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Defective Self-Renewal and Differentiation of GBA-Deficient Neural Stem Cells Can Be Restored By Macrophage Colony-Stimulating Factor

  • 투고 : 2015.05.04
  • 심사 : 2015.06.18
  • 발행 : 2015.09.30

초록

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (GBA), which encodes the lysosomal enzyme glucosylceramidase (GCase). Deficiency in GCase leads to characteristic visceral pathology and lethal neurological manifestations in some patients. Investigations into neurogenesis have suggested that neurodegenerative disorders, such as GD, could be overcome or at least ameliorated by the generation of new neurons. Bone marrowderived mesenchymal stem cells (BM-MSCs) are potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. Our objective was to examine the mechanism of neurogenesis by BM-MSCs in GD. We found that neural stem cells (NSCs) derived from a neuronopathic GD model exhibited decreased ability for self-renewal and neuronal differentiation. Co-culture of GBA-deficient NSCs with BM-MSCs resulted in an enhanced capacity for self-renewal, and an increased ability for differentiation into neurons or oligodendrocytes. Enhanced proliferation and neuronal differentiation of GBA-deficient NSCs was associated with elevated release of macrophage colony-stimulating factor (M-CSF) from BM-MSCs. Our findings suggest that soluble M-CSF derived from BM-MSCs can modulate GBA-deficient NSCs, resulting in their improved proliferation and neuronal differentiation.

과제정보

연구 과제 주관 기관 : Korea Health Industry Development Institute (KHIDI)

참고문헌

  1. Adachi, M., Wallace, B.J., Schneck, L., and Volk, B.W. (1967). Fine structure of central nervous system in early infantile Gaucher's disease. Arch. Pathol. 83, 513-526.
  2. Bae, J.S., Han, H.S., Youn, D.H., Carter, J.E., Modo. M., Schuchman, E.H., and Jin, H.K. (2007). Bone marrow-derived mesenchymal stem cells promote neuronal networks with functional synaptic transmission after transplantation into mice with neurodegeneration. Stem Cells 25, 1307-1316. https://doi.org/10.1634/stemcells.2006-0561
  3. Bajetto, A., Bonavia, R., Barbero, S., Florio, T., and Schettini, G. (2001). Chemokines and their receptors in the central nervous system. Front Neuroendocrinol. 22, 147-184. https://doi.org/10.1006/frne.2001.0214
  4. Beutler, E., and Grabowski, G.A. (2001). Glucosylceramide lipidosis-Gaucher disease. In: C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle, eds. The metabolic and molecular bases of inherited diseases. 8th ed. (New York, USA: McGraw-Hill), pp. 3635-3668.
  5. Block, G.J., Ohkouchi, S., Fung, F., Frenkel, J., Gregory, C., Pochampally, R., DiMattia, G., Sullivan, D.E., and Prockop, D.J. (2009). Multipotent stromal cells are activated to reduce apoptosis in part by upregulation and secretion of stanniocalcin-1. Stem Cells 27, 670-681. https://doi.org/10.1002/stem.20080742
  6. Brady, R.O., Kanfer, J.N., Bradley, R.M., and Shapiro, D. (1966). Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher's disease. J. Clin. Invest. 45, 1112-1115. https://doi.org/10.1172/JCI105417
  7. Chen, Y., Balasubramaniyan, V., Peng, J., Hurlock, E.C., Tallquist, M., Li, J., and Lu, Q.R. (2007). Isolation and culture of rat and mouse oligodendrocyte precursor cells. Nat. Protoc. 2, 1044-1051. https://doi.org/10.1038/nprot.2007.149
  8. Conradi, N.G., Sourander, P., Nilsson, O., Svennerholm, L., and Erikson, A. (1984). Neuropathology of the Norrbottnian type of Gaucher disease. Morphological and biochemical studies. Acta Neuropathol. 65, 99-109. https://doi.org/10.1007/BF00690463
  9. Conradi, N.G., Kalimo, H., and Sourander, P. (1988). Reactions of vessel walls and brain parenchyma to the accumulation of Gaucher cells in the Norrbottnian type (type III) of Gaucher disease. Acta Neuropathol. 75, 385-390. https://doi.org/10.1007/BF00687792
  10. Croft, A.P., and Przyborski, S.A. (2009). Mesenchymal stem cells expressing neural antigens instruct a neurogenic cell fate on neural stem cells. Exp. Neurol. 216, 329-341. https://doi.org/10.1016/j.expneurol.2008.12.010
  11. Deng, Y.B., Liu, X.G., Liu, Z.G., Liu, X.L., Liu, Y., and Zhou, G.Q. (2006). Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery: evidence from a study in rhesus monkeys. Cytotherapy 8, 210-214. https://doi.org/10.1080/14653240600760808
  12. Enquist, I.B., Lo Bianco, C., Ooka, A., Nilsson, E., Mansson, J.E., Ehinger, M., Richter, J., Brady, R.O., Kirik, D., Karlsson, S. (2007). Murine models of acute neuronopathic Gaucher disease. Proc. Natl. Acad. Sci. USA 104, 17483-17488. https://doi.org/10.1073/pnas.0708086104
  13. Farfel-Becker, T., Vitner, E., Dekel, H., Leshem, N., Enquist, I.B., Karlsson, S., and Futerman, A.H. (2009). No evidence for activation of the unfolded protein response in neuronopathic models of Gaucher disease. Hum. Mol. Genet. 18, 1482-1488. https://doi.org/10.1093/hmg/ddp061
  14. Farfel-Becker, T., Vitner, E.B., Pressey, S.N., Eilam, R., Cooper, J.D., Futerman, A.H. (2011). Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease. Hum. Mol..Genet. 20, 1375-1386. https://doi.org/10.1093/hmg/ddr019
  15. He, X., Dagan, A., Gatt, S., and Schuchman, E.H. (2005). Simultaneous quantitative analysis of ceramide and sphingosine in mouse blood by naphthalene-2,3-dicarboxyaldehyde derivatization after hydrolysis with ceramidase. Anal. Biochem. 340, 113-122. https://doi.org/10.1016/j.ab.2005.01.058
  16. He, X., Huang, Y., Li, B., Gong, C.X., and Schuchman, E.H. (2010). Deregulation of sphingolipid metabolism in Alzheimer's disease. Neurobiol. Aging 31, 398-408. https://doi.org/10.1016/j.neurobiolaging.2008.05.010
  17. Kaga, M., Azuma, C., Imamura, T., Murakami, T., and Kaga, K. (1982). Auditory brainstem response (ABR) in infantile Gaucher's disease. Neuropediatrics 13, 207-210. https://doi.org/10.1055/s-2008-1059624
  18. Kaga, K., Ono, M., Yakumaru, K., Owada, M., and Mizutani, T. (1998). Brainstem pathology of infantile Gaucher's disease with only wave I and II of auditory brainstem response. J. Laryngol. Otol. 112, 1069-1073.
  19. Lee, H., Kang, J.E., Lee, J.K., Bae, J.S., and Jin, H.K. (2013). Bone-marrow-derived mesenchymal stem cells promote proliferation and neuronal differentiation of Niemann-Pick type C mouse neural stem cells by upregulation and secretion of CCL2. Hum. Gene. Ther. 24, 655-669. https://doi.org/10.1089/hum.2013.001
  20. Ming, G.L., and Song, H. (2011). Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70, 687-702. https://doi.org/10.1016/j.neuron.2011.05.001
  21. Motabar, O., Goldin, E., Leister, W., Liu, K., Southall, N., Huang, W., Marugan, J.J., Sidransky, E., and Zheng, W. (2012). A high throughput glucocerebrosidase assay using the natural substrate glucosylceramide. Anal. Bioanal. Chem. 402, 731-739. https://doi.org/10.1007/s00216-011-5496-z
  22. Nandi, S., Gokhan, S., Dai, X.M., Wei, S., Enikolopov, G., Lin, H., Mehler, M.F., and Stanley, E.R. (2012). The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation. Dev. Biol. 367, 100-113. https://doi.org/10.1016/j.ydbio.2012.03.026
  23. Parr, A.M., Tator, C.H., and Keating, A. (2007). Bone marrow derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant. 40, 609-619. https://doi.org/10.1038/sj.bmt.1705757
  24. Prockop, D.J. (2007). "Stemness" does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin. Pharmacol. Ther. 82, 241-243. https://doi.org/10.1038/sj.clpt.6100313
  25. Prockop, D.J., Gregory, C.A., and Spees, J.L. (2003). One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc. Natl. Acad. Sci. USA 100, 11917-11923. https://doi.org/10.1073/pnas.1834138100
  26. Ren, G., Li, T., Lan, J.Q., Wilz, A., Simon, R.P., and Boison, D. (2007). Lentiviral RNAi-induced downregulation of adenosine kinase in human mesenchymal stem cell grafts: a novel perspective for seizure control. Exp. Neurol. 208, 26-37. https://doi.org/10.1016/j.expneurol.2007.07.016
  27. Reynolds, B.A., and Weiss, S. (1996). Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev. Biol. 175, 1-13. https://doi.org/10.1006/dbio.1996.0090
  28. Sidransky, E. (2004). Gaucher disease: complexity in a 'simple' disorder. Mol. Genet. Metab. 83, 6-15. https://doi.org/10.1016/j.ymgme.2004.08.015
  29. Tayebi, N., Reissner, K.J., Lau, E.K., Stubblefield, B.K., Klineburgess, A.C., Martin, B.M., and Sidransky, E. (1998). Genotypic heterogeneity and phenotypic variation among patients with type 2 Gaucher's disease. Pediatr. Res. 43, 571-578. https://doi.org/10.1203/00006450-199805000-00003
  30. Tylki-Szymanska, A., Vellodi, A., El-Beshlawy, A., Cole, J.A., and Kolodny, E. (2010). Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry. J. Inherit. Metab. Dis. 33, 339-346. https://doi.org/10.1007/s10545-009-9009-6
  31. Yoo, S.W., Kim, S.S., Lee, S.Y., Lee, H.S., Kim, H.S., Lee, Y.D., Suh-Kim, H. (2008). Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model. Exp. Mol. Med. 40, 387-397. https://doi.org/10.3858/emm.2008.40.4.387
  32. Zhang, J., Li, Y., Chen, J., Yang, M., Katakowski, M., Lu, M., and Chopp, M. (2004). Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells. Brain Res. 1030, 19-27. https://doi.org/10.1016/j.brainres.2004.09.061
  33. Zhang, J., Li, Y., Chen, J., Cui, Y., Lu, M., Elias, S.B., Mitchell, J.B., Hammill, L., Vanguri, P., and Chopp, M. (2005). Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp. Neurol. 195, 16-26. https://doi.org/10.1016/j.expneurol.2005.03.018

피인용 문헌

  1. Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System vol.39, pp.6, 2016, https://doi.org/10.1016/j.tins.2016.03.005
  2. Delineating pathological pathways in a chemically induced mouse model of Gaucher disease vol.239, pp.4, 2016, https://doi.org/10.1002/path.4751