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Practical application of cell therapy using dedifferentiated fat cells (DFAT) for critical limb ischemia

Practical application of cell therapy using dedifferentiated fat cells (DFAT) for critical limb ischemia

DFAT cells

Scientific papers

  1. Yagi K, Kondo D, Okazaki Y, Kano K. A novel preadipocyte cell line established from mouse adult mature adipocytes. Biochemical and Biophysical Research Communications 321(4):967-974, 2004.
  2. Matsumoto T, Kano K, Kondo D, Iribe Y, Tanaka N, Matsubara Y, Sakuma T, Fukuda N, Satomi A, Otaki M, Ryu J, Mugishima H. Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential. Journal of Cellular Physiology 215(1):210-222, 2008
  3. Ohta Y, Takenaga M, Tokura Y, Hamaguchi A, Matsumoto T, Kano K, Mugishima H, Okano H, Igarashi R. Mature adipocyte-derived cells, DFAT (de-differentiated fat cells) promoted functional recovery from spinal cord injury-induced motor dysfunction in rats. Cell Transplantation 17(8):877-886, 2008
  4. Nur R, Fukuda N, Matsumoto T, Jimabay M, Kano K, Yamamoto C, Maruyama T, Endo M, Matumoto K. Implantation of dedifferentiated fat cells ameliorates Habu Snake Venom-induced chronic renal dysfunction in tenascin-C-deficient mice. Nephron Experimental Nephrology 110(3):e91-98, 2008
  5. Oki Y, Watanabe S, Endo T, Kano K. Mature adipocyte-derived dedifferentiated fat cells can trans-differentiate into osteoblasts in vitro and in vivo only by all-trans retinoic acid. Cell Structure and Function 33(2):211-222, 2008
  6. Kazama T, Fujie M, Endo T, Kano K. Mature adipocyte-derived dedifferentiated fat cells can transdifferentiate into skeletal myocytes in vitro. Biochemical and Biophysical Research Communications 377(3):780-785, 2008
  7. Nobusue H, Endo T, Kano K. Establishment of a preadipocyte cell line derived from mature adipocytes of GFP transgenic mice and formation of adipose tissue. Cell and Tissue Research 332(3):435-446, 2008
  8. Sakuma T, Matsumoto T, Kano K, Fukuda N, Obinata D, Yamaguchi K, Yoshida T, Takahashi S, Mugishima H. Mature adipocyte derived dedifferentiated fat cells can differentiate into smooth muscle-like cells and contribute to bladder tissue regeneration. Journal of Urology 182 (1):355-365, 2009.
  9. Matsubara Y, Kano K, Kondo D, Mugishima H, Matsumoto T. Differences in adipocytokines and fatty acid composition between two adipocyte fractions of smaall and large cells in high-fat diet-induced obese mice. Annals of Nutrition & Metabolism 54(4):258-267, 2009
  10. Matsumura M, Fukuda N, Kobayashi N, Umezawa H, Takasaka A, Matsumoto T, Yao EH, Ueno T, Negishi N. Effects of atrovatatin on angiogenesis in hidlimb ischemia and endothelial progenitor cell formation in rats. Journal of Atherosclerosis and Thrombosis 16(4):319-326, 2009
  11. Jumabay M, Matsumoto T, Yokoyama SI, Kano K, Masuko T, Mitsumata M, Saito S, Hirayama A, Mugishima H, Fukuda N. Dedifferentiated fat cells convert to cardiomyocytes phenotype and repair infarcted cardiac tissue in rats. Journal of Molecular and Cellular Cardiology 47(5):565-575, 2009
  12. Obinata D, Matsumoto T, Ikado Y, Sakuma T, Kano K, Fukuda N, Yamaguchi K, Mugishima H, Takahashi S. Transplantation of mature adipocyte-derived dedifferentiated fat (DFAT) cells improves urethral sphincter contractility in a rat model. International Journal of Urology 18(12):827-834, 2011
  13. Ono H, Oki Y, Bono H, Kano K. Gene expression profiling in multipotent DFAT cells derived from mature adipocytes. Biochemical and Biophysical Research Communications 407(3):562-567, 2011
  14. Kikuta S, Tanaka N, Kazama T, Kazama M, Kano K, Ryu J, Tokuhashi Y, Matsumoto T. Osteogenic effects of dedifferentiated fat (DFAT) cell transplantation in rabbit models of bone defect and ovariectomy (OVX)-induced osteoporosis. Tissue Engineering Part A 19(15-16):1792-1802, 2013
  15. Kono S, Kazama T, Kano K, Harada K, Uechi M, Matsumoto T. Phenotypic and functional properties of feline dedifferentiated fat cells and adipose-derived stem cells. The Veterinary Journal 199(1):88-96, 2014
  16. Matsumine H, Takeuchi Y, Sakaki R, Kazama T, Kano K, Matsumoto T, Sakurai H, Miyata M, Yamato M. Adipocyte-derived and dedifferentiated fat cells promoting facial nerve regeneration in a rat model. Plastic and Reconstructive Surgery 134(4): 686-697, 2014
  17. Mikami Y, Matsumoto T, Kano K, Toriumi T, Somei M, Honda MJ, Komiyama K. Current status of drug therapies for osteoporosis and the search for stem cells adapted for bone regenerative medicine. Anatomical Science International 89(1):1-10, 2014
  18. Yamada H, Ito D, Oki Y, Kitagawa M, Matsumoto T, Watari T, Kano K. Transplantation of mature adipocyte-derived dedifferentiated fat cells promotes locomotor functional recovery by remyelination and glial scar reduction after spinal cord injury in mice. Biochemical and Biophysical Research Communications 454(2):341-346, 2014
  19. Nobusue H, Onishi N, Shimizu T, Sugihara E, Oki Y, Sumikawa Y, CHiyoda T, Akashi K, Saya H, Kano K. Regulation of MLK1 via actin cytoskeleton dynamics drives adipocyte differentiation. Nature Communications 5:3368, 2014
  20. Soejima K, Kashimura T, Asami T, Kazama T, Matsumoto T, Nakazawa H. Effects of mature adipocyte-derived dedifferentiated fat (DFAT) cells on generation and vascularization of dermis like tissue after artificial dermis grafting. Journal of Plastic Surgery and Hand Surgery 49(1): 25-31, 2015
  21. Hsiao AY, Okitsu T, Onoe H, Kiyosawa M, Teramae H, Iwanaga S, Kazama T, Matsumoto T, Takeuchi S. Smooth muscle-like tissue constructs with circumferentially oriented cells formed by the cell fiber technology. PLoS One 10(3):e0119010, 2015
  22. Asami T, Soejima K, Kashimura T, Kazama T, Matsumoto T, Morioka K, Nakazawa H. Effects of combination therapy using basic fibroblast growth factor and mature adipocyte-derived dedifferentiated fat (DFAT) cells on skin graft revascularization. Journal of Plastic Surgery and Hand Surgery 49(4):229-233, 2015
  23. Maruyama T, Fukuda N, Matsumoto T, Kano K, Endo M, Kazama M, Kazama T, Ikeda J, Matsuda H, Ueno T, Abe M, Okada K, Soma M, Matsumoto K, Kawachi H. Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increasing in TNF-stimulated gene 6. Stem Cell Research & Therapy 6(1): 80, 2015
  24. Kashimura T, Soejima K, Asamai T, Kazama T, Matsumoto T, Nakazawa H. The effect of mature adipocyte-derived dedifferentiated fat (DFAT) cells on a dorsal skin flap model. Journal of Investigative Surgery 29(1):6-12, 2016
  25. Nakamura T, Kazama T, Nagaoka Y, Inamo Y, Mugishima H, Takahashi S, Matsumoto T. Influence of donor age and passage number on angiogenic activity in human adipose-derived stem cell-conditioned media. Journal of Stem Cell Research &Therapy 5:307, 2015
  26. Tsurumachi N, Akita D, Kano K, Matsumoto T, Toriumi T, kazama T, Oki Y, Tamura Y, Tonogi M, Isokawa K, Shimizu N, Honda M. Small buccal fat pad cells have high osteogenic differentiation potential. Tissue Engineering Part C 22(3): 250-259, 2016
  27. Taniguchi H, Kazama T, Hagikura K, Yamamoto C, Kazama M, Nagaoka Y, Matsumoto T. An efficient method to obtain dedifferentiated fat cells. Journal of Visualized Experiments Jul 15;(113), e54177, 2016.
  28. Akita D, Kano K, Saito-Tamura Y, Mashimo T, Sato-Shionome M, Tsurumachi N, Yamanaka K, Kaneko T, Toriumi T, Arai Y, Tsukimura N, Matsumoto T, Ishigami T, Isokawa K, Honda M. Use of rat mature adipocyte-derived dedifferentiated fat cells as a cell source for periodontal tissue regeneration. Frontiers in Physiology 7: 50, 2016
  29. Ikado Y, Obinata D, Matsumoto T, Murata Y, Kano K, Fukuda N, Yamaguchi K, Takahashi S. Transplantation of mature adipocyte-derived dedifferentiated fat cells for treatment of vesicoureteral reflux in a rat model. International Urology and Nephrology 48(12): 1951-1960, 2016.
  30. Murai T, Matsumoto T, Ishige M, Kazama T, Kano K, Mugishima H. Effect of dedifferentiated fat cell transplantation in a mouse model of acute graft-versus-host disease. J Nihon Univ Med 76(4-5): 187-194, 2017
  31. Toyama K, Kano K, Matsumoto T, Hirayama A. Study of cardiac muscle differentiation potential in epicardial adipose-derived dedifferentiated fat cells (DFAT). J Nihon Univ Med 76(4-5): 175-185, 2017
  32. Suzuki D, Akita D, Tsurumachi N, Kano K, Yamanaka K, Kaneko T, Kawano E, Iguchi S, Toriumi T, Arai Y, Matsumoto T, Isokawa K, Sato S, Honda M. Transplantation of mature adipocyte-derived dedifferentiated fat cells into three-wall defects in the rat periodontium induces tissue regeneration. Journal of Oral Science 59(4):611-620, 2017
  33. Mikrogeorgiou A, Kondo T, Hattori T, Sugiyama Y, Nakanishi K, Tsuji M, Kazama T, Kano K, Matsumoto T, Hayakawa M, Sato Y. Dedifferentiated fat cells, as a novel source for cell therapy to target neonatal hypoxic ischemic encephalopathy. Developmental Neuroscience 39(1-4):273-286, 2017
  34. Nakayama E, Matsumoto T, Kazama T, Kano K, Tokuhashi Y. Transplantation of dedifferentiated fat cells promotes intervertebral disc regeneration in a rat intervertebral disc degeneration model. Biochemical and Biophysical Research Communications 493(2):1004-1009, 2017.
  35. Tsurumachi N, Akita D, Kano K, Matsumoto T, Toriumi T, Kazama T, Oki Y, Saito-Tarura Y, Tonogi M, Shimizu N, Honda M. Effect of collagenase concentration on the isolation of small adipocytes from human buccal fat pad. Journal of Oral Science 60(1):14-23, 2018
  36. Shimizu M, Matsumoto T, Kikuta S, Ohtaki M, Kano K, Taniguchi H, Saito S, Nagaoka M, Tokuhashi Y. Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model. Journal of Orthopaedic Science 23(4):688-696, 2018
  37. Soejima K, Kashimura T, Kazama T, Matsumoto T, Nakazawa H. Effect of mature adipocyte-derived fat (DFAT) cells on formation of basement membrane after cultured epithelial autograft on artificial dermis. Plastic and Reconstructive Surgery 143(5):983e-992e, 2019
  38. Sakuma T, Matsumoto T, Kazama T, Tokuhashi Y. Analysis of cell-to-cell interactions between intervertebral nucleus pulposus cells and dedifferentiated fat cells using a coculture system. J Nihon Univ Med 78(4-5): 285-293, 2019
  39. Fujimaki H, Matsumine H, Osaki H, Ueta Y, Kamei W, Shimizu M, Hashiomto K, Fujii K, Kazama T, Matsumoto T, Niimi Y, Miyaka M, Sakurai H. Dedifferentiated fat cells in polyglycolic acid-collagen nerve conduits promote rat facial nerve regeneration. Regenerative Therapy 11:240-248, 2019
  40. Yamazaki T, Kishimoto T, Leszcznski P, Sadakane K, Kenmotsu T, Watanabe H, Kazama T, Matsumoto T, Yoshikawa K, Taniguchi H. Construction of 3D cellular composites with stem cells derived from adipose tissue and endothelial cells by use of optical tweezers in a natural polymer solution. Materials. 2019, 12(11) pii: E1759, doi:10.3390/ma12111759
  41. Nakano R, Kitanaka T, Namba S, Kitanaka N, Sato M, Shibukawa Y, Masuhiro Y, Kano K, Matsumoto T, Sugiya H. All-trans retinoic acid induces reprogrammig of canine dedifferentiated cells into neuron-like cells. PLoS One. 2020, 15(3):e0229892, doi:10.1371/journal.pone.0229892.
  42. Watanabe H, Goto S, Kato R, Komiyama S, Nagaoka Y, Kazama T, Yamamoto C, Li Y, Konuma N, Hagikura K, Matsumoto T. The neovascularization effect of dedifferentiated fat cells. Scientific Reports 10(1):9211, 2020
  43. Ishioka S, Hosokawa T, Ikeda T, Konuma N, Kaneda H, Ohashi K, Furuya T, Masuko T, Taniguchi H, Kano K, Koshinaga T, Matsumoto T. Therapeutic potential of mature adipocyte-derived dedifferentiated fat cells for inflammatory bowel disease. Pediatric Surgery International 36(7):799-807, 2020
  44. Kawachi H, Matsumoto T, Kazama T, Yamamoto C, Kano K, Maeda H, Kono K, Shiono M. Tanaka M. The effect of autologous dedifferentiated fat cell transplantation in a pig model of hindlimb ischemia. Journal of Nihon University School of Medicine 79(3): 133-143, 2020
  45. Yamada T, Matsumoto T, Kazama T, Arai Y, Kano K, Tokuhashi Y, Nakanishi K. Promoting effect of dedifferentiated fat cell transplantation on bone formation in a mouse femoral fracture model. Journal of Nihon University School of Medicine 79(5):265-273, 2020
  46. Hashimoto M, Uekusa S, Ono K, Goto S, Hosokawa T, Koshinaga T, Matsumoto T. Establishment of induced pluripotent stem cells from dedifferentiated adipocytes. Journal of Nihon University School of Medicine 79(5):275-286, 2020
  47. Tanimoto K, Matsumoto T, Nagaoka Y, Kazama T, Yamamoto C, Kano K, Nagaoka M, Saito S, Tokuhashi Y, Nakanishi K. Phenotypic and functional properties of dedifferentiated fat cells derived from infrapatellar fat pad. Regenerative Therapy 19:35-46, 2022
  48. Akita D, Kazama T, Tsukimura N, Taniguchi Y, Takahashi R, Arai Y, Tsurumachi-Iwasaki N, Yasuda H, Okubo T, Kano K, Matsumoto T, Honda M. Transplantation of mature adipocyte-derived dedifferentiated fat cells facilitates periodontal tissue regeneration of class II furcation defects in miniature pigs. Materials 15(4):1311, 2022
  49. Murata Y, Obinata D, Matsumoto T, Ikado Y, Kano K, Fukuda N, Yamaguchi K, Takahashi S. Urethral injection of dedifferentiated fat cells ameliorates sphincter damage and voiding dysfunction in a rat model of persistence stress urinary incontinence. International Urology and Nephrology 54(4):789-797, 2022
  50. Utsunomiya K, Maruyama T, Shimizu S, Matsumoto T, Endo M, Kobayashi H, Kano K, Abe M, Fukuda N. Implantation of dedifferentiated fat cells ameliorated antineutrophil cytoplasmic antibody glomerulonephritis by immunosuppression and increases in tumor necrosis factor-stimulated gene-6. Stem Cell Research & Therapy 13(1): 319, 2022
  51. Hidaka A, Uekusa S, Hosokawa T, Kaneda H, Kazama T, Hagikura K, Uehara S, Koshinaga T, Matsumoto T. Effects of dedifferentiated fat cells on neurogenic differentiation and cell proliferation in neuroblastoma cells. Pediatric Surgery International 39(1): 58, 2022
  52. Sawada H, Kazama T, Nagaoka Y, Arai Y, Kano K, Uei H, Tokuhashi Y, Nakanishi K, Matsumoto T. Bone marrow-derived dedifferentiated fat cells exhibit similar phenotype as bone marrow mesenchymal stem cells with high osteogenic differentiation and bone regeneration ability. Journal of Orthopaedic Surgery and Research 18(1):191, 2023
  53. Mimatsu H, Onoda A, Kazama T, Nishijima K, Shinoyama Y, Go S, Ueda K, Takahashi Y, Matsumoto T, Hayakawa M, Sato Y. Dedifferentiated fat cells administration ameliorates abnormal expression of fatty acids metabolism-related protein expressions and intestinal tissue damage in experimental necrotizing enterocolitis. Scientific Reports 13(1):8266, 2023