AccScience Publishing / IJB / Volume 10 / Issue 1 / DOI: 10.36922/ijb.1045
Submit to IJB
Cite this article
261
Download
3118
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
RESEARCH ARTICLE

Near-infrared controlled release of mesenchymal stem cells secretome from bioprinted graphene-based microbeads for nerve regeneration

Giordano Perini1,2 ,  Valentina Palmieri2,3 ,  Marcello D’Ascenzo1,2 ,  Claudia Colussi2,4 ,  Claudio Grassi1,2 ,  Ginevra Friggeri2 ,  Alberto Augello2 ,  Lishan Cui1 ,  Massimiliano Papi1,2* ,  Marco De Spirito1,2
Show Less
1 Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy
2 Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy
3 Istituto dei Sistemi Complessi, CNR, Via dei Taurini 19, 00185 Rome, Italy
4 Istituto di analisi dei sistemi ed informatica “Antonio Ruberti,” CNR, Via dei Taurini 19, 00185 Rome, Italy
IJB 2024, 10(1), 1045 https://doi.org/10.36922/ijb.1045
Submitted: 5 June 2023 | Accepted: 10 July 2023 | Published: 4 August 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Nerve damage is a prevalent and debilitating condition with limited treatment options. Recent years have seen an increased incidence of neural damage due to factors such as aging populations and traumatic brain injuries. Addressing the urgent need for effective therapies, this study explores the controlled delivery of mesenchymal stem cells (MSCs) secretome, a complex mixture of bioactive factors, which is currently being investigated for its potential in nerve regeneration. The secretome offers significant advantages over stem cells themselves, as it can be more easily characterized and controlled, enabling precise regulation of therapeutic interventions. However, the challenge lies in delivering the secretome specifically to the target anatomical region. To overcome this limitation, we propose a novel approach utilizing near-infrared (NIR) radiation-responsive bioprinted alginate-graphene oxide (AGO) microbeads. Graphene oxide (GO) is a highly biocompatible material with unique properties, including NIR responsiveness, enabling controlled release of therapeutic agents upon NIR exposure. We hypothesized that AGO microbeads could encapsulate MSCs secretome and release it in a controlled manner using NIR radiation. To investigate our hypothesis, controlled damage was induced to hippocampal neurons, and MSCs secretome was encapsulated within AGO microbeads. Subsequently, NIR radiation was applied to trigger the release of the secretome. We compared the efficacy of MSCs secretome with that of astrocytes, which also possess nerve growth and proliferation-promoting capabilities. Our findings demonstrated that the controlled release of MSCs secretome from AGO microbeads through non-invasive NIR radiation significantly promoted the proliferation and regeneration of neurons following nerve injury. AGO microbeads offer multiple advantages over conventional delivery methods, including precise control over the timing, location, and dosage of therapeutic agents. Furthermore, the potential for reduced immunogenicity and tumorigenicity enhances the safety profile of the therapy. Consequently, this study presents a promising avenue for the development of MSC-based therapies for nerve regeneration, with implications for the treatment of various neuropathies and injuries.

Keywords
3D Bioprinting
Near-Infrared Radiation
Graphene Oxide
Alginate Microbeads
Neural Regeneration
Funding
Not applicable.
Conflict of interest
The authors declare no conflict of interest.
References
  1. Aktas O, Ullrich O, Infante-Duarte C, Nitsch R, Zipp F. Neuronal damage in brain inflammation. Arch Neurol. 2007;64(2):185-189. doi: 10.1001/archneur.64.2.185
  2. Tarkowski E, Liljeroth A-M, Minthon L, Tarkowski A, Wallin A, Blennow K. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull. 2003;61(3):255-260. doi: 10.1016/s0361-9230(03)00088-1
  3. White MG, Luca LE, Nonner D, et al. Cellular mechanisms of neuronal damage from hyperthermia, in Neurobiology of Hyperthermia (ed. Sharma HSBT-P). Neurobiology of Hyperthermia [Internet]. Elsevier, Prog Brain Res. 2007l;347- 371. doi: 10.1016/S0079-6123(06)62017-7
  4. Everall I, Luthert P, Lantos P. A review of neuronal damage in human immunodeficiency virus infection: Its assessment, possible mechanism and relationship to dementia. J Neuropathol Exp Neurol. 1993;52(6):561-566. doi: 10.1097/00005072-199311000-00002
  5. Guo J, Zhao X, Li Y, Li G, Liu X. Damage to dopaminergic neurons by oxidative stress in Parkinson’s disease. Int J Mol Med. 2018;41(4):1817-1825. doi: 10.3892/ijmm.2018.3406
  6. Blandini F. Neural and immune mechanisms in the pathogenesis of Parkinson’s disease. J Neuroimmune Pharmacol. 2013;8(1):189-201. doi: 10.1007/s11481-013-9435-y
  7. Perini G, Ciasca G, Minelli E, et al. Dynamic structural determinants underlie the neurotoxicity of the N-terminal tau 26-44 peptide in Alzheimer’s disease and other human tauopathies. Int J Biol Macromol. 2019;141:278-289. doi: 10.1016/j.ijbiomac.2019.08.220
  8. Zhang M, Cheng X, Dang R, Zhang W, Zhang Jie, Yao Zhongxiang. Lactate deficit in an Alzheimer disease mouse model: The relationship with neuronal damage. J Neuropathol Exp Neurol. 2018;77(12):1163-1176. doi: 10.1093/jnen/nly102
  9. Patejdl R, Zettl UK. Spasticity in multiple sclerosis: Contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions. Autoimmun Rev. 2017;16(9):925-936. doi: 10.1016/j.autrev.2017.07.004
  10. Malgouris C, Bardot F, Daniel M, et al. Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils. J Neurosci. 1989;9(11): 3720-3727. doi: 10.1523/JNEUROSCI.09-11-03720.1989
  11. Languren G, Montiel T, Julio-Amilpas A, Massieu L. Neuronal damage and cognitive impairment associated with hypoglycemia: An integrated view. Neurochem Int. 2013;63(4):331-343. doi: 10.1016/j.neuint.2013.06.018
  12. Corrigan JD, Selassie AW, Orman JAL. The epidemiology of traumatic brain injury. J Head Trauma Rehabil. 2010;25(2):72-80. doi: 10.1097/HTR.0b013e3181ccc8b4
  13. Sapolsky RM, Krey LC, McEwen BS. Prolonged glucocorticoid exposure reduces hippocampal neuron number: Implications for aging. J Neurosci. 1985;5(5):1222-1227. doi: 10.1523/JNEUROSCI.05-05-01222.198
  14. Biffi A, Capotondo A, Fasano S. et al. Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice. J Clin Invest. 2006;116(11): 3070-3082. doi: 10.1172/JCI28873
  15. Amar AP, Levy ML. Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery. 1999;44(5):1027-1039. doi: 10.1097/00006123-199905000-00052
  16. Dutta R, Trapp BD. Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology. 2007;68(22 suppl 3): S22-S31. doi: 10.1212/01.wnl.0000275229.13012.32
  17. Baron R. Peripheral neuropathic pain: From mechanisms to symptoms. Clin J Pain. 2000;16(2):S12-S20. doi: 10.1097/00002508-200006001-00004
  18. Rosenthal P, Borsook D, Moulton EA. Oculofacial pain: Corneal nerve damage leading to pain beyond the eye. Invest Ophthalmol Vis Sci. 2016;57(13):5285-5287. doi: 10.1167/iovs.16-20557
  19. Kurnellas MP, Donahue KC, Elkabes S. Mechanisms of neuronal damage in multiple sclerosis and its animal models: Role of calcium pumps and exchangers. Biochem Soc Trans. 2007;35(5):923-926. doi: 10.1042/BST0350923
  20. Zipp F, Gold R, Wiendl H. Identification of inflammatory neuronal injury and prevention of neuronal damage in multiple sclerosis: Hope for novel therapies? JAMA Neurol. 2013;70(12):1569-1574. doi: 10.1001/jamaneurol.2013.4391
  21. Meeson R, Corr S. Management of pelvic trauma: Neurological damage, urinary tract disruption and pelvic fractures. J Feline Med Surg. 2011;13(5):347-361. doi: 10.1016/j.jfms.2011.03.011
  22. Crock HV, Crock HV. The management of spinal injuries with and without neural damage. Pract Spinal Surg. 1983;281-298. doi: 10.1007/978-3-7091-3335-4_12
  23. Bechstein WO. Neurotoxicity of calcineurin inhibitors: Impact and clinical management. Transpl Int. 2000;13(5):313-326. doi: 10.1007/s001470050708
  24. Yamakami I, Yamaura A, Isobe K. Pathogenesis and management of secondary neural damage in head trauma patients: Analysis of patients who talk and deteriorate” fulminantly”. No Shinkei Geka. 1993;21(2):129-133. doi: 10.11477/mf.1436900598
  25. Bejargafshe MJ, Hedayati M, Zahabiasli S, Nejad-Moghaddam A. Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis. Stem Cell Investig. 2019;6:44. doi: 10.21037/sci.2019.10.06
  26. Wong AM, Hodges H, Horsburgh K. Neural stem cell grafts reduce the extent of neuronal damage in a mouse model of global ischaemia. Brain Res. 2005;1063(2):140-150. doi: 10.1016/j.brainres.2005.09.049
  27. Karl MO. The potential of stem cell research for the treatment of neuronal damage in glaucoma. Cell Tissue Res. 2013;353(2):311-325. doi: 10.1007/s00441-013-1646-2
  28. Qin J, Ma X, Qi HH, et al. Transplantation of induced pluripotent stem cells alleviates cerebral inflammation and neural damage in hemorrhagic stroke. PLoS One. 2015;10(6):e0129881. doi: 10.1371/journal.pone.0129881
  29. Ma X, Huang M, Zheng M, et al. ADSCs-derived extracellular vesicles alleviate neuronal damage, promote neurogenesis and rescue memory loss in mice with Alzheimer’s disease. J Control Release. 2020;327:688-702. doi: 10.1016/j.jconrel.2020.09.019
  30. Bora P, Majumdar AS. Adipose tissue-derived stromal vascular fraction in regenerative medicine: A brief review on biology and translation. Stem Cell Res Ther. 2017;8(1):145. doi: 10.1186/s13287-017-0598-y
  31. Teixeira FG, Carvalho MM, Sousa N, Salgado AJ. Mesenchymal stem cells secretome: A new paradigm for central nervous system regeneration? Cell Mol Life Sci. 2013;70:3871-3882. doi: 10.1007/s00018-013-1290-8
  32. Drago D, Cossetti C, Iraci N, et al. The stem cell secretome and its role in brain repair. Biochimie. 2013;95(12):2271-2285. doi: 10.1016/j.biochi.2013.06.020
  33. Ghasemi M, Roshandel E, Mohammadian M, et al. Mesenchymal stromal cell-derived secretome-based therapy for neurodegenerative diseases: Overview of clinical trials. Stem Cell Res Ther. 2023;14(1):1-20. doi: 10.1186/s13287-023-03264-0
  34. Carvalho M, Teixeira F, Reis R, Sousa N, Salgado AJ. Mesenchymal stem cells in the umbilical cord: phenotypic characterization, secretome and applications in central nervous system regenerative medicine. Curr Stem Cell Res Ther. 2011;6(3):221-228. doi: 10.2174/157488811796575332
  35. Martins LF, Costa RO, Pedro JR, et al. Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF. Sci Rep. 2017;7(1):4153. doi: 10.1038/s41598-017-03592-1
  36. Teixeira FG, Salgado AJ. Mesenchymal stem cells secretome: Current trends and future challenges. Neural Regen Res. 2020;15(1):75. doi: 10.4103/1673-5374.264455
  37. Kumar P, Kandoi S, Misra R, S V, K R, Verma RS. The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine. Cytokine Growth Factor Rev. 2019;46:1-9. doi: 10.1016/j.cytogfr.2019.04.002
  38. Li F, Zhang J, Yi K, Wang H, et al. Delivery of stem cell secretome for therapeutic applications. ACS Appl Bio Mater. 2022;5(5):2009-2030. doi: 10.1021/acsabm.1c01312
  39. Wechsler ME, Rao VV, Borelli AN, Anseth KS. Engineering the MSC secretome: A hydrogel focused approach. Adv Healthc Mater. 2021;10(7):2001948. doi: 10.1002/adhm.202001948
  40. Santamaria G, Brandi E, Vitola P La, et al. Intranasal delivery of mesenchymal stem cell secretome repairs the brain of Alzheimer’s mice. Cell Death Differ. 2021;28(1):203-218. doi: 10.1038/s41418-020-0592-2
  41. Shoma Suresh K, Bhat S, Guru BR, Muttigi MS, Seetharam RN. A nanocomposite hydrogel delivery system for mesenchymal stromal cell secretome. Stem Cell Res Ther. 2020;11(1):1-14. doi: 10.1186/s13287-020-01712-9
  42. Perini G, Rosenkranz A, Friggeri G, et al. Advanced usage of Ti3C2Tx MXenes for photothermal therapy on different 3D breast cancer models. Biomed Pharmacother. 2022; 153:113496. doi: 10.1016/j.biopha.2022.113496
  43. Rosenkranz A, Perini G, Aguilar-Hurtado JY, et al. Laser-mediated antibacterial effects of few- and multi-layer Ti3C2Tx MXenes. Appl Surf Sci. 2021;567:150795. doi: 10.1016/j.apsusc.2021.150795
  44. Perini G, Rosa E, Friggeri G, et al. INSIDIA 2.0 high-throughput analysis of 3D cancer models: Multiparametric quantification of graphene quantum dots photothermal therapy for glioblastoma and pancreatic cancer. Int J Mol Sci. 2022;23:3217. doi: 10.3390/ijms23063217
  45. Perini G, Palmieri V, Friggeri G, Augello A, De Spirito M, Papi M. Carboxylated graphene quantum dots-mediated photothermal therapy enhances drug-membrane permeability, ROS production, and the immune system recruitment on 3D glioblastoma models. Cancer Nanotechnol. 2023;14(1):13. doi: 10.1186/s12645-023-00168-9
  46. De Maio F, Rosa E, Perini G, et al. 3D-printed graphene polylactic acid devices resistant to SARS-CoV-2: Sunlight-mediated sterilization of additive manufactured objects. Carbon NY. 2022;194:34-41. doi: 10.1016/j.carbon.2022.03.036
  47. Choi SS, Lee HJ, Lim I, Satoh J, Kim SU. Human astrocytes: Secretome profiles of cytokines and chemokines. PLoS One. 2014;9(4):e92325. doi: 10.1371/journal.pone.0092325
  48. Skorupa A, Urbach S, Vigy O, et al. Angiogenin induces modifications in the astrocyte secretome: Relevance to amyotrophic lateral sclerosis. J Proteomics. 2013;91:274-285. doi: 10.1016/j.jprot.2013.07.028
  49. Jha MK, Seo M, Kim J-H, Kim BG, Cho JY, Suk K. The secretome signature of reactive glial cells and its pathological implications. Biochim Biophys Acta (BBA)-Proteins Proteomics. 2013;1834(11):2418-2428. doi: 10.1016/j.bbapap.2012.12.006
  50. Tanaka J, Toku K, Zhang B, Ishihara K, Sakanaka M, Maeda N. Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen species. Glia. 1999;28(2):85-96. doi: 10.1002/(sici)1098-1136(199911)28:2<85::aid-glia1>3.0.co;2-y
  51. Madrigal JLM, Leza JC, Polak P, Kalinin S, Feinstein DL. Astrocyte-derived MCP-1 mediates neuroprotective effects of noradrenaline. J Neurosci. 2009;29(1):263-267. doi: 10.1523/JNEUROSCI.4926-08.2009
  52. Pei X, Li Y, Zhu L, Zhou Z. Astrocyte-derived exosomes suppress autophagy and ameliorate neuronal damage in experimental ischemic stroke. Exp Cell Res. 2019;3 82(2):111474. doi: 10.1016/j.yexcr.2019.06.019
  53. Piacentini R, Li Puma DD, Ripoli C, et al. Herpes Simplex Virus type-1 infection induces synaptic dysfunction in cultured cortical neurons via GSK-3 activation and intraneuronal amyloid-β protein accumulation. Sci Rep. 2015;5(1):15444. doi: 10.1038/srep15444
  54. Perini G, Palmieri V, Ciasca G, et al. Graphene quantum dots’ surface chemistry modulates the sensitivity of glioblastoma cells to chemotherapeutics. Int J Mol Sci. 2020;21(17):6301. doi: 10.3390/ijms21176301
  55. Guo S, Garaj S, Bianco A, Ménard-Moyon Cécilia. Controlling covalent chemistry on graphene oxide. Nat Rev Phys. 2022;4(4):247-262. doi: 10.1038/s42254-022-00422-w
  56. Mollah MZI, Faruque MRI, Bradley DA, Khandaker MU. FTIR and rheology study of alginate samples: Effect of radiation. Radiat Phys Chem. 2023;202:110500. doi: 10.1016/j.radphyschem.2022.110500
Share
Back to top
International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept