内容简介
本研究论文聚焦锂负载电纺丝纳米纤维支架增强大鼠坐骨神经轴突再生和功能恢复。越来越多的证据表明,经过工程改造的神经移植在周围神经损伤(PNIs)再生方面具有巨大潜力。虽然大多数研究仅关注移植物的形貌特征,但我们在应用纳米支架时考虑了生物物理学和生物化学两个方面。为了实现这一点,我们制造了一种含有聚乳酸纳米纤维和锂离子(Li)的静电纺纳米支架(ENS),其中的锂离子是一种Wnt/β-连环蛋白信号激活剂。此外,我们将人类脂肪来源的间充质干细胞(hADMSCs)种植到这种工程支架上,以检查是否能诱导它们向施旺样细胞分化。我们还通过在PNI大鼠模型中进行移植来进一步检查支架在神经再生方面的功效。结果显示,含锂的ENS在11天内逐渐释放锂,其浓度在0.02至(3.64±0.10) mmol/L范围内,并上调了已分化的hADMSCs中的Wnt/β-连环蛋白靶基因(cyclinD1和c-Myc)以及施旺细胞标记物(重组生长相关蛋白43(GAP43)、单克隆抗体S100钙结合蛋白B(S100B)、胶质酸性纤维蛋白(GFAP)和SOX10)的表达。在PNI大鼠模型中,植入含锂的ENS(是否有细胞)改善了感觉和运动功能以及受伤神经的电生理特性等行为特征。通过对植入锂离子支架的坐骨神经进行组织学分析,进一步验证了这种改善的功能,结果显示没有纤维结缔组织,而是增强了有机化的髓鞘轴突。锂离子饱和的ENS在促进hADMSCs的施旺细胞分化和受伤坐骨神经轴突再生方面的潜力,表明其在周围神经组织工程中的应用潜力。
引用本文(点击最下方阅读原文可下载PDF)
Dolatyar B, Zeynali B, Shabani I, et al., 2004. Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds. Bio-des Manuf 7(5):701–720. https://doi.org/10.1007/s42242-024-00304-3
文章导读
图1 人脂肪源性间充质干细胞向施旺细胞样细胞的分化
图2 人脂肪来源间充质干细胞在电纺丝纳米纤维支架上的活力和增殖
图3 周围神经损伤大鼠模型感觉和运动功能恢复分析
参考文献
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1. Suzuki K, Tanaka H, Ebara M et al (2017) Electrospun nanofiber sheets incorporating methylcobalamin promote nerve regeneration and functional recovery in a rat sciatic nerve crush injury model. Acta Biomater 53:250–259. https://doi.org/10.1016/j.actbio.2017.02.004
2. Hussain G, Wang J, Rasul A et al (2020) Current status of therapeutic approaches against peripheral nerve injuries: a detailed story from injury to recovery. Int J Biol Sci 16(1):116–134. https://doi.org/10.7150/ijbs.35653
3. Soto PA, Vence M, Piñero GM et al (2021) Sciatic nerve regeneration after traumatic injury using magnetic targeted adipose-derived mesenchymal stem cells. Acta Biomater 130:234–247. https://doi.org/10.1016/j.actbio.2021.05.050
4. Nocera G, Jacob C (2020) Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury. Cell Mol Life Sci 77(20):3977–3989. https://doi.org/10.1007/s00018-020-03516-9
5. Chrząszcz P, Derbisz K, Suszyński K et al (2018) Application of peripheral nerve conduits in clinical practice: a literature review. Neurol Neurochir Pol 52(4):427–435. https://doi.org/10.1016/j.pjnns.2018.06.003
6. Bu YZ, Wang XH, Li LX et al (2020) Lithium loaded octa-poly(ethylene glycol) based adhesive facilitates axon regeneration and reconnection of transected peripheral nerves. Adv Healthc Mater 9(13):e2000268. https://doi.org/10.1002/adhm.202000268
7. Regas I, Loisel F, Haight H et al (2020) Functionalized nerve conduits for peripheral nerve regeneration: a literature review. Hand Surg Rehabil 39(5):343–351. https://doi.org/10.1016/j.hansur.2020.05.007
8. Ma Y, Gao HC, Wang H et al (2021) Engineering topography: effects on nerve cell behaviors and applications in peripheral nerve repair. J Mater Chem B 9(32):6310–6325. https://doi.org/10.1039/d1tb00782c
9. Liao DP, Li XJ, Dong Y et al (2017) The role of Wnt/β-catenin signaling pathway in the transdifferentiation from periodontal ligament stem cells to Schwann cells. Cell Reprogram 19(6):384–388. https://doi.org/10.1089/cell.2017.0017
10. Tawk M, Makoukji J, Belle M et al (2011) Wnt/β-catenin signaling is an essential and direct driver of myelin gene expression and myelinogenesis. J Neurosci 31(10):3729–3742. https://doi.org/10.1523/JNEUROSCI.4270-10.2011
11. Grigoryan T, Stein S, Qi JJ et al (2013) Wnt/Rspondin/β-catenin signals control axonal sorting and lineage progression in Schwann cell development. Proc Natl Acad Sci USA 110(45):18174–18179. https://doi.org/10.1073/pnas.1310490110
12. Phiel CJ, Klein PS (2001) Molecular targets of lithium action. Annu Rev Pharmacol Toxicol 41(1):789–813. https://doi.org/10.1146/annurev.pharmtox.41.1.789
13. Kuffler DP (2022) Can lithium enhance the extent of axon regeneration and neurological recovery following peripheral nerve trauma? Neural Regener Res 17(5):948–952. https://doi.org/10.4103/1673-5374.324830
14. Basselin M, Villacreses NE, Lee HJ et al (2007) Chronic lithium administration attenuates up-regulated brain arachidonic acid metabolism in a rat model of neuroinflammation. J Neurochem 102(3):761–772. https://doi.org/10.1111/j.1471-4159.2007.04593.x
15. Chuang DM (2005) The antiapoptotic actions of mood stabilizers: molecular mechanisms and therapeutic potentials. Ann NY Acad Sci 1053(1):195–204. https://doi.org/10.1196/annals.1344.018
16. Chiu CT, Chuang DM (2011) Neuroprotective action of lithium in disorders of the central nervous system. J Cent South Univ (Med Sci) 36(6):461–475. https://doi.org/10.3969/j.issn.1672-7347.2011.06.001
17. Yasuda S, Liang MH, Marinova Z et al (2009) The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons. Mol Psychiatr 14(1):51–59. https://doi.org/10.1038/sj.mp.4002099
18. Fu R, Tang Y, Ling ZM et al (2014) Lithium enhances survival and regrowth of spinal motoneurons after ventral root avulsion. BMC Neurosci 15(1):84. https://doi.org/10.1186/1471-2202-15-84
19. Noble W, Planel E, Zehr C et al (2005) Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci USA 102(19):6990–6995. https://doi.org/10.1073/pnas.0500466102
20. Arraf Z, Youdim MBH (2004) Prevention of MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) dopaminergic neurotoxicity in mice by chronic lithium: involvements of Bcl-2 and Bax. Neuropharmacology 46(8):1130–1140. https://doi.org/10.1016/j.neuropharm.2004.02.005
21. Wei H, Qin ZH, Senatorov VV et al (2001) Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington’s disease. Neuroscience 106(3):603–612. https://doi.org/10.1016/s0306-4522(01)00311-6
22. van Eijk RPA, Jones AR, Sproviero W et al (2017) Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials. Neurology 89(18):1915–1922. https://doi.org/10.1212/WNL.0000000000004606
23. de Sarno P, Axtell RC, Raman C et al (2008) Lithium prevents and ameliorates experimental autoimmune encephalomyelitis. J Immunol 181(1):338–345. https://doi.org/10.4049/jimmunol.181.1.338
24. Makoukji J, Belle M, Meffre D et al (2012) Lithium enhances remyelination of peripheral nerves. Proc Natl Acad Sci USA 109(10):3973–3978. https://doi.org/10.1073/pnas.1121367109
25. Chen YX, Weng J, Han DY et al (2016) GSK3β inhibition accelerates axon debris clearance and new axon remyelination. Am J Transl Res 8(12):5410–5420
26. Gu XK, Li XR, Lu ML et al (2020) Lithium promotes proliferation and suppresses migration of Schwann cells. Neural Regener Res 15(10):1955–1961. https://doi.org/10.4103/1673-5374.280324
27. Zhang LQ, Zhang WM, Deng LX et al (2018) Transplantation of a peripheral nerve with neural stem cells plus lithium chloride injection promote the recovery of rat spinal cord injury. Cell Transplant 27(3):471–484. https://doi.org/10.1177/0963689717752945
28. Ala M, Mohammad Jafari R, Nematian H et al (2021) Neuroprotective effect of intravitreal single-dose lithium chloride after optic nerve injury in rats. Curr Eye Res 46(4):558–567. https://doi.org/10.1080/02713683.2020.1808999
29. Lin YC, Oh SJ, Marra KG (2013) Synergistic lithium chloride and glial cell line-derived neurotrophic factor delivery for peripheral nerve repair in a rodent sciatic nerve injury model. Plast Reconstr Surg 132(2):251e–262e. https://doi.org/10.1097/PRS.0b013e31829588cf
30. Shabani I, Haddadi-Asl V, Soleimani M et al (2014) Ion-exchange polymer nanofibers for enhanced osteogenic differentiation of stem cells and ectopic bone formation. ACS Appl Mater Interfaces 6(1):72–82. https://doi.org/10.1021/am404500c
31. Razavi S, Mardani M, Kazemi M et al (2013) Effect of leukemia inhibitory factor on the myelinogenic ability of Schwann-like cells induced from human adipose-derived stem cells. Cell Mol Neurobiol 33(2):283–289. https://doi.org/10.1007/s10571-012-9895-2
32. Dolatyar B, Zeynali B, Shabani I et al (2023) High-efficient serum-free differentiation of trabecular meshwork mesenchymal stem cells into Schwann-like cells on polylactide electrospun nanofibrous scaffolds. Neurosci Lett 813:137417. https://doi.org/10.1016/j.neulet.2023.137417
33. Hedayati S, Parvaneh Tafreshi A, Moradi N et al (2018) Inhibition of transforming growth factor-β signaling pathway enhances the osteogenic differentiation of unrestricted somatic stem cells. J Cell Biochem 119(11):9327–9333. https://doi.org/10.1002/jcb.27209
34. Munir H, Ward LS, Sheriff L et al (2017) Adipogenic differentiation of mesenchymal stem cells alters their immunomodulatory properties in a tissue-specific manner. Stem Cells 35(6):1636–1646. https://doi.org/10.1002/stem.2622
35. Dzobo K, Turnley T, Wishart A et al (2016) Fibroblast-derived extracellular matrix induces chondrogenic differentiation in human adipose-derived mesenchymal stromal/stem cells in vitro. Int J Mol Sci 17(8):1259. https://doi.org/10.3390/ijms17081259
36. Sahebdel F, Parvaneh Tafreshi A, Arefian E et al (2022) Wnt/β-catenin signaling pathway is involved in early dopaminergic differentiation of trabecular meshwork-derived mesenchymal stem cells. J Cell Biochem 123(6):1120–1129. https://doi.org/10.1002/jcb.30269
37. Mohammadi Amirabad L, Massumi M, Shamsara M et al (2017) Enhanced cardiac differentiation of human cardiovascular disease patient specific induced pluripotent stem cells by applying unidirectional electrical pulses using aligned electroactive nanofibrous scaffolds. ACS Appl Mater Interfaces 9(8):6849–6864. https://doi.org/10.1021/acsami.6b15271
38. Kehtari M, Beiki B, Zeynali B et al (2019) Decellularized Wharton’s jelly extracellular matrix as a promising scaffold for promoting hepatic differentiation of human induced pluripotent stem cells. J Cell Biochem 120(4):6683–6697. https://doi.org/10.1002/jcb.27965
39. Navarro X (2016) Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: a critical overview. Eur J Neurosci 43(3):271–286. https://doi.org/10.1111/ejn.13033
40. Nishimoto S, Tanaka H, Okamoto M et al (2015) Methylcobalamin promotes the differentiation of Schwann cells and remyelination in lysophosphatidylcholine-induced demyelination of the rat sciatic nerve. Front Cell Neurosci 9:298. https://doi.org/10.3389/fncel.2015.00298
41. Bain JR, Mackinnon SE, Hunter DA (1989) Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg 83(1):129–136. https://doi.org/10.1097/00006534-198901000-00024
42. Sorrenti V, Cecchetto C, Maschietto M et al (2021) Understanding the effects of anesthesia on cortical electrophysiological recordings: a scoping review. Int J Mol Sci 22(3):1286. https://doi.org/10.3390/ijms22031286
43. Mirakhori F, Zeynali B, Tafreshi AP et al (2013) Lithium induces follicular atresia in rat ovary through a GSK-3β/β-catenin dependent mechanism. Mol Reprod Dev 80(4):286–296. https://doi.org/10.1002/mrd.22163
44. Imani F, Karimi-Soflou R, Shabani I et al (2021) PLA electrospun nanofibers modified with polypyrrole-grafted gelatin as bioactive electroconductive scaffold. Polymer 218:123487. https://doi.org/10.1016/j.polymer.2021.123487
45. Dautoo UK, Shandil Y, Ranote S et al (2022) New efficient poly(acrylic acid)-based bifunctional Cu2+ ions adsorbents. Colloids Surf A 635:128090. https://doi.org/10.1016/j.colsurfa.2021.128090
46. Kawai T, Ohtsuki C, Kamitakahara M et al (2004) Coating of an apatite layer on polyamide films containing sulfonic groups by a biomimetic process. Biomaterials 25(19):4529–4534. https://doi.org/10.1016/j.biomaterials.2003.11.039
47. Miyazaki T, Ohtsuki C, Akioka Y et al (2003) Apatite deposition on polyamide films containing carboxyl group in a biomimetic solution. J Mater Sci Mater Med 14(7):569–574. https://doi.org/10.1023/a:1024000821368
48. Sun WJ, Sun CK, Lin H et al (2009) The effect of collagen-binding NGF-β on the promotion of sciatic nerve regeneration in a rat sciatic nerve crush injury model. Biomaterials 30(27):4649–4656. https://doi.org/10.1016/j.biomaterials.2009.05.037
49. Renno WM, Al-Maghrebi M, Alshammari A et al (2013) (−)-Epigallocatechin-3-gallate (EGCG) attenuates peripheral nerve degeneration in rat sciatic nerve crush injury. Neurochem Int 62(3):221–231. https://doi.org/10.1016/j.neuint.2012.12.018
50. Kocman AE, Dag I, Sengel T et al (2020) The effect of lithium and lithium-loaded hyaluronic acid hydrogel applications on nerve regeneration and recovery of motor functions in peripheral nerve injury. Rend Fis Acc Lincei 31(3):889–904. https://doi.org/10.1007/s12210-020-00919-5
51. Jahromi HK, Farzin A, Hasanzadeh E et al (2020) Enhanced sciatic nerve regeneration by poly-l-lactic acid/multi-wall carbon nanotube neural guidance conduit containing Schwann cells and curcumin encapsulated chitosan nanoparticles in rat. Mater Sci Eng C Mater Biol Appl 109:110564. https://doi.org/10.1016/j.msec.2019.110564
52. Jessen KR, Mirsky R (2016) The repair Schwann cell and its function in regenerating nerves. J Physiol 594(13):3521–3531. https://doi.org/10.1113/JP270874
53. Chew LJ, Shen WP, Ming XT et al (2011) SRY-box containing gene 17 regulates the Wnt/β-catenin signaling pathway in oligodendrocyte progenitor cells. J Neurosci 31(39):13921–13935. https://doi.org/10.1523/JNEUROSCI.3343-11.2011
54. Meffre D, Massaad C, Grenier J (2015) Lithium chloride stimulates PLP and MBP expression in oligodendrocytes via Wnt/β-catenin and Akt/CREB pathways. Neuroscience 284:962–971. https://doi.org/10.1016/j.neuroscience.2014.10.064
55. Hichor M, Sampathkumar NK, Montanaro J et al (2017) Paraquat induces peripheral myelin disruption and locomotor defects: crosstalk with LXR and Wnt pathways. Antioxidant Redox Signal 27(3):168–183. https://doi.org/10.1089/ars.2016.6711
56. Makoukji J, Meffre D, Grenier J et al (2011) Interplay between LXR and Wnt/β-catenin signaling in the negative regulation of peripheral myelin genes by oxysterols. J Neurosci 31(26):9620–9629. https://doi.org/10.1523/JNEUROSCI.0761-11.2011
57. Fancy SPJ, Baranzini SE, Zhao C et al (2009) Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev 23(13):1571–1585. https://doi.org/10.1101/gad.1806309
58. Yang L, Yang F, Liu JR et al (2018) Protective effect of lithium on Schwann cell transplantation via Wnt/beta-catenin signaling pathway after spinal cord injury in vitro and vivo. Int J Clin Exp Med 11(10):10487–10495
59. Sun X, Zhu Y, Yin HY et al (2018) Differentiation of adipose-derived stem cells into Schwann cell-like cells through intermittent induction: potential advantage of cellular transient memory function. Stem Cell Res Ther 9(1):133. https://doi.org/10.1186/s13287-018-0884-3
60. Rao ZL, Lin ZD, Song PP et al (2022) Biomaterial-based Schwann cell transplantation and Schwann cell-derived biomaterials for nerve regeneration. Front Cell Neurosci 16:926222. https://doi.org/10.3389/fncel.2022.926222
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