Adipose-derived mesenchymal stem cells enhance regeneration in a chronic peripheral sciatic nerve injury Sprague-Dawley rat model
DOI:
https://doi.org/10.13181/mji.oa.257780Keywords:
animal model, mesenchymal stem cells, sciatic neuropathyAbstract
BACKGROUND Obtaining optimal functional outcomes in patients with chronic peripheral nerve injuries (PNIs) remains challenging due to the limited regeneration of the neuromuscular junction (NMJ). Adipose-derived mesenchymal stem cells (AD-MSCs) can differentiate into Schwann-like cells, secrete neurotrophic factors, and recruit native Schwann cells. This study aimed to analyze the effects of AD-MSCs on functional outcomes in a chronic PNI model.
METHODS An in vivo study was performed using 20 male Sprague-Dawley rats with chronic PNI of the right sciatic nerve. Rats were divided into two groups: the AD-MSC group (n = 10), receiving human AD-MSC injections in the NMJ; and the control group (n = 10), receiving normal saline injections. Walking track analysis and electrophysiological assessments were performed 8 weeks after the nerve repair. Postmortem gastrocnemius muscle weights and immunohistochemical examinations were also performed.
RESULTS The AD-MSCs showed significantly larger fiber diameters than the control group (45.54 [13.1] versus 35.46 [6.64]; p = 0.011). While clinical, electrophysiological, and gastrocnemius muscle weight data suggested a trend toward improved outcomes in the AD-MSCs group, the differences were not statistically significant.
CONCLUSIONS AD-MSC implantation may enhance nerve regeneration, as demonstrated by a better outcome profile in the AD-MSCs group.
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References
2. Wojtkiewicz DM, Saunders J, Domeshek L, Novak CB, Kaskutas V, Mackinnon SE. Social impact of peripheral nerve injuries. Hand (N Y). 2015 Jun;10(2):161–7.
3. Tan RES, Jeyaratnam S, Lim AYT. Updates in Peripheral Nerve Surgery of the Upper Extremity: Diagnosis and Treatment Options. Ann Transl Med. 2023;11(11):391.
4. Slavin BR, Sarhane KA, von Guionneau N, Hanwright PJ, Qiu C, Mao HQ, et al. Insulin-Like Growth Factor-1: A Promising Therapeutic Target for Peripheral Nerve Injury. Front Bioeng Biotechnol. 2021;9:695850.
5. Menorca RMG, Fussell TS, Elfar JC. Nerve physiology: mechanisms of injury and recovery. Hand Clin. 2013 Aug;29(3):317–30.
6. Vannucci B, Santosa KB, Keane AM, Jablonka-Shariff A, Lu CY, Yan Y, et al. What is Normal? Neuromuscular junction reinnervation after nerve injury. Muscle Nerve. 2019;60(5):604–12.
7. Huang X, Jiang J, Xu J. Denervation-Related Neuromuscular Junction Changes: From Degeneration to Regeneration. Front Mol Neurosci. 2022;14(February):1–8.
8. Sugimura-Wakayama Y, Katagiri W, Osugi M, Kawai T, Ogata K, Sakaguchi K, et al. Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth. Stem Cells Dev. 2015 Nov;24(22):2687–99.
9. Chen O, Wu M, Jiang L. The Effect of Hypoxic Preconditioning on Induced Schwann Cells under Hypoxic Conditions. PLoS One. 2015;10(10):1–16.
10. Li LK, Huang WC, Hsueh YY, Yamauchi K, Olivares N, Davila R, et al. Intramuscular delivery of neural crest stem cell spheroids enhances neuromuscular regeneration after denervation injury. Stem Cell Res Ther. 2022;1–14.
11. Fu X, Tong Z, Li QI, Niu Q, Zhang ZHE. Induction of adipose-derived stem cells into Schwann-like cells and observation of Schwann-like cell proliferation. Mol Med Rep. 2016;14:1187–93.
12. Georgiou M, Golding JP, Loughlin AJ, Kingham PJ, Phillips JB. Engineered neural tissue with aligned, differentiated adipose-derived stem cells promotes peripheral nerve regeneration across a critical sized defect in rat sciatic nerve. Biomaterials. 2015;37:242–51.
13. Tomita K, Madura T, Sakai Y, Yano K, Terenghi G, Hosokawa K. Glial differentiation of human adipose-derived stem cells: Implications for cell-based transplantation therapy. Neuroscience. 2013;236:55–65.
14. Kolar MK, Kingham PJ. Regenerative effects of adipose-tissue-derived stem cells for treatment of peripheral nerve injuries. Biochem Soc Trans doi. 2014;42(3):697–701.
15. Pawitan J, Liem I, Suryani D, Bustami A, Yuridian R. Simple lipoaspirate washing using a coffee filter. Asian Biomed. 2013 Jun;7:333–8.
16. Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg. 1989 Jan;83(1):129–38.
17. Olney RK. Guidelines in electrodiagnostic medicine. Consensus criteria for the diagnosis of partial conduction block. Muscle Nerve Suppl. 1999;8:S225-9.
18. Jiang L, Jones S, Jia X. Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities. Int J Mol Sci. 2017 Jan;18(1).
19. Heine W, Conant K, Griffin JW, Höke A. Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves. Exp Neurol. 2004 Oct;189(2):231–40.
20. Jones RA, Reich CD, Dissanayake KN, Simmen MW, Gillingwater TH. NMJ-morph reveals principal components of synaptic morphology influencing structure – function relationships at the neuromuscular junction. 2019;
21. Jones RA, Reich CD, Dissanayake KN, Kristmundsdottir F, Findlater GS, Ribchester RR, et al. NMJ-morph reveals principal components of synaptic morphology influencing structure-function relationships at the neuromuscular junction. Open Biol. 2016;6(12).
22. Zhang RC, Du WQ, Zhang JY, Yu SX, Lu FZ, Ding HM, et al. Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review. Neural Regen Res. 2021;16(11).
23. Mohammadi R, Vahabzadeh B, Amini K. Sciatic nerve regeneration induced by transplantation of in vitro bone marrow stromal cells into an inside-out artery graft in rat. J Cranio-Maxillofacial Surg. 2014;42(7):1389–96.
24. Sulaiman W, Gordon T. Neurobiology of peripheral nerve injury, regeneration, and functional recovery: from bench top research to bedside application. Ochsner J. 2013;13(1):100–8.
25. Sumarwoto T, Suroto H, Mahyudin F, Utomo DN, Romaniyanto, Tinduh D, et al. Role of adipose mesenchymal stem cells and secretome in peripheral nerve regeneration. Ann Med Surg. 2021;67(April):102482.
26. Kappos EA, Engels PE, Thommen S, Sprenger L. Epineural adipose derived stem cell injection in a sciatic rodent. Brain Behav. 2018;8(e01027):1–9.
27. Pikuła M, Marek-trzonkowska N, Wardowska A, Trzonkowski P. Adipose tissue-derived stem cells in clinical applications Adipose tissue-derived stem cells in clinical applications. Expert Opin Biol Ther. 2013;2598(13:10):1357–70.
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