Volume 25, Issue 3 (Iranian South Medical Journal 2022)
Iran South Med J 2022, 25(3): 227-239 |
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Kousha A, Haji Ghasem Kashani M, Vaezi G H, Hojati V. Expression of Neurotrophins in Adipose-derived Stem Cells during in vitro Culture and Posttransplantation in Parkinsonian Rat Model. Iran South Med J 2022; 25 (3) :227-239
URL: http://ismj.bpums.ac.ir/article-1-1626-en.html
URL: http://ismj.bpums.ac.ir/article-1-1626-en.html
1- Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
2- Department of Cellular and Molecular, School of Biology, Damghan University, Damghan, Iran ,kashani@du.ac.ir
2- Department of Cellular and Molecular, School of Biology, Damghan University, Damghan, Iran ,
Abstract: (1334 Views)
Background: Adipose tissue stem cells (ASCs) cause faster repair of damaged tissue posttransplantation by releasing growth factors in neurodegenerative diseases. ASCs secrete factors in the culture medium called conditioned medium (CM) in vitro. This study investigated the expression of neurotrophin genes in vitro culture and transplant of ASCs in Parkinsonian rats.
Materials and Methods: In this study, expression of neurotrophin genes was investigated in vitro and in vivo. In vitro means evaluating expression of genes in the conditioned medium from 21-day culture of ASCs (culture group) and the transplantation group, which were divided into subgroups of Parkinsonian rat model receiving ASCs (Cell group), and another group reveiving cells and conditioned medium (Cell + Conditioned Medium group). The sham groups were designed with Parkinsonian model and sham animals injected respectively with 6-OHDA (neurotoxin) and normal saline (neurotoxin solvent) instead of neurotoxin. All the injections were performed stereotaxically into the right striatum. After eight weeks of treatment, the transplantation areas were isolated and stored at -70 °C. Then, the exression of neurotrophin (BDNF, NT3 and NGF) mRNAs was analyzed.
Results: BDNF and NT3 mRNA expression levels were significantly higher in the cells+conditioned medium and cell, as compared with the culture group. A significant decrease in NT3 gene expression in cell group was observed compared to that of cell group + conditional medium. NGF expression of the culture and cell groups showed a significant decrease compared to the cell+conditional medium group.
Conclusion: In vitro cultured ASCs cannot significantly induce expression of neurotrophin genes, but when the cells are transplanted along with secretions (conditional medium) at the site of injury, the microenvironment of the transplantation site can induce higher expressions of neurotrophins. These cells will be good candidates for cell therapy.
Materials and Methods: In this study, expression of neurotrophin genes was investigated in vitro and in vivo. In vitro means evaluating expression of genes in the conditioned medium from 21-day culture of ASCs (culture group) and the transplantation group, which were divided into subgroups of Parkinsonian rat model receiving ASCs (Cell group), and another group reveiving cells and conditioned medium (Cell + Conditioned Medium group). The sham groups were designed with Parkinsonian model and sham animals injected respectively with 6-OHDA (neurotoxin) and normal saline (neurotoxin solvent) instead of neurotoxin. All the injections were performed stereotaxically into the right striatum. After eight weeks of treatment, the transplantation areas were isolated and stored at -70 °C. Then, the exression of neurotrophin (BDNF, NT3 and NGF) mRNAs was analyzed.
Results: BDNF and NT3 mRNA expression levels were significantly higher in the cells+conditioned medium and cell, as compared with the culture group. A significant decrease in NT3 gene expression in cell group was observed compared to that of cell group + conditional medium. NGF expression of the culture and cell groups showed a significant decrease compared to the cell+conditional medium group.
Conclusion: In vitro cultured ASCs cannot significantly induce expression of neurotrophin genes, but when the cells are transplanted along with secretions (conditional medium) at the site of injury, the microenvironment of the transplantation site can induce higher expressions of neurotrophins. These cells will be good candidates for cell therapy.
Type of Study: Original |
Subject:
Nervous System
Received: 2022/07/28 | Accepted: 2022/09/19 | Published: 2022/09/22
Received: 2022/07/28 | Accepted: 2022/09/19 | Published: 2022/09/22
References
1. Chan TM, Chen JY, Ho LI, et al. ADSC therapy in neurodegenerative disorders. Cell Transplant 2014; 23(4-5): 549-57. [DOI]
2. Chen L, Qiu R, Xu Q. Mesenchymal stem cell therapy for neurodegenerative diseases. J Nanosci Nanotechnol 2014; 14(1): 969-75. [DOI]
3. Zakrzewski W, Dobrzyński M, Szymonowicz M, et al. Stem cells: past, present, and future. Stem Cell Res Ther 2019; 10(1): 68. [DOI]
4. Mousaei Ghasroldasht M, Seok J, Park H-S, et al. Stem cell therapy: From idea to clinical practice. Int J Mol Sci 2022; 23(5): 2850. [DOI]
5. Zhang J, Liu Y, Chen Y, et al. Adipose-derived stem cells: current applications and future directions in the regeneration of multiple tissues. Stem Cells Int 2020; 2020: 8810813. [DOI]
6. Glavaski-Joksimovic A, Bohn MC. Mesenchymal stem cells and neuroregeneration in Parkinson's disease. Exp Neurol 2013; 247: 25-38. [DOI]
7. Elsworth JD. Parkinson's disease treatment:past, present, and future. J Neural Transm (Vienna) 2020; 127(5): 785-791. [DOI]
8. Barbuti PA, Barker RA, Brundin P, et al. Recent Advances in the Development of Stem Cell-Derived Dopaminergic Neuronal Transplant Therapies for Parkinson's Disease. Mov Disord 2021; 36(8): 1772-1780. [DOI]
9. Liu Z, Cheung H-H. Stem cell-based therapies for Parkinson disease. Int J Mol Sci 2020; 21(21): 8060. [DOI]
10. Panicker N, Dawson VL, Dawson TM. The cell biology of Parkinson’s disease. J Cell Biol 2021; 220(4): e202012095. [DOI]
11. Mustapha M, Mat Taib CN. MPTP-induced mouse model of Parkinson's disease: A promising direction of therapeutic strategies. Bosn J Basic Med Sci 2021; 21(4): 422-433. [DOI]
12. Mendes-Pinheiro B, Anjo SI, Manadas B, et al. Bone marrow mesenchymal stem cells' secretome exerts neuroprotective effects in a Parkinson's disease rat model. Front Bioeng Biotechnol 2019; 7: 294. [DOI]
13. Torrente Y, Polli E. Mesenchymal stem cell transplantation for neurodegenerative diseases. Cell Transplant 2008; 17(10-11): 1103-13. [DOI]
14. L PK, Kandoi S, Misra R, et al. 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]
15. Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res Int 2014; 2014: 965849. [DOI]
16. Gunawardena TNA, Rahman MT, Abdullah BJJ, et al. Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine. J Tissue Eng Regen Med 2019; 13(4): 569-86. [DOI]
17. Xu R, Wu J, Lang L, et al. Implantation of glial cell line-derived neurotrophic factor-expressing adipose tissue-derived stromal cells in a rat Parkinson’s disease model. Neurol Res 2020; 42(8): 712-20. [DOI]
18. Allen SJ, Watson JJ, Shoemark DK, et al. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 2013; 138(2): 155-75. [DOI]
19. Ruozi B, Belletti D, Bondioli L, et al. Neurotrophic factors and neurodegenerative diseases: a delivery issue. Int Rev Neurobiol 2012; 102: 207-47. [DOI]
20. Ibrahim AM, Chauhan L, Bhardwaj A, et al. Brain-Derived Neurotropic Factor in Neurodegenerative Disorders. BioMed 2022;10(5):1143. [DOI]
21. Binder DK. Neurotrophins in the dentate gyrus. Prog Brain Res 2007; 163: 371-97. [DOI]
22. Tome D, Fonseca CP, Campos FL, et al. Role of Neurotrophic Factors in Parkinson's Disease. Curr Pharm Des 2017; 23(5): 809-838. [DOI]
23. Collier TJ, Sortwell CE.Therapeutic potential of nerve growth factors in Parkinson's disease. Drugs Aging 1999; 14(4): 261-87. [DOI]
24. Mahendru D, Jain A, Bansal S, et al. Neuroprotective effect of bone marrow-derived mesenchymal stem cell secretome in 6-OHDA-induced Parkinson's disease. Regen Med 2021; 16(10): 915-30. [DOI]
25. Kim HJ, Lee JH, Kim SH. Therapeutic effects of human mesenchymal stem cells on traumatic brain injury in rats: secretion of neurotrophic factors and inhibition of apoptosis. J Neurotrauma 2010; 27(1): 131-8. [DOI]
26. Trzyna A, Banaś-Ząbczyk A. Adipose-derived stem cells secretome and its potential application in “stem cell-free therapy”. Biomolecules 2021;11(6):878. [DOI]
27. Nakhaeifard M, Kashani MHG, Goudarzi I, et al. Conditioned medium protects dopaminergic neurons in parkinsonian rats. Cell J 2018; 20(3): 348-354. [DOI]
28. Munoz JR, Stoutenger BR, Robinson AP, et al. Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proc Natl Acad Sci USA 2005; 102(50): 18171-6. [DOI]
29. Hoban DB, Howard L, Dowd E. GDNF-secreting mesenchymal stem cells provide localized neuroprotection in an inflammation-driven rat model of Parkinson’s disease. Neuroscience 2015; 303: 402-11. [DOI]
30. Wei X, Du Z, Zhao L, et al. IFATS collection: the conditioned media of adipose stromal cells protect against hypoxia-ischemiainduced brain damage in neonatal rats. Stem cells 2009; 27(2): 478-88. [DOI]
31. Gu H, Wang J, Du N, et al. Adipose stromal cells-conditioned medium blocks 6- hydroxydopamine-induced neurotoxicity and reactive oxygen species. Neurosci Lett 2013; 544: 15-9. [DOI]
32. Noverina R, Widowati W, Ayuningtyas W, et al. Growth factors profile in conditioned medium human adipose tissue-derived mesenchymal stem cells (CM-hATMSCs). Clin Nutr Expert 2019; 24: 34-44. [Article]
33. Betarbet R, Sherer TB, Greenamyre JT. Animal models of Parkinson's disease. Bioessays 2002; 24(4): 308-18. [DOI]
34. Larsson E, Nanobashvili A, Kokaia Z, et al. Evidence for neuroprotective effects of endogenous brain-derived neurotrophic factor after global forebrain ischemia in rats. J Cereb Blood Flow Metab 1999; 19(11): 1220-8. [DOI]
35. Molinari C, Morsanuto V, Ruga S, et al. The Role of BDNF on Aging-Modulation Markers. Brain Sci 2020; 10(5): 285. [DOI]
36. Bondarenko O, Saarma M. Neurotrophic Factors in Parkinson's Disease: Clinical Trials, Open Challenges and Nanoparticle-Mediated Delivery to the Brain. Front Cell Neurosci 2021; 15: 682597. [DOI]
37. Möller JC, Sautter J, Kupsch A. Potential of neurotrophic factors in therapy of Parkinson's disease. J Neural Transm Suppl 1996; 48: 103-12. [DOI]
38. Zare MA, Baghaban Eslaminejad MR, Hosseini A. Study of mesenchymal stem cells derived from human umbilical cord vein wall and determining the process of differentiation to cartilage and bone. Iran South Med J 2015, 17(6): 1135-1142. [Article]
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