AccScience Publishing / BH / Online First / DOI: 10.36922/bh.3996
ORIGINAL RESEARCH ARTICLE

Human dental pulp MSCs attenuated motor neuron dysfunction and prolonged lifespan in ALS murine model

Shihe Jiang1† Xiuchen Guan2† Meng Shi3 Ying Zhang1 Xindi Li1 Yingying Su3 Hao Wang3 Jian Zhou4 Fu-Dong Shi1 Songling Wang5 Wei-Na Jin1*
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1 China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
2 Department of Orthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China
3 Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
4 Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China
5 Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China
Submitted: 20 June 2024 | Accepted: 4 September 2024 | Published: 10 October 2024
© 2024 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/ )
Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that causes skeletal muscle weakness and atrophy, resulting in respiratory failure and a short lifespan. Considering the lack of effective treatment, this study investigated the effects of human dental pulp stem cells (hDPSCs) on the clinical symptoms and potential mechanisms in a mouse model of ALS superoxide dismutase 1 (SOD1-G93A). Neurological assessments, including neurological scoring, rotarod testing, and 7-T magnetic resonance imaging, were conducted to evaluate neurological impairments. Survival rates and body weight of the mice were also recorded. Immunofluorescence staining and flow cytometry analyses were performed to investigate the number of neurons and infiltrated inflammatory cells in the spinal cord as well as the central nervous system. The results indicate that infusion of hDPSCs increased the body weight, mitigated motor neuron dysfunction, and extended the lifespan of SOD1-G93A mice by approximately 15 days. Moreover, hDPSCs infusion reduced the degree of spinal cord atrophy. Results suggested that the number of neurons in the central nervous system of SOD1-G93A mice was significantly decreased, but hDPSCs infusion resulted in an increase in these numbers. However, hDPSCs infusion had no obvious effect on microglia phenotypes in SOD1-G93A mice. This study emphasizes the potential of hDPSCs to mitigate neuronal loss in an ALS mouse model, suggesting a promising therapeutic avenue for ALS.

Keywords
Human dental pulp stem cells
Amyotrophic lateral sclerosis
Neurons
Inflammation
Murine model
Funding
This work was supported in part by the National Science Foundation of China (82122021).
Conflict of interest
Wei-Na Jin is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
References
  1. Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: Models, mechanisms, and a new hope. Dis Model Mech. 2017;10(5):499-502. doi: 10.1242/dmm.030205

 

  1. Mehta P, Raymond J, Punjani R, et al. Prevalence of Amyotrophic Lateral Sclerosis (ALS), United States, 2016. Amyotroph Lateral Scler Frontotemporal Degener. 2022;23(3-4):220-225. doi: 10.1080/21678421.2021.1949021

 

  1. Longinetti E, Fang F. Epidemiology of amyotrophic lateral sclerosis: An update of recent literature. Curr Opin Neurol. 2019;32(5):771-776. doi: 10.1097/wco.0000000000000730

 

  1. Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017;377(2):162-172. doi: 10.1056/NEJMra1603471

 

  1. Batagov AO, Kurochkin IV. Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3’-untranslated regions. Biology Direct. 2013;8:12. doi: 10.1186/1745-6150-8-12

 

  1. Kiernan MC, Vucic S, Cheah BC, et al. Amyotrophic lateral sclerosis. Lancet. 2011;377(9769):942-955. doi: 10.1016/s0140-6736(10)61156-7

 

  1. Bruijn LI, Houseweart MK, Kato S, et al. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science. 1998;281(5384):1851-1854. doi: 10.1126/science.281.5384.1851

 

  1. Oskarsson B, Gendron TF, Staff NP. Amyotrophic lateral sclerosis: An update for 2018. Mayo Clin Proc. 2018;93(11):1617-1628. doi: 10.1016/j.mayocp.2018.04.007

 

  1. Brooks BR, Berry JD, Ciepielewska M, et al. Intravenous edaravone treatment in ALS and survival: An exploratory, retrospective, administrative claims analysis. EClinicalMedicine. 2022;52:101590. doi: 10.1016/j.eclinm.2022.101590

 

  1. Ford E, Pearlman J, Ruan T, et al. Human pluripotent stem cells-based therapies for neurodegenerative diseases: Current status and challenges. Cells. 2020;9(11):2517. doi: 10.3390/cells9112517

 

  1. De Gioia R, Biella F, Citterio G, et al. Neural stem cell transplantation for neurodegenerative diseases. Int J Mol Sci. 2020;21(9):3103. doi: 10.3390/ijms21093103

 

  1. Wang D, Wang Y, Tian W, Pan J. Advances of tooth-derived stem cells in neural diseases treatments and nerve tissue regeneration. Cell Prolif. 2019;52(3):e12572. doi: 10.1111/cpr.12572

 

  1. Horwitz EM, Le Blanc K, Dominici M, et al. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 2005;7(5):393-395. doi: 10.1080/14653240500319234

 

  1. Kim C, Lee HC, Sung JJ. Amyotrophic lateral sclerosis - Cell based therapy and novel therapeutic development. Exp Neurobiol. 2014;23(3):207-214. doi: 10.5607/en.2014.23.3.207

 

  1. Mortada I, Mortada R, Al Bazzal M. Dental pulp stem cells and neurogenesis. Adv Exp Med Biol. 2018;1083:63-75. doi: 10.1007/5584_2017_71

 

  1. Nuti N, Corallo C, Chan BMF, Ferrari M, Gerami-Naini B. Multipotent differentiation of human dental pulp stem cells: A literature review. Stem Cell Rev Rep. 2016;12(5):511-523. doi: 10.1007/s12015-016-9661-9

 

  1. De Almeida FM, Marques SA, Ramalho Bdos S, et al. Human dental pulp cells: A new source of cell therapy in a mouse model of compressive spinal cord injury. J Neurotrauma. 2011;28(9):1939-1949. doi: 10.1089/neu.2010.1317

 

  1. Crende O, García-Gallastegui P, Luzuriaga J, et al. Is there such a thing as a genuine cancer stem cell marker? Perspectives from the gut, the brain and the dental pulp. Biology (Basel). 2020;9(12):426. doi: 10.3390/biology9120426

 

  1. Hollands P, Aboyeji D, Orcharton M. Dental pulp stem cells in regenerative medicine. Br Dent J. 2018; 224:747-750. doi: 10.1038/sj.bdj.2018.348

 

  1. Guégan C, Vila M, Rosoklija G, Hays AP, Przedborski S. Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic lateral sclerosis. J Neurosci. 2001;21(17):6569-6576. doi: 10.1523/jneurosci.21-17-06569.2001

 

  1. Sartoretti T, Ganley RP, Ni R, Freund P, Zeilhofer HU, Klohs J. Structural MRI reveals cervical spinal cord atrophy in the P301L mouse model of tauopathy: Gender and transgene-dosing effects. Front Aging Neurosci. 2022;14:825996. doi: 10.3389/fnagi.2022.825996

 

  1. Chen H, Kankel MW, Su SC, Han SWS, Ofengeim D. Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD. Cell Death Differ. 2018;25(4):648-662. doi: 10.1038/s41418-018-0060-4

 

  1. Jo CH, Lee YG, Shin WH, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: A proof-of-concept clinical trial. Stem Cells. 2014;32(5):1254-1266. doi: 10.1002/stem.1634

 

  1. Bartolucci J, Verdugo FJ, Gonzalez PL, et al. Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: A Phase 1/2 randomized controlled trial (RIMECARD trial [Randomized clinical trial of intravenous infusion umbilical cord mesenchymal stem cells on cardiopathy]). Circ Res. 2017;121(10):1192-1204. doi: 10.1161/CIRCRESAHA.117.310712

 

  1. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human Dental Pulp Stem Cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000;97(25):13625-13630. doi: 10.1073/pnas.240309797

 

  1. Huang GTJ, Gronthos S, Shi S. Mesenchymal stem cells derived from dental tissues vs. Those from other sources: Their biology and role in regenerative medicine. J Dent Res. 2009;88(9):792-806. doi: 10.1177/0022034509340867

 

  1. Magota H, Sasaki M, Kataoka-Sasaki Y, et al. Repeated infusion of mesenchymal stem cells maintain the condition to inhibit deteriorated motor function, leading to an extended lifespan in the SOD1G93A rat model of amyotrophic lateral sclerosis. Mol Brain. 2021;14(1):76. doi: 10.1186/s13041-021-00787-6

 

  1. Magota H, Sasaki M, Kataoka-Sasaki Y, et al. Intravenous infusion of mesenchymal stem cells delays disease progression in the SOD1G93A transgenic amyotrophic lateral sclerosis rat model. Brain Res. 2021;1757:147296. doi: 10.1016/j.brainres.2021.147296

 

  1. Hosokawa M, Arai T, Yamashita M, et al. Differential diagnosis of amyotrophic lateral sclerosis from Guillain- Barré syndrome by quantitative determination of TDP-43 in cerebrospinal fluid. Int J Neurosci. 2014;124(5):344-349. doi: 10.3109/00207454.2013.848440

 

  1. Nosrat IV, Smith CA, Mullally P, Olson L, Nosrat CA. Dental pulp cells provide neurotrophic support for dopaminergic neurons and differentiate into neurons in vitro; Implications for tissue engineering and repair in the nervous system. Eur J Neurosci. 2004;19(9):2388-2398. doi: 10.1111/j.0953-816X.2004.03314.x

 

  1. Magazzù A, Marcuello C. Investigation of soft matter nanomechanics by atomic force microscopy and optical tweezers: A comprehensive review. Nanomaterials (Basel). 2023;13(6):963. doi: 10.3390/nano13060963

 

  1. Wei X, Yang M, Yue L, et al. Expert consensus on regenerative endodontic procedures. Int J Oral Sci. 2022;14(1):55. doi: 10.1038/s41368-022-00206-z

 

  1. Hata M, Omi M, Kobayashi Y, et al. Transplantation of human dental pulp stem cells ameliorates diabetic polyneuropathy in streptozotocin-induced diabetic nude mice: The role of angiogenic and neurotrophic factors. Stem Cell Res Ther. 2020;11(1):236. doi: 10.1186/s13287-020-01758-9

 

  1. Luzuriaga J, Polo Y, Pastor-Alonso O, et al. Advances and perspectives in dental pulp stem cell based neuroregeneration therapies. Int J Mol Sci. 2021;22(7):3546. doi: 10.3390/ijms22073546

 

  1. Bar JK, Lis-Nawara A, Grelewski PG. Dental pulp stem cell-derived secretome and its regenerative potential. Int J Mol Sci. 2021;22(21):12018. doi: 10.3390/ijms222112018

 

  1. Leong WK, Henshall TL, Arthur A, et al. Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms. Stem Cells Transl Med. 2012;1(3):177-187. doi: 10.5966/sctm.2011-0039

 

  1. Zhang Z, Zou X, Zhang R, et al. Human umbilical cord mesenchymal stem cell-derived exosomal miR-146a-5p reduces microglial-mediated neuroinflammation via suppression of the IRAK1/TRAF6 signaling pathway after ischemic stroke. Aging (Albany NY). 2021;13(2):3060-3079. doi: 10.18632/aging.202466

 

  1. Liu YY, Li Y, Wang L, et al. Mesenchymal stem cell-derived exosomes regulate phenotypes: A promising treatment for acute central nervous system injury. Neural Regen Res. 2023;18(8):1657-1665. doi: 10.4103/1673-5374.363819
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Brain & Heart, Electronic ISSN: 2972-4139 Published by AccScience Publishing