Adipose-Derived Mesenchymal Stem Cell (AD-MSC)-Like Cells Restore Nestin Expression and Reduce Amyloid Plaques in Aluminum Chloride (AlCl3)-Driven Alzheimer's Rat Models
Abstract
Background: Alzheimer's disease (AD) is a neurodegenerative disorder with a significant burden on public health, and current treatments offer limited efficacy. This study investigated the effectiveness of adipose-derived mesenchymal stem cells (AD-MSCs) on the expression of the nestin gene and amyloid plaque in an aluminum chloride (AlCl3)-driven Alzheimer's rat model.
Materials and methods: AD-MSCs were characterized using flow cytometry. Adult male Wistar rats were treated with/without AlCl3 and injected with/without AD-MSCs. After 5 days of AlCl3 ingestion and 4 weeks of subsequent AD-MSCs intraperitoneal injection, behavioral and molecular assessments were conducted. The Y-maze alternation test was used to test spatial learning of rats. Nestin gene expression was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The presence of amyloid plaque in the cortex and the hippocampus was evaluated through Congo red staining.
Results: AD-MSC-like cells expressed the MSC markers CD90, CD73 and CD105. The Y-maze alternation result for rats treated with AlCl3 and AD-MSC-like cells was significantly higher compared with rats treated with AlCl3 only. Nestin gene expression was significantly higher in rats treated with AlCl3 and AD-MSC-like cells compared to those treated with AlCl3 only. After AD-MSC-like cells treatment, the Congo red staining results of rat’s cortex and hippocampus were significantly decreased.
Conclusion: The findings suggest that AD-MSC-like cells possess therapeutic potential in restoring neural plasticity, amyloid plaque clearance and warrant further investigation for AD treatment. This study contributes to the emerging field of stem cell therapy for neurodegenerative diseases by highlighting the promise of AD-MSCs.
Keywords: Alzheimer's disease, adipose-derived mesenchymal stem cells, neural plasticity, congo red staining, stem cell therapy
Full Text:
PDFReferences
Hu J, Wang X. Alzheimer's disease: From pathogenesis to mesenchymal stem cell therapy - Bridging the missing link. Front Cell Neurosci. 2022; 15: 811852, CrossRef.
Gao G, Li C, Ma Y, Liang Z, Li Y, Li X, et al. Neural stem cell-derived extracellular vesicles mitigate Alzheimer's disease-like phenotypes in a preclinical mouse model. Signal Transduct Target Ther. 2023; 8(1):3-6, CrossRef.
Qin C, Wang K, Zhang L, Bai L. Stem cell therapy for Alzheimer's disease: An overview of experimental models and reality. Anim Model Exp Med. 2022; 5(1):15-26, CrossRef.
Promyo K, Iqbal F, Chaidee N, Chetsawang B. Aluminum chloride-induced amyloid β accumulation and endoplasmic reticulum stress in rat brain are averted by melatonin. Food Chem Toxicol. 2020; 146: 111829, CrossRef.
Rondeau V, Commenges D, Jacqmin-Gadda H, Dartiques J. Relation between aluminium concentrations in drinking water and Alzheimer's disease: An 8-year follow-uo study. Am J Epidemiol. 2000; 152(1): 59-66, CrossRef.
Kawahara M, Kato-Negishi M. Link between aluminum and the pathogenesis of Alzheimer's disease: The integration of the aluminum and amyloid cascade hypotheses. Int J Alzheimers Dis. 2011; 2011: 27639, CrossRef.
Lina Y, Wijaya A. Adipose-derived stem cells for future regenerative system medicine. Indones Biomed J. 2012; 4(2): 59-72, CrossRef.
Bali P, Lahiri DK, Banik A, Nehru B, Anand A. Potential for stem cells therapy in Alzheimer's disease: Do neurotrophic factors play critical role? Curr Alzheimer Res. 2017; 14(2): 208-20, CrossRef.
Yu S, Hei Y, Liu W. Upregulation of seladin-1 and nestin expression in bone marrow mesenchymal stem cell transplantation via the ERK1/2 and PI3K/Akt signaling pathways in an Alzheimer's disease model. Oncol Lett. 2018; 15(5): 7443-9, CrossRef.
Zeng Q, Zheng M, Zhang T, He G. Hippocampal neurogenesis in the APP/PS1/nestin-GFP triple transgenic mouse model of Alzheimer's disease. Neuroscience. 2016; 314: 64-74, CrossRef.
Chung CS, Fujita N, Kawahara N, Yui S, Nam E, Nishimura R. A comparison of neurosphere differentiation potential of canine bone marrow-derived mesenchymal stem cells and adipose-derived mesenchymal stem cells. J Vet Med Sci. 2013; 75(7): 879-86, CrossRef.
Abshenas R, Artimani T, Shahidi S, Ranjbar A, Komaki A, Salehi I, et al. Treadmill exercise enhances the promoting effects of preconditioned stem cells on memory and neurogenesis in Aβ-induced neurotoxicity in the rats. Life Sci. 2020; 249: 117482, CrossRef.
Annita A, Revilla G, Ali H, Almurdi A. Exploring the effects of bone marrow mesenchymal stem cells on amyloid plaque reduction in a rat model of Alzheimer ' s disease. 2023; 46(6): 1036-44, article.
Ali H, Tjong DH, Yarni SD. Gene expression of caspase-9 and calm1 in rat models of Alzheimer's disease after addition mesenchymal stem cell wharton jelly. In: Jamsari, Nova B, Oktavioni M, editors. AIP Conference Proceedings: 3rd International Conference of Bio-Based Economy for Application and Utility 2021 Nov 10, Padang. AIP Publishing; 2023. 2730(1): 060004, CrossRef.
Fiolin J, Dilogo IH, Antarianto RD, Pontoh LA. Isolation and characterization of adipose-derived mesenchymal stem cell exosomes: An in-vitro study. J Prof Medika. 2022; 16(2): 108-12, CrossRef.
Harsan H, Mariya S, Islam AA, Wahjoepramono EJ, Yusuf I. Isolation of mesenchymal stem cells from adipose tissue. Indones Biomed J. 2015; 7(3): 153-6, CrossRef.
Waldau B, Shetty AK. Behavior of neural stem cells in the Alzheimer brain. Cell Mol Life Sci. 2008; 65(15): 2372-84, CrossRef.
Song S, Song S, Zhang H, Cuevas J, Sanchez-Ramos J. Comparison of neuron-like cells derived from bone marrow stem cells to those differentiated from adult brain neural stem cells. Stem Cells Dev. 2007; 16(5): 747-56, CrossRef.
Lee M, Ban J, Yang S, Im W, Kim M. The exosome of adiposederived stem cells reduces beta-amyloid pathology and apoptosis of neuronal cells derived from the transgenic mouse model of Alzheimer's disease. Brain Res. 2018; 1691: 87-93, CrossRef.
Zenchak JR, Palmateer B, Dorka N, Brown TM, Wagner L-M, Medendorp WE, et al. Bioluminescence-driven optogenetic activation of transplanted neural precursor cells improves motor deficits in a Parkinson's disease mouse model. J Neurosci Res. 2020; 98(3): 458-68, CrossRef.
Kim S, Chang KA, Kim Ja, Park HG, Ra JC, Kim HS, et al. The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer's disease mice. Plos One. 2012; 7(9): e45757, CrossRef.
Ferroni L, Gardin C, Tocco I, Epis R, Casadei A, Vindigni V, et al. Potential for neural differentiation of mesenchymal stem cells. Adv Biochem Eng Biotechnol. 2013; 129: 89-115, CrossRef.
Chun SY, Lim JO, Lee EH, Han MH, Ha YS, Lee JN, et al. Preparation and characterization of human adipose tissue-derived extracellular matrix, growth factors, and stem cells: A concise review. Tissue Eng Regen Med. 2019; 16(4): 385-93, CrossRef.
Feng Z, Zhao G, Yu L. Neural stem cells and Alzheimer's disease: Challenges and hope. Am J Alzheimers Dis Other Demen. 2009; 24(1): 52-7, CrossRef.
Ayoub S, Berbéri A, Fayyad-Kazan M. An update on human periapical cyst-mesenchymal stem cells and their potential applications in regenerative medicine. Mol Biol Rep. 2020; 47(3): 2381-9, CrossRef.
Bassiony HS, Zickri MB, Metwally HG, Elsherif HA, Alghandour SM, Sakr W. Comparative histological study on the therapeutic effect of green tea and stem cells in Alzheimer's disease complicating experimentally induced diabetes. Int J Stem Cells. 2015; 8(2): 181-90, CrossRef.
Choi SH, Tanzi RE. Is alzheimer's disease a neurogenesis disorder? Cell Stem Cell. 2019; 25(1): 7-8,
Walker KA, Ficek BN, Westbrook R. Understanding the role of systemic inflammation in Alzheimer's disease. ACS Chem Neurosci. 2019; 10(8): 3340-2, CrossRef.
Cho YJ, Song HS, Bhang S, Lee S, Kang BG, Lee JC, et al. Therapeutic effects of human adipose stem cell-conditioned medium on stroke. J Neurosci Res. 2012; 90(9): 1794-802, CrossRef.
Lopez-Toledano MA, Ali Faghihi M, Patel NS, Wahlestedt C. Adult neurogenesis: A potential tool for early diagnosis in Alzheimer's disease? J Alzheimer's Dis. 2010; 20(2): 395-408, CrossRef.
Si Z, Wang X. Stem cell therapies in Alzheimer's disease: Applications for Disease Modeling. J Pharmacol Exp Ther. 2021; 377(2): 207-17, CrossRef.
Aminizadeh N, Tiraihi T, Mesbah-Namin SA, Taheri T. A comparative study of the effects of sodium selenite and glutathione mono ethyl ester on aged adipose-derived stem cells: The telomerase and cellular responses. Rejuvenation Res. 2018; 21(1): 29-36, CrossRef.
Olayinka O, Olayinka OO, Alemu BT, Akpinar-Elci M, Grossberg GT. Toxic environmental risk factors for Alzheimer's disease: A systematic review. Aging Med Healthc. 2019; 10(1): 4-17, CrossRef.
Frost GR, Jonas LA, Li YM. Friend, Foe or Both? Immune Activity in Alzheimer's Disease. Front Aging Neurosci. 2019; 11: 337, CrossRef.
Kwon S, Yoo KH, Sym SJ, Khang D. Mesenchymal stem cell therapy assisted by nanotechnology: A possible combinational treatment for brain tumor and central nerve regeneration. Int J Nanomedicine. 2019; 14: 5925-42, CrossRef.
Ahmeda HH, Shoushab WG, Mahdyb ES, Rashedc LA, Abdob SM. Influence of adipose tissue derived mesenchymal stem cells in combination with injectable bone substitute on osteoclastogenesis in osteoporotic rats. J Appl Pharm Sci. 2013; 3(8): 46-56, CrossRef.
Bernal A, Arranz L. Nestin-expressing progenitor cells: Function, identity and therapeutic implications. Cell Mol Life Sci. 2018; 75(12): 2177-95, CrossRef.
Darmayanti S, Triana R, Chouw A, Dewi NM. Is stem cell a curer or an obstruction? Mol Cell Biomed Sci. 2017; 1(1): 17-27, CrossRef.
DOI: https://doi.org/10.21705/mcbs.v8i3.387
Copyright (c) 2024 Cell and BioPharmaceutical Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
Cell and BioPharmaceutical Institute