S, Frounchi J, Ghaderi Pakdel F, Stieglitz T. Simulation of effects of the electrode structure and material in the density measuring system of the peripheral nerve based on micro-electrical impedance tomography. BIOMED ENG-BIOMED TE 2018; 63:151-161. [PMID: 28076294 DOI: 10.1515/bmt-2016-0089] [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] [Received: 04/11/2016] [Accepted: 11/28/2016] [Indexed: 12/20/2022]
Abstract
The electrode structure in micro-electrical impedance tomography (MEIT) highly influences the measurement sensitivity and therefore the reconstructed image quality. Hence, optimizing the electrode structure leads to the improvement of image quality in the reconstruction procedure. Although there have been many investigations on electrical impedance tomography (EIT) electrodes, there is no comprehensive study on their influence on images of the peripheral nerve. In this paper, we present a simulation method to study the effects of the electrode structure in the density measurement system of the peripheral nerve based on MEIT. The influence of the electrode structure such as dimensions, material and the number of electrodes and also the recognition feature of different radii of fascicle and different locations of fascicles has been studied. Data were reconstructed from the real and imaginary parts of complex conductivity data, respectively. It has been shown that the material of the electrodes had no effect on the reconstructed images, while the dimensions of the electrodes significantly affected the image sensitivity and thus the image quality. An increase in the number of electrodes increased the amount of data and information content. However, as the number of electrodes increased due to the given perimeter of the peripheral nerve, the area of the electrodes was reduced. This reduction affects the reconstructed image quality. The real and imaginary parts of the data were separately reconstructed for each case. Although, in real EIT systems, the reconstructed images using the real part of the signal have a better signal-to-noise ratio (SNR), this study proved that for a density measuring system of the peripheral nerve, the reconstructed images using the imaginary part of the signal had better quality. This simulation study proposes the effects of the electrode size and material and obtained spatial resolution that was high enough to reconstruct fascicles in a peripheral nerve.
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Affiliation(s)
- Saber Behkami
- Microelectronic and Microsensor Laboratory, Department of Electrical Engineering, Faculty of Electrical and Computer Engineering, Tabriz University, Tabriz, East Azerbaijan, Iran
| | - Javad Frounchi
- Department of Electrical Engineering, Faculty of Electrical and Computer Engineering, Tabriz University, Tabriz, East Azerbaijan, Iran
| | - Firouz Ghaderi Pakdel
- Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, West Azerbaijan, Iran
| | - Thomas Stieglitz
- Department of Microsystems Engineering (IMTEK), University of Freiburg, Georges-Koehler-Allee 106, Freiburg 79110, Germany
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29
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Prest TA, Yeager E, LoPresti ST, Zygelyte E, Martin MJ, Dong L, Gibson A, Olutoye OO, Brown BN, Cheetham J. Nerve-specific, xenogeneic extracellular matrix hydrogel promotes recovery following peripheral nerve injury. J Biomed Mater Res A 2018; 106:450-459. [PMID: 28891122 PMCID: PMC5745279 DOI: 10.1002/jbm.a.36235] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Revised: 08/16/2017] [Accepted: 09/08/2017] [Indexed: 01/07/2023]
Abstract
Peripheral nerve possesses the inherent ability to regrow and recover following injury. However, nerve regeneration is often slow and incomplete due to limitations associated with the local microenvironment during the repair process. Manipulation of the local microenvironment at the site of nerve repair, therefore, represents a significant opportunity for improvement in downstream outcomes. Macrophages and Schwann cells play a key role in the orchestration of early events after peripheral nerve injury. We describe the production, characterization, and use of an injectable, peripheral nerve-specific extracellular matrix-based hydrogel (PNSECM) for promoting modulation of the local macrophage and Schwann cell responses at the site of nerve repair in a rodent model of sciatic nerve injury. We show that PNSECM hydrogels largely maintain the matrix structure associated with normal native peripheral nerve tissue. PNSECM hydrogels were also found to promote increased macrophage invasion, higher percentages of M2 macrophages and enhanced Schwann cell migration when used as a lumen filler in a rodent model of nerve gap repair using an inert nerve guidance conduit. These results suggest that an injectable PNSECM hydrogel can provide a supportive, bioactive scaffold which promotes repair of peripheral nerve in vivo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 450-459, 2018.
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Affiliation(s)
- Travis A. Prest
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
| | - Eric Yeager
- Department of Clinical Sciences, Cornell University, Ithaca, NY
| | - Samuel T. LoPresti
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
| | | | | | - Longying Dong
- Department of Clinical Sciences, Cornell University, Ithaca, NY
| | - Alexis Gibson
- Department of Clinical Sciences, Cornell University, Ithaca, NY
| | - Oluyinka O. Olutoye
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
| | - Bryan N. Brown
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA
- Department of Clinical Sciences, Cornell University, Ithaca, NY
| | - Jonathan Cheetham
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA
- Department of Clinical Sciences, Cornell University, Ithaca, NY
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30
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Kim JI, Kim CS, Park CH. Harnessing Nanotopography of Electrospun Nanofibrous Nerve Guide Conduits (NGCs) for Neural Tissue Engineering. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1078:395-408. [PMID: 30357634 DOI: 10.1007/978-981-13-0950-2_20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The anatomical recovery of nerve defects with their neurological functions after an injury caused by diseases or accidents is an important clinical issue. The most efficient surgical technique so far to the nerve defects, which are unrepairable by direct end-to-end suture, can be autograft transplantation. The autograft transplantation, however, has disadvantages including multiple rounds of surgery, a shortage of nerve donor, and function loss at the donor site. Tissue-engineered nerve guide conduits (TENGCs) have emerged as a potential alternative to autologous nerve grafts for nerve regeneration and functional recovery. Various TENGCs researches are being carried out to improve characteristics and enhance functionality such as material selection, biomimetic, topography, and enhancement by the biomolecules additions. Among them, the customizable surface nanotopography of aligned fibrous TENGCs foster neural repair by providing a cell-friendly environment, permissiveness, guidance cues, and directional growth of the cells. Fibrous nerve guide conduits (NGCs) made of longitudinally ordered fibers is a promising candidate for nerve tissue engineering.
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Affiliation(s)
- Jeong In Kim
- Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju, South Korea
| | - Cheol Sang Kim
- Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju, South Korea. .,Division of Mechanical Design Engineering, College of Engineering, Chonbuk National University, Jeonju, South Korea.
| | - Chan Hee Park
- Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju, South Korea. .,Division of Mechanical Design Engineering, College of Engineering, Chonbuk National University, Jeonju, South Korea.
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31
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De la Rosa MB, Kozik EM, Sakaguchi DS. Adult Stem Cell-Based Strategies for Peripheral Nerve Regeneration. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1119:41-71. [PMID: 30151648 DOI: 10.1007/5584_2018_254] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Peripheral nerve injuries (PNI) occur as the result of sudden trauma and can lead to life-long disability, reduced quality of life, and heavy economic and social burdens. Although the peripheral nervous system (PNS) has the intrinsic capacity to regenerate and regrow axons to a certain extent, current treatments frequently show incomplete recovery with poor functional outcomes, particularly for large PNI. Many surgical procedures are available to halt the propagation of nerve damage, and the choice of a procedure depends on the extent of the injury. In particular, recovery from large PNI gaps is difficult to achieve without any therapeutic intervention or some form of tissue/cell-based therapy. Autologous nerve grafting, considered the "gold standard" is often implemented for treatment of gap formation type PNI. Although these surgical procedures provide many benefits, there are still considerable limitations associated with such procedures as donor site morbidity, neuroma formation, fascicle mismatch, and scarring. To overcome such restrictions, researchers have explored various avenues to improve post-surgical outcomes. The most commonly studied methods include: cell transplantation, growth factor delivery to stimulate regenerating axons and implanting nerve guidance conduits containing replacement cells at the site of injury. Replacement cells which offer maximum benefits for the treatment of PNI, are Schwann cells (SCs), which are the peripheral glial cells and in part responsible for clearing out debris from the site of injury. Additionally, they release growth factors to stimulate myelination and axonal regeneration. Both primary SCs and genetically modified SCs enhance nerve regeneration in animal models; however, there is no good source for extracting SCs and the only method to obtain SCs is by sacrificing a healthy nerve. To overcome such challenges, various cell types have been investigated and reported to enhance nerve regeneration.In this review, we have focused on cell-based strategies aimed to enhance peripheral nerve regeneration, in particular the use of mesenchymal stem cells (MSCs). Mesenchymal stem cells are preferred due to benefits such as autologous transplantation, routine isolation procedures, and paracrine and immunomodulatory properties. Mesenchymal stem cells have been transplanted at the site of injury either directly in their native form (undifferentiated) or in a SC-like form (transdifferentiated) and have been shown to significantly enhance nerve regeneration. In addition to transdifferentiated MSCs, some studies have also transplanted ex-vivo genetically modified MSCs that hypersecrete growth factors to improve neuroregeneration.
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Affiliation(s)
- Metzere Bierlein De la Rosa
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.,Veterinary Specialty Center, Buffalo Grove, IL, USA
| | - Emily M Kozik
- Biology Program, Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA, USA.,Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA, USA
| | - Donald S Sakaguchi
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA. .,Biology Program, Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA, USA. .,Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA, USA. .,Neuroscience Program, Iowa State University, Ames, IA, USA.
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Seo N, Lee SH, Ju KW, Woo J, Kim B, Kim S, Jahng JW, Lee JH. Low-frequency pulsed electromagnetic field pretreated bone marrow-derived mesenchymal stem cells promote the regeneration of crush-injured rat mental nerve. Neural Regen Res 2018; 13:145-153. [PMID: 29451219 PMCID: PMC5840980 DOI: 10.4103/1673-5374.224383] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to promote the regeneration of injured peripheral nerves. Pulsed electromagnetic field (PEMF) reportedly promotes the proliferation and neuronal differentiation of BMSCs. Low-frequency PEMF can induce the neuronal differentiation of BMSCs in the absence of nerve growth factors. This study was designed to investigate the effects of low-frequency PEMF pretreatment on the proliferation and function of BMSCs and the effects of low-frequency PEMF pre-treated BMSCs on the regeneration of injured peripheral nerve using in vitro and in vivo experiments. In in vitro experiments, quantitative DNA analysis was performed to determine the proliferation of BMSCs, and reverse transcription-polymerase chain reaction was performed to detect S100 (Schwann cell marker), glial fibrillary acidic protein (astrocyte marker), and brain-derived neurotrophic factor and nerve growth factor (neurotrophic factors) mRNA expression. In the in vivo experiments, rat models of crush-injured mental nerve established using clamp method were randomly injected with low-frequency PEMF pretreated BMSCs, unpretreated BMSCs or PBS at the injury site (1 × 106 cells). DiI-labeled BMSCs injected at the injury site were counted under the fluorescence microscope to determine cell survival. One or two weeks after cell injection, functional recovery of the injured nerve was assessed using the sensory test with von Frey filaments. Two weeks after cell injection, axonal regeneration was evaluated using histomorphometric analysis and retrograde labeling of trigeminal ganglion neurons. In vitro experiment results revealed that low-frequency PEMF pretreated BMSCs proliferated faster and had greater mRNA expression of growth factors than unpretreated BMSCs. In vivo experiment results revealed that compared with injection of unpretreated BMSCs, injection of low-frequency PEMF pretreated BMSCs led to higher myelinated axon count and axon density and more DiI-labeled neurons in the trigeminal ganglia, contributing to rapider functional recovery of injured mental nerve. These findings suggest that low-frequency PEMF pretreatment is a promising approach to enhance the efficacy of cell therapy for peripheral nerve injury repair.
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Affiliation(s)
- NaRi Seo
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Seoul National University; Dental Research Institute, Seoul National University, Seoul, South Korea
| | - Sung-Ho Lee
- Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital; Dental Research Institute, Seoul National University, Seoul, South Korea
| | - Kyung Won Ju
- Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital; Dental Research Institute, Seoul National University, Seoul, South Korea
| | - JaeMan Woo
- Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, Seoul, South Korea
| | - BongJu Kim
- Clinical Translational Research Center for Dental Science (CTRC), Seoul National University Dental Hospital, Seoul, South Korea
| | - SoungMin Kim
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Seoul National University; Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, Seoul, South Korea
| | - Jeong Won Jahng
- Dental Research Institute, Seoul National University, Seoul, South Korea
| | - Jong-Ho Lee
- Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Seoul National University; Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital; Dental Research Institute, Seoul National University; Clinical Translational Research Center for Dental Science (CTRC), Seoul National University Dental Hospital, Seoul, South Korea
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Suchyta MA, Sabbagh MD, Morsy M, Mardini S, Moran SL. Advances in peripheral nerve regeneration as it relates to VCA. ACTA ACUST UNITED AC 2017. [DOI: 10.1080/23723505.2017.1344347] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
| | - M. Diya Sabbagh
- Department of Plastic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Mohamed Morsy
- Department of Plastic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Orthopedic Surgery, Assiut University Hospital, Assiut University, Assiut, Egypt
| | - Samir Mardini
- Department of Plastic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Steven L. Moran
- Department of Plastic Surgery, Mayo Clinic, Rochester, MN, USA
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Systemic Transplantation of Bone Marrow Mononuclear Cells Promotes Axonal Regeneration and Analgesia in a Model of Wallerian Degeneration. Transplantation 2017; 101:1573-1586. [DOI: 10.1097/tp.0000000000001478] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Zhao Z, Li X, Li Q. Curcumin accelerates the repair of sciatic nerve injury in rats through reducing Schwann cells apoptosis and promoting myelinization. Biomed Pharmacother 2017. [PMID: 28622711 DOI: 10.1016/j.biopha.2017.05.099] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. OBJECTIVE The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. METHODS After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days. The phosphorylation of Erk1/2 and Akt, and the expression of LC3-II, Beclin 1 and p62 were measured using western blotting. After treatment for 60days, myelination of the injured sciatic nerve was evaluated by MBP immunohistochemical staining and the expression of PMP22, Fibrin and S100 were determined using qRT-PCR and western blotting. In vitro, RSC96 cells were starved for 12h to induce autophagy, and received DMSO, curcumin, PD98059+curcumin, IGF-1+curcumin and BFA1 respectively. The phosphorylation of Erk1/2、Akt and the expression of LC3-II, Beclin 1, p62, PMP22, Fibrin and S100 were measured using western blotting, and the cell apoptosis was detected by flow cytometry. RESULTS Curcumin could promote injury-induced cell autophagy, remyelination and axon regeneration in sciatic nerve of rats. In vitro, curcumin could accelerate cell autophagy through regulating autophagy related Erk1/2 and Akt pathway, prevent cell apoptosis and promote expression of PMP22 and S100, and reduced deposition of Fibrin in cultured RSC96 SCs. CONCLUSIONS Curcumin could accelerate injured sciatic nerve repair in rats through reducing SCs apoptosis and promoting myelinization.
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Affiliation(s)
- Zhiwei Zhao
- Luoyang Orthopedic Hospital of Henan Province, Zhengzhou 450046, Henan Province, China
| | - Xiaoling Li
- Luoyang Orthopedic Hospital of Henan Province, Zhengzhou 450046, Henan Province, China.
| | - Qing Li
- Department of Orthopaedics, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming 650032, Yunnan Province, China.
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Zheng M, Duan J, He Z, Wang Z, Mu S, Zeng Z, Qu J, Wang D, Zhang J. Transplantation of bone marrow stromal stem cells overexpressing tropomyosin receptor kinase A for peripheral nerve repair. Cytotherapy 2017; 19:916-926. [PMID: 28571657 DOI: 10.1016/j.jcyt.2017.04.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 03/28/2017] [Accepted: 04/24/2017] [Indexed: 01/19/2023]
Abstract
BACKGROUND AIMS Previously we reported that overexpression of tropomyosin receptor kinase A (TrkA) could improve the survival and Schwann-like cell differentiation of bone marrow stromal stem cells (BMSCs) in nerve grafts for bridging rat sciatic nerve defects. The aim of this study was to investigate how TrkA affects the efficacy of BMSCs transplantation on peripheral nerve regeneration and functional recovery. METHODS Rat BMSCs were infected with recombinant lentiviruses to construct TrkA-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then seeded in acellular nerve allografts for bridging 10-mm rat sciatic nerve defects. RESULTS At 8 weeks post-transplantation, compared with Vector and Control BMSCs-laden groups, TrkA-overexpressing BMSCs-laden group demonstrated obviously improved axon growth, such as significantly higher expression of myelin basic protein and superior results of myelinated fiber density, axon diameter and myelin sheaths thickness. In accordance with this increased nerve regeneration, the animals of TrkA-overexpressing BMSCs-laden group showed significantly better restoration of sciatic nerve function, manifested as greater sciatic function index value and superior electrophysiological parameters including shorter onset latency and higher peak amplitude of compound motor action potentials and faster nerve conduction velocity. However, these beneficial effects could be reversed in TrkA-shRNA-expressing BMSCs-laden group, which showed much fewer and smaller axons with thinner myelin sheaths and correspondingly poor functional recovery. CONCLUSIONS These results demonstrated that TrkA may regulate the regenerative potential of BMSCs in nerve grafts, and TrkA overexpression can enhance the efficacy of BMSCs on peripheral nerve regeneration and functional recovery, which may help establish novel strategies for repairing peripheral nerve injuries.
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Affiliation(s)
- Meige Zheng
- Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China; School of Medicine, Shenzhen University, Shenzhen, China
| | - Junxiu Duan
- School of Medicine, Shenzhen University, Shenzhen, China
| | - Zhendan He
- School of Medicine, Shenzhen University, Shenzhen, China
| | - Zhiwei Wang
- Department of Neurology, Shenzhen Shekou people's Hospital, Shenzhen, China
| | - Shuhua Mu
- Psychology & Social College of Shenzhen University, Shenzhen, China
| | - Zhiwen Zeng
- School of Medicine, Shenzhen University, Shenzhen, China
| | - Junle Qu
- Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China
| | - Dong Wang
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, China.
| | - Jian Zhang
- School of Medicine, Shenzhen University, Shenzhen, China.
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Human eyelid adipose tissue-derived Schwann cells promote regeneration of a transected sciatic nerve. Sci Rep 2017; 7:43248. [PMID: 28256528 PMCID: PMC5335702 DOI: 10.1038/srep43248] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 01/23/2017] [Indexed: 01/16/2023] Open
Abstract
Schwann cells (SCs) can promote the regeneration of injured peripheral nerves while the clinical application is limited by donor site complications and the inability to generate an ample amount of cells. In this study, we have isolated human eyelid adipose-derived Schwann cells (hE-SCs) from human eyelid adipose tissue and identified the cell phenotype and function. Using immunofluorescence and H & E staining, we detected subtle nerve fibers and SCs in human eyelid adipose tissue. Immunofluorescence staining indicated that hE-SCs expressed glial markers, such as S100, p75NTR GFAP, Sox10 and Krox20. To explore whether hE-SCs promote the regeneration of injured peripheral nerves in vivo, a Balb/c-nu mice model was used in the study, and mice were randomly assigned to five groups: Matrigel; hE-SCs/P0; hE-SCs/P2; hE-FLCs/P2; and Autograft. After 12 weeks, functional and histological assessments of the regenerated nerves showed that sciatic nerve defect was more effectively repaired in the hE-SCs/P2 group which achieved 66.1 ± 6.5% purity, than the other three groups and recovered to similar level to the Autograft group. These results indicated that hE-SCs can promote the regeneration of injured peripheral nerve and the abundant, easily accessible supply of adipose tissue might be a promising source of SCs for peripheral nerve repair.
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Carnevale G, Pisciotta A, Riccio M, Bertoni L, De Biasi S, Gibellini L, Zordani A, Cavallini GM, La Sala GB, Bruzzesi G, Ferrari A, Cossarizza A, de Pol A. Human dental pulp stem cells expressing STRO-1, c-kit and CD34 markers in peripheral nerve regeneration. J Tissue Eng Regen Med 2017; 12:e774-e785. [PMID: 27943583 DOI: 10.1002/term.2378] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Revised: 10/10/2016] [Accepted: 12/06/2016] [Indexed: 12/16/2022]
Abstract
Peripheral nerve injuries are a commonly encountered clinical problem and often result in long-term functional defects. The application of stem cells able to differentiate in Schwann cell-like cells in vitro and in vivo, could represent an attractive therapeutic approach for the treatment of nerve injuries. Further, stem cells sources sharing the same embryological origin as Schwann cells might be considered a suitable tool. The aim of this study was to demonstrate the ability of a neuroectodermal subpopulation of human STRO-1+ /c-Kit+ /CD34+ DPSCs, expressing P75NTR , nestin and SOX-10, to differentiate into Schwann cell-like cells in vitro and to promote axonal regeneration in vivo, which led to functional recovery as measured by sustained gait improvement, in animal rat model of peripheral nerve injury. Transplanted human dental pulp stem cells (hDPSCs) engrafted into sciatic nerve defect, as revealed by the positive staining against human nuclei, showed the expression of typical Schwann cells markers, S100b and, noteworthy, a significant number of myelinated axons was detected. Moreover, hDPSCs promoted axonal regeneration from proximal to distal stumps 1 month after transplantation. This study demonstrates that STRO-1+ /c-Kit+ /CD34+ hDPSCs, associated with neural crest derivation, represent a promising source of stem cells for the treatment of demyelinating disorders and might provide a valid alternative tool for future clinical applications to achieve functional recovery after injury or peripheral neuropathies besides minimizing ethical issues. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Gianluca Carnevale
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandra Pisciotta
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Massimo Riccio
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Laura Bertoni
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Sara De Biasi
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Lara Gibellini
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessio Zordani
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Gian Maria Cavallini
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | | | - Giacomo Bruzzesi
- Oro-Maxillo-Facial Department, AUSL Baggiovara, Baggiovara, Modena, Italy
| | - Adriano Ferrari
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.,Children Rehabilitation Special Unit, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
| | - Andrea Cossarizza
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Anto de Pol
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
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Zheng M, Duan J, He Z, Wang Z, Mu S, Zeng Z, Qu J, Zhang J, Wang D. Overexpression of tropomyosin receptor kinase A improves the survival and Schwann-like cell differentiation of bone marrow stromal cells in nerve grafts for bridging rat sciatic nerve defects. Cytotherapy 2016; 18:1256-69. [PMID: 27497699 DOI: 10.1016/j.jcyt.2016.06.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 06/28/2016] [Indexed: 01/19/2023]
Abstract
BACKGROUND AIMS Bone marrow stromal cells (BMSCs) can differentiate into Schwann-like cells in vivo and effectively promote nerve regeneration and functional recovery as the seed cells for peripheral nerve repair. However, the survival rate and neural differentiation rate of the transplanted BMSCs are very low, which would limit their efficacy. METHODS In this work, rat BMSCs were infected by recombinant lentiviruses to construct tropomyosin receptor kinase A (TrkA)-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then used in transplantation for rat sciatic nerve defects. RESULTS We showed that lentivirus-mediated overexpression of TrkA in BMSCs can promote cell survival and protect against serum-starve-induced apoptosis in vitro. At 8 weeks after transplantation, the Schwann-like differentiated ratio of the existing implanted cells had reached 74.8 ± 1.6% in TrkA-overexpressing BMSCs-laden nerve grafts, while 40.7 ± 2.3% and 42.3 ± 1.5% in vector and control BMSCs-laden nerve grafts, but only 8.2 ± 1.8% in TrkA-shRNA-expressing BMSCs-laden nerve grafts. The cell apoptosis ratio of the existing implanted cells in TrkA-overexpressing BMSCs-laden nerve grafts was 16.5 ± 1.2%, while 33.9 ± 1.9% and 42.6 ± 2.9% in vector and control BMSCs-laden nerve grafts, but 87.2 ± 2.5% in TrkA-shRNA-expressing BMSCs-laden nerve grafts. CONCLUSIONS These results demonstrate that TrkA overexpression can improve the survival and Schwann-like cell differentiation of BMSCs and prevent cell death in nerve grafts, which may have potential implication in advancing cell transplantation for peripheral nerve repair.
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Affiliation(s)
- Meige Zheng
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, China; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China
| | - Junxiu Duan
- School of Medicine, Shenzhen University, Shenzhen, China
| | - Zhendan He
- School of Medicine, Shenzhen University, Shenzhen, China
| | - Zhiwei Wang
- Department of Neurology, Shenzhen Shekou People's Hospital, Shenzhen, China
| | - Shuhua Mu
- Psychology & Social College, Shenzhen University, Shenzhen, China
| | - Zhiwen Zeng
- School of Medicine, Shenzhen University, Shenzhen, China
| | - Junle Qu
- Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China
| | - Jian Zhang
- School of Medicine, Shenzhen University, Shenzhen, China.
| | - Dong Wang
- Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, China.
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Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue–Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration–Approved Nerve Conduit. Plast Reconstr Surg 2016; 138:132-139. [DOI: 10.1097/prs.0000000000002291] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Liu Y, Chen J, Liu W, Lu X, Liu Z, Zhao X, Li G, Chen Z. A Modified Approach to Inducing Bone Marrow Stromal Cells to Differentiate into Cells with Mature Schwann Cell Phenotypes. Stem Cells Dev 2016; 25:347-59. [PMID: 26670188 DOI: 10.1089/scd.2015.0295] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Marrow stromal cells (MSCs) can be induced to differentiate into Schwann-like cells under classical induction conditions. However, cells derived from this method are unstable, exhibiting a low neurotrophin expression level after the induction conditions are removed. In Schwann cell (SC) culture, progesterone (PROG) enhances neurotrophic synthesis and myelination, specifically regulating the expression of the myelin protein zero (P0)- and peripheral myelin protein 22 (PMP22)-encoding genes by acting in concert or in synergy with insulin and glucocorticoids (GLUCs). In the present study, we investigated whether combined PROG, GLUC, and insulin therapy induced MSCs to differentiate into modified SC-like cells with phenotypes similar to those of mature SCs. After being cultured for 2 weeks in modified differentiation medium, the modified SC-like cells showed increased expression of P0 and PMP22. In addition, morphological and phenotypic characterizations were conducted over a period of over 2 weeks, and functional characteristics persisted for more than 3 weeks after the induction reagents were withdrawn. The transplantation of green fluorescent protein-labeled, modified SC-like cells into transected sciatic nerves with a 10-mm gap significantly increased the proliferation of the original SCs and improved axon regeneration and myelination compared with original BM-SCs. Immunostaining for P0 revealed that more of the transplanted modified SC-like cells retained the phenotypic characteristics of SCs. Taken together, these results reveal that the combined application of PROG, GLUC, and insulin induces MSCs to differentiate into cells with phenotypic, molecular, and functional properties of mature SCs.
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Affiliation(s)
- Yutian Liu
- 1 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Jianghai Chen
- 1 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Wei Liu
- 2 Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Xiaocheng Lu
- 1 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Zhenyu Liu
- 1 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Xiaobo Zhao
- 1 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Gongchi Li
- 1 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Zhenbing Chen
- 1 Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
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Abstract
Tissue engineering of Schwann cells (SCs) can serve a number of purposes, such as in vitro SC-related disease modeling, treatment of peripheral nerve diseases or peripheral nerve injury, and, potentially, treatment of CNS diseases. SCs can be generated from autologous stem cells in vitro by recapitulating the various stages of in vivo neural crest formation and SC differentiation. In this review, we survey the cellular and molecular mechanisms underlying these in vivo processes. We then focus on the current in vitro strategies for generating SCs from two sources of pluripotent stem cells, namely embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Different methods for SC engineering from ESCs and iPSCs are reviewed and suggestions are proposed for optimizing the existing protocols. Potential safety issues regarding the clinical application of iPSC-derived SCs are discussed as well. Lastly, we will address future aspects of SC engineering.
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PERIPHERAL NERVE REGENERATION: CELL THERAPY AND NEUROTROPHIC FACTORS. Rev Bras Ortop 2015; 46:643-9. [PMID: 27027067 PMCID: PMC4799329 DOI: 10.1016/s2255-4971(15)30319-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2011] [Accepted: 06/16/2011] [Indexed: 12/25/2022] Open
Abstract
Peripheral nerve trauma results in functional loss in the innervated organ, and recovery without surgical intervention is rare. Many surgical techniques can be used for nerve repair. Among these, the tubulization technique can be highlighted: this allows regenerative factors to be introduced into the chamber. Cell therapy and tissue engineering have arisen as an alternative for stimulating and aiding peripheral nerve regeneration. Therefore, the aim of this review was to provide a survey and analysis on the results from experimental and clinical studies that used cell therapy and tissue engineering as tools for optimizing the regeneration process. The articles used came from the LILACS, Medline and SciELO scientific databases. Articles on the use of stem cells, Schwann cells, growth factors, collagen, laminin and platelet-rich plasma for peripheral nerve repair were summarized over the course of the review. Based on these studies, it could be concluded that the use of stem cells derived from different sources presents promising results relating to nerve regeneration, because these cells have a capacity for neuronal differentiation, thus demonstrating effective functional results. The use of tubes containing bioactive elements with controlled release also optimizes the nerve repair, thus promoting greater myelination and axonal growth of peripheral nerves. Another promising treatment is the use of platelet-rich plasma, which not only releases growth factors that are important in nerve repair, but also serves as a carrier for exogenous factors, thereby stimulating the proliferation of specific cells for peripheral nerve repair.
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Boecker AH, van Neerven SGA, Scheffel J, Tank J, Altinova H, Seidensticker K, Deumens R, Tolba R, Weis J, Brook GA, Pallua N, Bozkurt A. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model. Eur J Neurosci 2015; 43:404-16. [DOI: 10.1111/ejn.13052] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Revised: 08/13/2015] [Accepted: 08/14/2015] [Indexed: 11/30/2022]
Affiliation(s)
- Arne Hendrik Boecker
- Department of Plastic Surgery, Reconstructive and Hand Surgery; Burn Center; University Hospital RWTH Aachen; Pauwelsstrasse 30 52074 Aachen Germany
| | - Sabien Geraldine Antonia van Neerven
- Department of Plastic Surgery, Reconstructive and Hand Surgery; Burn Center; University Hospital RWTH Aachen; Pauwelsstrasse 30 52074 Aachen Germany
| | - Juliane Scheffel
- Department of Plastic Surgery, Reconstructive and Hand Surgery; Burn Center; University Hospital RWTH Aachen; Pauwelsstrasse 30 52074 Aachen Germany
| | - Julian Tank
- Department of Plastic Surgery, Reconstructive and Hand Surgery; Burn Center; University Hospital RWTH Aachen; Pauwelsstrasse 30 52074 Aachen Germany
| | - Haktan Altinova
- Institute of Neuropathology; University Hospital RWTH Aachen; Aachen Germany
- Department of Neurosurgery; Evangelic Hospital Bethel; Bielefeld Germany
| | - Katrin Seidensticker
- M.A.R.C.O. GmbH & Co. KG; Institute for Clinical Research and Statistics; Düsseldorf Germany
| | - Ronald Deumens
- Institute of Neuropathology; University Hospital RWTH Aachen; Aachen Germany
- Neuropharmacology; Université Catholique de Louvain; Brussels Belgium
| | - Rene Tolba
- Institute for Laboratory Animal Research; University Hospital RWTH Aachen; Aachen Germany
| | - Joachim Weis
- Institute of Neuropathology; University Hospital RWTH Aachen; Aachen Germany
- Juelich-Aachen Research Alliance - Translational Brain Medicine (JARA Brain); Aachen Germany
| | - Gary Anthony Brook
- Institute of Neuropathology; University Hospital RWTH Aachen; Aachen Germany
- Juelich-Aachen Research Alliance - Translational Brain Medicine (JARA Brain); Aachen Germany
| | - Norbert Pallua
- Department of Plastic Surgery, Reconstructive and Hand Surgery; Burn Center; University Hospital RWTH Aachen; Pauwelsstrasse 30 52074 Aachen Germany
| | - Ahmet Bozkurt
- Department of Plastic Surgery, Reconstructive and Hand Surgery; Burn Center; University Hospital RWTH Aachen; Pauwelsstrasse 30 52074 Aachen Germany
- Department of Plastic & Aesthetic, Reconstructive & Hand Surgery; Center for Reconstructive Microsurgery and Peripheral Nerve Surgery (ZEMPEN) Markus Hospital; Frankfurt Germany
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Trindade AB, Schestatsky P, Torres VF, Gomes C, Gianotti GC, Paz AHDR, Terraciano PB, Marques JMV, Guimarães KM, Graça DL, Cirne-Lima EO, Contesini EA. Functional and regenerative effects of local administration of autologous mononuclear bone marrow cells combined with silicone conduit on transected femoral nerve of rabbits. Res Vet Sci 2015; 102:27-33. [DOI: 10.1016/j.rvsc.2015.07.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 06/03/2015] [Accepted: 07/09/2015] [Indexed: 02/01/2023]
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Ke X, Li Q, Xu L, Zhang Y, Li D, Ma J, Mao X. Netrin-1 overexpression in bone marrow mesenchymal stem cells promotes functional recovery in a rat model of peripheral nerve injury. J Biomed Res 2015; 29:380-389. [PMID: 26445571 PMCID: PMC4585432 DOI: 10.7555/jbr.29.20140076] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2014] [Revised: 10/01/2014] [Accepted: 04/08/2015] [Indexed: 11/08/2022] Open
Abstract
Transplantation of bone marrow mesenchymal stem cells (BMSCs) has been developed as a new method of treating diseases of the peripheral nervous system. While netrin-1 is a critical molecule for axonal path finding and nerve growth, it may also affect vascular network formation. Here, we investigated the effect of transplanting BMSCs that produce netrin-1 in a rat model of sciatic nerve crush injury. We introduced a sciatic nerve crush injury, and then injected 1×10(6) BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-1-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve conduction and detected mRNA expressions of netrin-1 receptors UNC5B and Deleted in Colorectal Cancer (DCC), and neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) by real-time PCR. We also detected protein expressions of BDNF and NGF by Western blotting assays and examined BMSCs that incorporated into myelin and vascellum. The results showed that BMSCs infected by Ad5-Netrin-1-EGFP significantly improved the function of the sciatic nerve, and led to increased expression of BDNF and NGF (P<0.05). Moreover, 28 days after injury, more Schwann cells were found in BMSCs infected by Ad5-Netrin-1-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury.
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Affiliation(s)
- Xianjin Ke
- Department of Neurology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China
| | - Qian Li
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China
| | - Li Xu
- Department of Neurology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China
| | - Ying Zhang
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China
| | - Dongmei Li
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China
| | - Jianhua Ma
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China
| | - Xiaoming Mao
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China
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Zhou LN, Zhang JW, Liu XL, Zhou LH. Co-Graft of Bone Marrow Stromal Cells and Schwann Cells Into Acellular Nerve Scaffold for Sciatic Nerve Regeneration in Rats. J Oral Maxillofac Surg 2015; 73:1651-60. [DOI: 10.1016/j.joms.2015.02.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Revised: 02/06/2015] [Accepted: 02/06/2015] [Indexed: 01/21/2023]
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Wang Y, Li ZW, Luo M, Li YJ, Zhang KQ. Biological conduits combining bone marrow mesenchymal stem cells and extracellular matrix to treat long-segment sciatic nerve defects. Neural Regen Res 2015. [PMID: 26199615 PMCID: PMC4498360 DOI: 10.4103/1673-5374.158362] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The transplantation of polylactic glycolic acid conduits combining bone marrow mesenchymal stem cells and extracellular matrix gel for the repair of sciatic nerve injury is effective in some respects, but few data comparing the biomechanical factors related to the sciatic nerve are available. In the present study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit models were repaired with autologous nerve, a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks, mechanical testing was performed to determine the stress relaxation and creep parameters. Following sciatic nerve injury, the magnitudes of the stress decrease and strain increase at 7,200 seconds were largest in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group, followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group, and then the autologous nerve group. Hematoxylin-eosin staining demonstrated that compared with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells group and the autologous nerve group, a more complete sciatic nerve regeneration was found, including good myelination, regularly arranged nerve fibers, and a completely degraded and resorbed conduit, in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group. These results indicate that bridging 10-mm sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel construct increases the stress relaxation under a constant strain, reducing anastomotic tension. Large elongations under a constant physiological load can limit the anastomotic opening and shift, which is beneficial for the regeneration and functional reconstruction of sciatic nerve. Better regeneration was found with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells + extracellular matrix gel grafts than with the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells grafts and the autologous nerve grafts.
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Affiliation(s)
- Yang Wang
- Department of Orthopedics, China-Japan Friendship Hospital, Jilin University, Changchun, Jilin Province, China
| | - Zheng-Wei Li
- Department of Orthopedics, Second Hospital, Jilin University, Changchun, Jilin Province, China
| | - Min Luo
- Department of Orthopedics, China-Japan Friendship Hospital, Jilin University, Changchun, Jilin Province, China
| | - Ya-Jun Li
- Mathematics School, Jilin University, Changchun, Jilin Province, China
| | - Ke-Qiang Zhang
- Department of Orthopedics, Second Hospital, Jilin University, Changchun, Jilin Province, China
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