Abstract
Elderly people whose daily activities have declined due to a cerebrovascular disorder may suffer from dysphagia and may find oral hygiene difficult. Therefore, it is important to establish an effective therapy for the underlying cerebrovascular disorder. Dedifferentiated fat cells (DFAT) were obtained from mature adipocytes isolated from human buccal adipose pads in a ceiling culture. DFAT expressed the neural markers Nestin and SOX2. Flow cytometric analysis revealed that the cells had properties similar to mesenchymal stem cells. Although the transplantation of DFAT did not change the infarction area and volume ratios in a murine cerebral infarction model, functional recovery was observed in behavioral tests. Furthermore, DFAT administered to mice were later detected in cerebral infarctions. It therefore appears that transplanted DFAT affect the brain after infarction and contribute to the promotion of functional recovery. This finding may provide new cell replacement therapy options for treating disorders of the central nervous system.
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References
Argibay B, Trekker J, Himmelreich U, Beiras A, Topete A, Taboada P, Pérez-Mato M, Vieites-Prado A, Iglesias-Rey R, Rivas J et al (2017) Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia. Sci Rep. https://doi.org/10.1038/srep40758
Bang OY, Lee JS, Lee PH, Lee G (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882. https://doi.org/10.1002/ana.20501
Chen X, Li Y, Wang L, Lu M, Zhang X, Chopp M (2001) Therapeutic benefit of intracerebral ischemia in rat. J Neurol Sci 189:49–57. https://doi.org/10.1016/S0022-510X(01)00557-3
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Dj Prockop, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317. https://doi.org/10.1080/14653240600855905
Gutiérrez-Fernández M, Rodríguez-Frutos B, Otero-Ortega L, Ramos-Cejudo J, Fuentes B, Díez-Tejedor E (2013a) Adipose tissue-derived stem cells in stroke treatment: from bench to bedside. Discov Med 16:37–43
Gutiérrez-Fernández M, Rodríguez-Frutos B, Ramos-Cejudo J, Teresa Vallejo-Cremades M, Fuentes B, Cerdán S, Díez-Tejedor E (2013b) Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke. Stem Cell Res Ther 4:11. https://doi.org/10.1186/scrt159
Ikegame Y, Yamashita K, Hayashi S, Mizuno H, Tawada M, You F, Yamada K, Tanaka Y, Egashira Y, Nakashima S et al (2011) Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy. Cytotherapy 13:675–685. https://doi.org/10.3109/14653249.2010.549122
Kishimoto N, Momota Y, Hashimoto Y, Tatsumi S, Ando K, Omasa T, Kotani J (2014) The osteoblastic differentiation ability of human dedifferentiated fat cells is higher than that of adipose stem cells from the buccal fat pad. Clin Oral Investig 18:1893–1901. https://doi.org/10.1007/s00784-013-1166-1
Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y, Kato K et al (2004) BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model. Mol Ther 9:189–197. https://doi.org/10.1016/j.ymthe.2003.10.012
Kurozumi K, Nakamura K, Tamiya T, Kawano Y, Ishii K, Kobune M, Hirai S, Uchida H, Sasaki K, Ito Y et al (2005) Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model. Mol Ther 11:96–104. https://doi.org/10.1016/j.ymthe.2004.09.020
Matsumoto T, Kano K, Kondo D, Fukuda N, Iribe Y, Tanaka N, Matsubara Y, Sakuma T, Satomi A, Otaki M et al (2008) Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 215:210–222. https://doi.org/10.1002/jcp.21304
Nakagomi N, Nakagomi T, Kubo S, Nakano-Doi A, Saino O, Takata M, Yoshikawa H, Stern D, Matsuyama T, Taguchi A (2009a) Endothelial cells support survival, proliferation, and neuronal differentiation of transplanted adult ischemia-induced neural stem/progenitor cells after cerebral infarction. Stem Cells 27:2185–2195
Nakagomi T, Taguchi A, Fujimori Y, Saino O, Nakano-Doi A, Kubo S, Gotoh A, Soma T, Yoshikawa H, Nishizaki T et al (2009b) Isolation and characterization of neural stem/progenitor cells from post-stroke cerebral cortex in mice. Eur J Neurosci 29:1842–1852. https://doi.org/10.1111/j.1460-9568.2009.06732.x
Nakata M, Nakagomi T, Maeda M, Nakano-Doi A, Momota Y, Matsuyama T (2017) Induction of perivascular neural stem cells and possible contribution to neurogenesis following transient brain ischemia/reperfusion injury. Transl Stroke Res 8:131–143. https://doi.org/10.1007/s12975-016-0479-1
Ohta Y, Takenaga M, Tokura Y, Hamaguchi A, Matsumoto T, Kano K, Mugishima H, Okano H, Igarashi R (2008) Mature adipocyte-derived cells, dedifferentiated fat cells (DFAT), promoted functional recovery from spinal cord injury-induced motor dysfunction in rat. Cell Transplant 17:877–886. https://doi.org/10.3727/096368908786576516
Patricia AZ, Min Z, Peter A, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295. https://doi.org/10.1091/mbc.e02-02-0105
Poloni A, Maurizi G, Foia F, Mondini E, Mattiucci D, Ambrogini P, Lattanzi D, Mancini S, Falconi M, Cinti S et al (2015) Glial-like differentiation potential of human mature adipocytes. J Mol Neurosci 55:91–98. https://doi.org/10.1007/s12031-014-0345-0
Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710. https://doi.org/10.1126/science.1553558
Rochester CL, Mohsenin V (2002) Respiratory complications of stroke. Semin Respir Crit Care Med 23:248–260. https://doi.org/10.1055/s-2002-33033
Sakamoto F, Hashimoto Y, Kishimoto N, Honda Y, Matsumoto N (2015) The utility of human dedifferentiated fat cells in bone tissue engineering in vitro. Cytotechnology 67:75–84. https://doi.org/10.1007/s10616-013-9659-y
Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM et al (2004) Administration of CD34þ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest 114:330–338. https://doi.org/10.1172/JCI20622
Taguchi A, Wen Z, Myojin K, Yoshihara T, Nakagomi T, Nakayama D, Tanaka H, Soma T, Stern DM, Naritomi H et al (2007) Granulocyte colony-stimulating factor has a negative effect on stroke outcome in a murine model. Eur J Neurosci 26:126–133. https://doi.org/10.1111/j.1460-9568.2007.05640.x
Taguchi A, Kasahara Y, Nakagomi T, Stern DM, Fukunaga M, Ishikawa M, Matsuyama T (2010) A reproducible and simple model of permanent cerebral ischemia in CB-17 and SCID mice. J Exp Stroke Transl Med 3:28–33. https://doi.org/10.6030/1939-067X-3.1.28
Tfilin M, Sudai E, Merenlender A, Gispan I, Yadid G, Turgeman G (2010) Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior. Mol Psychiatry 15:1164–1175. https://doi.org/10.1038/mp.2009.110
Umarova KI, Chugunov AV, Agapov AA, Kamchatnov PR (2007) Pneumonia in patients with acute brain stroke. Zh Nevrol Psikhiatr Im S S Korsakova Suppl 21:25–29
Acknowledgments
The authors thank Assoc. Prof. Takayuki Nakagomi, Akiko Nakakno-Doi from Institute for Advanced Medical Sciences, Hyogo College of Medicine for their valuable comment, and Emeritus Prof. Junichiro Kotani provided helpful comments and suggestions. This work was supported by JSPS KAKENHI Grant Number JP26861759 and JP26463082, and Osaka Dental University Research Funds Number 16-11.
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Kakudo, T., Kishimoto, N., Matsuyama, T. et al. Functional recovery by application of human dedifferentiated fat cells on cerebral infarction mice model. Cytotechnology 70, 949–959 (2018). https://doi.org/10.1007/s10616-018-0193-9
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DOI: https://doi.org/10.1007/s10616-018-0193-9