Dose-response analysis after administration of a human platelet-derived exosome product on neurite outgrowth in vitro.

exosomes peripheral nerve injury peripheral nerve regeneration purified exosome product regenerative medicine

Journal

Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021

Informations de publication

Date de publication:
Nov 2023
Historique:
revised: 19 07 2023
received: 17 05 2023
accepted: 23 07 2023
pubmed: 4 8 2023
medline: 4 8 2023
entrez: 4 8 2023
Statut: ppublish

Résumé

Modulating the nerve's local microenvironment using exosomes is proposed to enhance nerve regeneration. This study aimed to determine the optimal dose of purified exosome product (PEP) required to exert maximal neurite extension. An in vitro dorsal root ganglion (DRG) neurite outgrowth assay was used to evaluate the effect of treatment with (i) 5% PEP, (ii) 10% PEP, (iii) 15% PEP, or (iv) 20% PEP on neurite extension (N = 9/group), compared to untreated controls. After 72 h, neurite extension was measured to quantify nerve regeneration. Live cell imaging was used to visualize neurite outgrowth during incubation. Treatment with 5% PEP resulted in the longest neurite extension and was superior to the untreated DRG (p = 0.003). Treatment with 10% PEP, 15% PEP, and 20% PEP was found to be comparable to controls (p = 0.12, p = 0.06, and p = 0.41, respectively) and each other. Live cell imaging suggested that PEP migrated towards the DRG neural regeneration site, compared to the persistent homogenous distribution of PEP in culture media alone. 5% PEP was found to be the optimal concentration for nerve regeneration based on this in vitro dose-response analysis.

Identifiants

pubmed: 37539665
doi: 10.1002/bit.28520
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3191-3199

Subventions

Organisme : Obaid Vascularized Composite Tissue Award (Mayo Clinic, MN, USA)

Informations de copyright

© 2023 Wiley Periodicals LLC.

Références

Acuto, O., Bartolo, V. D., & Michel, F. (2008). Tailoring T-cell receptor signals by proximal negative feedback mechanisms. Nature Reviews Immunology, 8(9), 699-712.
Alvites, R., Rita Caseiro, A., Santos Pedrosa, S., Vieira Branquinho, M., Ronchi, G., Geuna, S., Varejão, A. S. P., & Colette Maurício, A. (2018). Peripheral nerve injury and axonotmesis: State of the art and recent advances. Cogent Medicine, 5(1), 1466404.
Blanc, L., & Vidal, M. (2018). New insights into the function of Rab GTPases in the context of exosomal secretion. Small GTPases, 9(1-2), 95-106.
Bucan, V., Vaslaitis, D., Peck, C. T., Strauß, S., Vogt, P. M., & Radtke, C. (2019). Effect of exosomes from rat adipose-derived mesenchymal stem cells on neurite outgrowth and sciatic nerve regeneration after crush injury. Molecular Neurobiology, 56(3), 1812-1824. https://doi.org/10.1007/s12035-018-1172-z
Ciaramitaro, P., Mondelli, M., Logullo, F., Grimaldi, S., Battiston, B., Sard, A., Scarinzi, C., Migliaretti, G., Faccani, G., & Cocito, D. (2010). Traumatic peripheral nerve injuries: Epidemiological findings, neuropathic pain and quality of life in 158 patients. Journal of the Peripheral Nervous System, 15(2), 120-127.
Clements, M. P., Byrne, E., Camarillo Guerrero, L. F., Cattin, A.-L., Zakka, L., Ashraf, A., Burden, J. J., Khadayate, S., Lloyd, A. C., Marguerat, S., & Parrinello, S. (2017). The wound microenvironment reprograms Schwann cells to invasive mesenchymal-like cells to drive peripheral nerve regeneration. Neuron, 96(1), 98-114.e7. e117.
Corrado, C., Raimondo, S., Chiesi, A., Ciccia, F., De Leo, G., & Alessandro, R. (2013). Exosomes as intercellular signaling organelles involved in health and disease: Basic science and clinical applications. International Journal of Molecular Sciences, 14(3), 5338-5366.
Dimmitt, S. B., & Stampfer, H. G. (2009). Low drug doses may improve outcomes in chronic disease. Medical Journal of Australia, 191(9), 511-513.
Dong, R., Liu, Y., Yang, Y., Wang, H., Xu, Y., & Zhang, Z. (2019). MSC-derived exosomes-based therapy for peripheral nerve injury: A novel therapeutic strategy. BioMed Research International, 2019, 6458237.
Ekström, K., Omar, O., Granéli, C., Wang, X., Vazirisani, F., & Thomsen, P. (2013). Monocyte exosomes stimulate the osteogenic gene expression of mesenchymal stem cells. PLoS One, 8(9), e75227.
Gaudet, A. D., Popovich, P. G., & Ramer, M. S. (2011). Wallerian degeneration: Gaining perspective on inflammatory events after peripheral nerve injury. Journal of Neuroinflammation, 8(1), 110.
Herbert, C. B., Bittner, G. D., & Hubbell, J. A. (1996). Effects of fibrinolysis on neurite growth from dorsal root ganglia cultured in two- and three-dimensional fibrin gels. The Journal of Comparative Neurology, 365(3), 380-391. https://doi.org/10.1002/(sici)1096-9861(19960212)365:3<380::Aid-cne4>3.0.Co;2-0
Hudson, T. W., Liu, S. Y., & Schmidt, C. E. (2004). Engineering an improved acellular nerve graft via optimized chemical processing. Tissue Engineering, 10(9-10), 1346-1358.
Hudson, T. W., Zawko, S., Deister, C., Lundy, S., Hu, C. Y., Lee, K., & Schmidt, C. E. (2004). Optimized acellular nerve graft is immunologically tolerated and supports regeneration. Tissue Engineering, 10(11-12), 1641-1651.
Hundepool, C. A., Nijhuis, T. H. J., Mohseny, B., Selles, R. W., & Hovius, S. E. R. (2014). The effect of stem cells in bridging peripheral nerve defects: A meta-analysis: A review. Journal of Neurosurgery, 121(1), 195-209.
Ikumi, A., Gingery, A., Toyoshima, Y., Zhao, C., Moran, S. L., Livia, C., Rolland, T., Peterson, T., Sabbah, M. S., Boroumand, S., Saffari, T. M., Behfar, A., Shin, A. Y., & Amadio, P. C. (2021). Administration of purified exosome product in a rat sciatic serve reverse autograft model. Plastic & Reconstructive Surgery, 148(2), 200e-211e.
Jessen, K. R., & Mirsky, R. (2016). The repair Schwann cell and its function in regenerating nerves. The Journal of Physiology, 594(13), 3521-3531.
Kariminekoo, S., Movassaghpour, A., Rahimzadeh, A., Talebi, M., Shamsasenjan, K., & Akbarzadeh, A. (2016). Implications of mesenchymal stem cells in regenerative medicine. Artificial Cells, Nanomedicine, and Biotechnology, 44(3), 749-757.
Kholodenko, B. N., Rauch, N., Kolch, W., & Rukhlenko, O. S. (2021). A systematic analysis of signaling reactivation and drug resistance. Cell Reports, 35(8), 109157.
Kisby, C. K., Shadrin, I. Y., Rolland, T. J., Stalboerger, P. G., Zhou, B., Trabuco, E. C., Behfar, A., & Occhino, J. A. (2021). Exosome-induced vaginal tissue regeneration in a porcine mesh exposure model. Female Pelvic Medicine & Reconstructive Surgery, 27(10), 609-615. https://doi.org/10.1097/spv.0000000000001005
Li, P., Kaslan, M., Lee, S. H., Yao, J., & Gao, Z. (2017). Progress in exosome isolation techniques. Theranostics, 7(3), 789-804.
Liu, C. Y., Yin, G., Sun, Y. D., Lin, Y. F., Xie, Z., English, A. W., Li, Q. F., & Lin, H. D. (2020). Effect of exosomes from adipose-derived stem cells on the apoptosis of Schwann cells in peripheral nerve injury. CNS Neuroscience & Therapeutics, 26(2), 189-196.
Lundborg, G. (2000). A 25-year perspective of peripheral nerve surgery: Evolving neuroscientific concepts and clinical significance. The Journal of Hand Surgery, 25(3), 391-414.
Mathot, F., Rbia, N., Thaler, R., Bishop, A. T., Van Wijnen, A. J., & Shin, A. Y. (2020). Gene expression profiles of differentiated and undifferentiated adipose derived mesenchymal stem cells dynamically seeded onto a processed nerve allograft. Gene, 724, 144151.
Qi, J., Liu, Q., Reisdorf, R. L., Boroumand, S., Behfar, A., Moran, S. L., Amadio, P. C., Gingery, A., & Zhao, C. (2020). Characterization of a purified exosome product and its effects on canine flexor tenocyte biology. Journal of Orthopaedic Research, 38(8), 1845-1855.
Qing, L., Chen, H., Tang, J., & Jia, X. (2018). Exosomes and their microRNA cargo: New players in peripheral nerve regeneration. Neurorehabilitation and Neural Repair, 32(9), 765-776.
Rbia, N., & Shin, A. Y. (2017). The role of nerve graft substitutes in motor and mixed motor/sensory peripheral nerve injuries. The Journal of Hand Surgery, 42(5), 367-377.
Ren, Y., Zhang, S., Wang, Y., Jacobson, D. S., Reisdorf, R. L., Kuroiwa, T., Behfar, A., Moran, S. L., Steinmann, S. P., & Zhao, C. (2021). Effects of purified exosome product on rotator cuff tendon-bone healing in vitro and in vivo. Biomaterials, 276, 121019.
Rezaie, J., Ajezi, S., Avci, Ç. B., Karimipour, M., Geranmayeh, M. H., Nourazarian, A., Sokullu, E., Rezabakhsh, A., & Rahbarghazi, R. (2018). Exosomes and their application in biomedical field: Difficulties and advantages. Molecular Neurobiology, 55, 3372-3393.
Rinker, B., & Vyas, K. S. (2014). Clinical applications of autografts, conduits, and allografts in repair of nerve defects in the hand. Clinics in Plastic Surgery, 41(3), 533-550.
Rolland, T. J., Peterson, T. E., Singh, R. D., Rizzo, S. A., Boroumand, S., Shi, A., Witt, T. A., Nagel, M., Kisby, C. K., Park, S., Rowe, L. A., Paradise, C. R., Becher, L. R. E., Paradise, B. D., Stalboerger, P. G., Trabuco, E. C., & Behfar, A. (2022). Author correction: Exosome biopotentiated hydrogel restores damaged skeletal muscle in a porcine model of stress urinary incontinence. NPJ Regenerative Medicine, 7(1), 65.
Saffari, S., Saffari, T. M., Chan, K., Borschel, G. H., & Shin, A. Y. (2021). Mesenchymal stem cells and local tacrolimus delivery synergistically enhance neurite extension. Biotechnology and Bioengineering, 118(11), 4477-4487.
Saffari, S., Saffari, T. M., Ulrich, D. J., Hovius, S. E., & Shin, A. Y. (2021). The interaction of stem cells and vascularity in peripheral nerve regeneration. Neural Regeneration Research, 16(8), 1510-1517.
Samadian, H., Maleki, H., Fathollahi, A., Salehi, M., Gholizadeh, S., Derakhshankhah, H., Allahyari, Z., & Jaymand, M. (2020). Naturally occurring biological macromolecules-based hydrogels: Potential biomaterials for peripheral nerve regeneration. International Journal of Biological Macromolecules, 154, 795-817.
Shi, A., Li, J., Qiu, X., Sabbah, M., Boroumand, S., Huang, T. C. T., Zhao, C., Terzic, A., Behfar, A., & Moran, S. L. (2021). TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo. Theranostics, 11(13), 6616-6631. https://doi.org/10.7150/thno.57701
Shi, G., Long, Z., De la Vega, R. E., Behfar, A., Moran, S. L., Evans, C., & Zhao, C. (2023). Purified exosome product enhances chondrocyte survival and regeneration by modulating inflammation and promoting chondrogenesis. Regenerative Medicine, 18(1), 55-71.
Sowa, Y., Kishida, T., Imura, T., Numajiri, T., Nishino, K., Tabata, Y., & Mazda, O. (2016). Adipose-derived stem cells promote peripheral nerve regeneration in vivo without differentiation into Schwann-like lineage. Plastic and Reconstructive Surgery, 137(2), 318e-330e.
Stoll, G., & Müller, H. W. (1999). Nerve injury, axonal degeneration and neural regeneration: Basic insights. Brain Pathology, 9(2), 313-325.
Stolyarova, A., O'Dell, S. J., Marshall, J. F., & Izquierdo, A. (2014). Positive and negative feedback learning and associated dopamine and serotonin transporter binding after methamphetamine. Behavioural Brain Research, 271, 195-202.
Tajdaran, K., Chan, K., Shoichet, M. S., Gordon, T., & Borschel, G. H. (2019). Local delivery of FK506 to injured peripheral nerve enhances axon regeneration after surgical nerve repair in rats. Acta Biomaterialia, 96, 211-221.
Tajdaran, K., Chan, K., Zhang, J., Gordon, T., & Borschel, G. H. (2019). Local FK506 dose-dependent study using a novel three-dimensional organotypic assay. Biotechnology and Bioengineering, 116(2), 405-414.
Tajdaran, K., Shoichet, M. S., Gordon, T., & Borschel, G. H. (2015). A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506): Localized and sustained release of tacrolimus. Biotechnology and Bioengineering, 112(9), 1948-1953.
Terzis, J., Faibisoff, B., & Williams, H. B. (1975). The nerve gap: Suture under tension vs. graft. Plastic and Reconstructive Surgery, 56(2), 166-170.
Vitha, A. E., Kollefrath, A. W., Huang, C.-Y. C., & Garcia-Godoy, F. (2019). Characterization and therapeutic uses of exosomes: A new potential tool in orthopedics. Stem Cells and Development, 28(2), 141-150.
Wang, Y., Shi, G., Huang, T. C. T., Li, J., Long, Z., Reisdorf, R., Shin, A. Y., Amadio, P., Behfar, A., Zhao, C., & Moran, S. L. (2023). Enhancing functional recovery after segmental nerve defect using nerve allograft treated with plasma-derived exosome. Plastic & Reconstructive Surgery, 10-1097. https://doi.org/10.1097/prs.0000000000010389
Wellings, E. P., Huang, T. C. T., Li, J., Peterson, T. E., Hooke, A. W., Rosenbaum, A., Zhao, C. D., Behfar, A., Moran, S. L., & Houdek, M. T. (2021). Intrinsic tendon regeneration after application of purified exosome product: an in vivo study. Orthopaedic Journal of Sports Medicine, 9(12):232596712110629. https://doi.org/10.1177/23259671211062929
Wood, M. D., Kemp, S. W. P., Weber, C., Borschel, G. H., & Gordon, T. (2011). Outcome measures of peripheral nerve regeneration. Annals of Anatomy-Anatomischer Anzeiger, 193(4), 321-333.
Yuan, A., Rao, M. V., Veeranna, R. A., & Nixon, R. A. (2012). Neurofilaments at a glance. Journal of Cell Science, 125(14), 3257-3263.

Auteurs

Sara Saffari (S)

Department of Orthopedic Surgery, Division of Hand and Microvascular Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Department of Plastic Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.

Daan J Rademakers (DJ)

Department of Orthopedic Surgery, Division of Hand and Microvascular Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Department of Plastic Surgery, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.

Nicholas Pulos (N)

Department of Orthopedic Surgery, Division of Hand and Microvascular Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Alexander Y Shin (AY)

Department of Orthopedic Surgery, Division of Hand and Microvascular Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Classifications MeSH