Spontaneously Immortalized Adult Rodent Schwann Cells as Valuable Tools for the Study of Peripheral Nerve Degeneration and Regeneration
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We have established spontaneously immortalized Schwann cell lines from normal adult mice and rats, as well as murine disease models. One of the normal mouse cell lines, IMS32, possesses some biological properties of mature Schwann cells and high proliferative activities. The IMS32 cells have been utilized to investigate the action mechanisms of various molecules involved in peripheral nerve regeneration [e.g., ciliary neurotrophic factor (CNTF), sonic hedgehog, and galectin-1], and the pathogenesis of diabetic neuropathy, particularly the polyol pathway hyperactivity. The cell lines derived from murine disease models (e.g., lysosomal storage diseases, Charcot-Marie-Tooth disease, and neurofibromatosis) retain genomic and biochemical abnormalities, sufficiently representing the pathological features of the mutant mice. A normal rat cell line, IFRS1, retains the characteristic features of mature Schwann cells and the fundamental ability to myelinate axons in coculture with adult rat DRG neurons and PC12 cells. These Schwann cell lines can be valuable tools for exploring neuron–Schwann cell interactions, the pathobiology of axonal degeneration and regeneration in the peripheral nervous system, and novel therapeutic approaches against neurological disorders in patients with relevant diseases.
KeywordsAdult rodents Axonal regeneration Immortalized Schwann cells Murine disease models Myelination Peripheral neuropathies
The work of our laboratory reported in this review was supported by a Grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (grant number: 22500324), the Umehara Fund of the Yokohama Foundation for the Advancement of Medical Science, Japan, and grants from the Sanwa Kagaku Kenkyusho, Suzuken Memorial Foundation, and the Japan Diabetes Foundation. We thank Drs. Koichi Kato, Yasushi Kanazawa, Shizuka Takaku, Hiroko Yanagisawa, and Miwa Sango-Hirade for helpful suggestions; Emiko Kawakami, Kentaro Endo, and the late Kyoko Ajiki for technical assistance with our studies; Enago (www.enago.jp) for the English language review; and John Wiley and Sons for permission to reproduce the illustrations.
- Brannan CI, Perkins AS, Vogel KS, Ratner N, Nordlund ML, Reid SW, Buchberg AM, Jenkins NA, Parada LF, Copeland NG (1994) Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues. Genes Dev 8(9):1019–1029PubMedCrossRefGoogle Scholar
- Calcutt NA, Allendoerfer KL, Mizisin AP, Middlemas A, Freshwater JD, Burgers M, Ranciato R, Delcroix JD, Taylor FR, Shapiro R, Strauch K, Dudek H, Engber TM, Galdes A, Rubin LL, Tomlinson DR (2003) Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy. J Clin Invest 111(4):507–514PubMedCentralPubMedCrossRefGoogle Scholar
- Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, Nagle J, Polymeropoulos MH, Sturley SL, Ioannou YA, Higgins ME, Comly M, Cooney A, Brown A, Kaneski CR, Blanchette-Mackie EJ, Dwyer NK, Neufeld EB, Chang TY, Liscum L, Strauss JF 3rd, Ohno K, Zeigler M, Carmi R, Sokol J, Markie D, O’Neill RR, van Diggelen OP, Elleder M, Patterson MC, Brady RO, Vanier MT, Pentchev PG, Tagle DA (1997) Niemann–Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277(5323):228–231PubMedCrossRefGoogle Scholar
- Eccleston PA, Mirsky R, Jessen KR (1991) Spontaneous immortalisation of Schwann cells in culture: short-term cultured Schwann cells secrete growth inhibitory activity. Development (Camb) 112(1):33–42Google Scholar
- Kawashima I, Watabe K, Tajima Y, Fukushige T, Kanzaki T, Kanekura T, Sugawara K, Ohyanagi N, Suzuki T, Togawa T, Sakuraba H (2007) Establishment of immortalized Schwann cells from Fabry mice and their low uptake of recombinant alpha-galactosidase. J Hum Genet 52(12):1018–1025PubMedCrossRefGoogle Scholar
- Kleitman N, Wood PM, Bunge RP (1998) Tissue culture methods for the study of myelination. In: Banker G, Goslin K (eds) Culturing nerve cells, 2nd edn. MIT Press, Cambridge, pp 545–594Google Scholar
- Ohsawa M, Kotani M, Tajima Y, Tsuji D, Ishibashi Y, Kuroki A, Itoh K, Watabe K, Sango K, Yamanaka S, Sakuraba H (2005) Establishment of immortalized Schwann cells from Sandhoff mice and corrective effect of recombinant human beta-hexosaminidase A on the accumulated GM2 ganglioside. J Hum Genet 50(9):460–467PubMedCrossRefGoogle Scholar
- Sandhoff K (2001) The GM2 gangliosidoses and the elucidation of the β-hexosaminidase system. In: Desnick RJ, Kaback MM (eds) Tay–Sachs disease, vol 44, Advances in genetics. Academic, San Diego, pp 67–91Google Scholar
- Sango K, Yanagisawa H, Watabe K, Horie H, Kadoya T (2012a) Galectin-1 as a multifunctional molecule in the peripheral nervous system after injury. In: Rayegani SM (ed) Basic principles of peripheral nerve disorders. InTech Doo, Rijeka, pp 31–46 http://www.intechopen.com/books/basic-principles-of-peripheral-nerve-disorders/galectin-1-as-a-multifunctional-molecule-in-the-peripheral-nervous-system-after-injury Google Scholar
- Tosaki T, Kamiya H, Yasuda Y, Naruse K, Kato K, Kozakae M, Nakamura N, Shibata T, Hamada Y, Nakashima E, Oiso Y, Nakamura J (2008) Reduced NGF secretion by Schwann cells under the high glucose condition decreases neurite outgrowth of DRG neurons. Exp Neurol 213(2):381–387PubMedCrossRefGoogle Scholar