Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2018 Jun 23

PMID 29931510

Citations 119

Authors

Vesna Bucan

Desiree Vaslaitis

Claas-Tido Peck

Sarah Strauss

Peter M Vogt

Christine Radtke

Affiliations

Soon will be listed here.

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.

Citing Articles

Conditioning period impacts the morphology and proliferative effect of extracellular vesicles derived from rat adipose tissue derived stromal cell.

Anton B, Maximilian H, Flavia M, Lorenz S, Paul S, Sarah S J Nanobiotechnology. 2025; 23(1):164.

PMID: 40033315 PMC: 11877948. DOI: 10.1186/s12951-025-03273-6.

Human endometrial stem cell-derived small extracellular vesicles enhance neurite outgrowth and peripheral nerve regeneration through activating the PI3K/AKT signaling pathway.

Namini M, Beheshtizadeh N, Ebrahimi-Barough S, Ai J J Transl Med. 2025; 23(1):6.

PMID: 39754260 PMC: 11699817. DOI: 10.1186/s12967-024-06048-z.

Amelioration of full-thickness cutaneous wound healing using stem cell exosome and zinc oxide nanoparticles in rats.

Salem M, Ateya A, Shouman Z, Salama B, Hamed B, Batiha G Heliyon. 2024; 10(21):e38994.

PMID: 39568845 PMC: 11577189. DOI: 10.1016/j.heliyon.2024.e38994.

Research hotspots and trends of mesenchymal stem cell-derived extracellular vesicles for drug delivery: a bibliometric and visualization analysis from 2013 to 2023.

Zhao T, Mu Y, Deng H, Liang K, Zhou F, Lin Q Front Cell Dev Biol. 2024; 12:1412363.

PMID: 39539963 PMC: 11557358. DOI: 10.3389/fcell.2024.1412363.

Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury: state of the art and future perspectives.

Aldali F, Deng C, Nie M, Chen H Neural Regen Res. 2024; 20(11):3151-3171.

PMID: 39435603 PMC: 11881730. DOI: 10.4103/NRR.NRR-D-24-00235.

References

Terenghi G . Peripheral nerve regeneration and neurotrophic factors. J Anat. 1999; 194 ( Pt 1):1-14. PMC: 1467889. DOI: 10.1046/j.1469-7580.1999.19410001.x. View

EVANS G, Brandt K, Widmer M, Lu L, Meszlenyi R, Gupta P . In vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration. Biomaterials. 1999; 20(12):1109-15. DOI: 10.1016/s0142-9612(99)00010-1. View

Scholzen T, Gerdes J . The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000; 182(3):311-22. DOI: 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9. View

Haas S, Bauer P, Rolfs A, Wree A . Immunocytochemical characterization of in vitro PKH26-labelled and intracerebrally transplanted neonatal cells. Acta Histochem. 2000; 102(3):273-80. DOI: 10.1078/S0065-1281(04)70035-5. View

EVANS G, Brandt K, Niederbichler A, Chauvin P, Herrman S, Bogle M . Clinical long-term in vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration. J Biomater Sci Polym Ed. 2001; 11(8):869-78. DOI: 10.1163/156856200744066. View

Varejao A, Meek M, Ferreira A, Patricio J, Cabrita A . Functional evaluation of peripheral nerve regeneration in the rat: walking track analysis. J Neurosci Methods. 2001; 108(1):1-9. DOI: 10.1016/s0165-0270(01)00378-8. View

Mosahebi A, Fuller P, Wiberg M, Terenghi G . Effect of allogeneic Schwann cell transplantation on peripheral nerve regeneration. Exp Neurol. 2002; 173(2):213-23. DOI: 10.1006/exnr.2001.7846. View

Ngo T, Waggoner P, Romero A, Nelson K, Eberhart R, Smith G . Poly(L-Lactide) microfilaments enhance peripheral nerve regeneration across extended nerve lesions. J Neurosci Res. 2003; 72(2):227-38. DOI: 10.1002/jnr.10570. View

Cuevas P, Carceller F, Garcia-Gomez I, Yan M, Dujovny M . Bone marrow stromal cell implantation for peripheral nerve repair. Neurol Res. 2004; 26(2):230-2. DOI: 10.1179/016164104225013897. View

10.

Mimura T, Dezawa M, Kanno H, Sawada H, Yamamoto I . Peripheral nerve regeneration by transplantation of bone marrow stromal cell-derived Schwann cells in adult rats. J Neurosurg. 2004; 101(5):806-12. DOI: 10.3171/jns.2004.101.5.0806. View

11.

Rutkowski G, Miller C, Jeftinija S, Mallapragada S . Synergistic effects of micropatterned biodegradable conduits and Schwann cells on sciatic nerve regeneration. J Neural Eng. 2005; 1(3):151-7. DOI: 10.1088/1741-2560/1/3/004. View

12.

Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P . Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia. 2006; 20(5):847-56. DOI: 10.1038/sj.leu.2404132. View

13.

Lopes F, de Moura Campos L, Correa Jr J, Balduino A, Lora S, Langone F . Bone marrow stromal cells and resorbable collagen guidance tubes enhance sciatic nerve regeneration in mice. Exp Neurol. 2006; 198(2):457-68. DOI: 10.1016/j.expneurol.2005.12.019. View

14.

Li Q, Ping P, Jiang H, Liu K . Nerve conduit filled with GDNF gene-modified Schwann cells enhances regeneration of the peripheral nerve. Microsurgery. 2006; 26(2):116-21. DOI: 10.1002/micr.20192. View

15.

Caplan A, Dennis J . Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006; 98(5):1076-84. DOI: 10.1002/jcb.20886. View

16.

Chalfoun C, Wirth G, Evans G . Tissue engineered nerve constructs: where do we stand?. J Cell Mol Med. 2006; 10(2):309-17. PMC: 3933123. DOI: 10.1111/j.1582-4934.2006.tb00401.x. View

17.

Marchesi C, Pluderi M, Colleoni F, Belicchi M, Meregalli M, Farini A . Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection. Glia. 2007; 55(4):425-38. DOI: 10.1002/glia.20470. View

18.

Chen C, Ou Y, Liao S, Chen W, Chen S, Wu C . Transplantation of bone marrow stromal cells for peripheral nerve repair. Exp Neurol. 2007; 204(1):443-53. DOI: 10.1016/j.expneurol.2006.12.004. View

19.

Hu J, Zhu Q, Liu X, Xu Y, Zhu J . Repair of extended peripheral nerve lesions in rhesus monkeys using acellular allogenic nerve grafts implanted with autologous mesenchymal stem cells. Exp Neurol. 2007; 204(2):658-66. DOI: 10.1016/j.expneurol.2006.11.018. View

20.

Park H, Temenoff J, Tabata Y, Caplan A, Mikos A . Injectable biodegradable hydrogel composites for rabbit marrow mesenchymal stem cell and growth factor delivery for cartilage tissue engineering. Biomaterials. 2007; 28(21):3217-27. PMC: 2964378. DOI: 10.1016/j.biomaterials.2007.03.030. View