Axonal regeneration and myelination upon transplantation of genetically modifed adult neural stem cells

• Applicant: Professor Patrick Küry, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277317811

• Final Report Year: 2020

Final Report Abstract

In view of the initially discovered strong inhibitory effect of p57kip2 during oligodendroglial lineage differentiation the overall aim of the project was to test the oligodendrogenic potential of p57kip2-suppressed neural stem cells (NSC) in an adult in vivo CNS environment and to reveal in addition corresponding regenerative reactions within acute CNS lesions. It was found that cutting down p57kip2 in NSCs indeed confers a pro-oligodendroglial effect in the CNS but comes with a limited survival rate probably owing to the fact that oligodendroglia exhibit larger sensitivities in hostile environments. In addition, we identified TIMP-1 as promising MSC secreted factor with the capacity to instruct NSCs in vivo.

Publications

• (2016) Pushing forward: Remyelination as the new frontier in CNS diseases. Trends Neurosci. 39(4):246-63
  Kremer, D., Göttle, P., Hartung, H.P., and Küry, P.
  (See online at https://doi.org/10.1016/j.tins.2016.02.004)
• (2016) Recent achievements in stem cell mediated myelin repair. Curr. Opin. Neurol. 29(3):205–212
  Jadasz; J., Lubetzki, C., Zalc, B., Stankoff, B., Hartung, H.P., and Küry, P.
  (See online at https://doi.org/10.1097/WCO.0000000000000323)
• (2016) Taking Advantage of Nature’s Gift: Can Endogenous Neural Stem Cells Improve Myelin Regeneration? Int. J. Mol. Sci. 17(11). pii: E1895
  Akkermann, R. , Jadasz, J., Azim, K., and Küry, P.
  (See online at https://doi.org/10.3390/ijms17111895)
• (2018) Current advancements in promoting remyelination in multiple sclerosis. Mult. Scler. J 25(1):7-14
  Kremer, D., Akkermann, R., Küry, P., and Dutta, R.
  (See online at https://doi.org/10.1177/1352458518800827)
• (2018) Human mesenchymal factors induce rat hippocampal- and human neural stem cell dependent oligodendrogenesis. Glia 66(1):145-160
  adasz, J., Tepe, L., Beyer, F., Samper-Agrelo, I., Akkermann, R., Spitzhorn, L.S., Silva, M.E., Oreffo, R.O.C., Hartung, H.P., Prigione, A., Rivera, F.J., Adjaye, J., and Küry, P.
  (See online at https://doi.org/10.1002/glia.23233)
• (2018) Rescuing the negative impact of human endogenous retrovirus envelope protein on oligodendroglial differentiation and myelination. Glia 67(1):160-170
  Göttle, P., Förster, M., Gruchot, J., Kremer, D., Hartung, H.P, Perron, H. and Küry, P.
  (See online at https://doi.org/10.1002/glia.23535)
• (2018) Secretome analysis of nerve repair mediating Schwann cells reveals Smad dependent trophism. FASEB J. Apr;33(4):4703- 4715
  Schira, J., Heinen, A., Poschmann, G., Ziegler, B., Hartung, H.P., Stühler, K., and Küry, P.
  (See online at https://doi.org/10.1096/fj.201801799R)
• (2018) Transcriptional profiling of ligand expression in cell specific populations of the adult mouse forebrain that regulates neurogenesis. Frontiers Neurosci. 12:220
  Azim, K., Akkermann, R., Cantone, M., Jadasz, J., Vera, J., and Küry, P.
  (See online at https://doi.org/10.3389/fnins.2018.00220)
• (2019) Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination. Glia 67(8):1510– 1525
  Rivera, F.J., Guzman de la Fuente, A., Zhao, C., Silva, M.E., Gonzalez, G., Wodnar, R., Feichtner, M., Lange, S., Errea, O., Priglinger, E., O´Sullivan, A., Romanelli, P., Jadasz, J.J., Brachtl, G., Greil, R., Tempfer, H., Traweger, A., Bátiz, L.F., Küry, P., Couillard-Despres, S., Franklin, R.J.M., and Aigner, L.
  (See online at https://doi.org/10.1002/glia.23624.)
• (2019) Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models. Int. J. Mol. Sci. 20(2), 455 pii: E455
  Beyer, F., Samper Agrelo, I., and Küry, P.
  (See online at https://doi.org/10.3390/ijms20020455)
• (2019) Remyelination in multiple sclerosis: from concept to clinical trials. Curr. Opin. Neurol. 32:378–384
  Kremer, D., Göttle, P., Flores-Rivera, J., Hartung, H.P., and Küry P.
  (See online at https://doi.org/10.1097/WCO.0000000000000692)
• (2019) Sildenafil inhibits myelin expression and myelination of oligodendroglial precursor cells. ASN Neuro Jan-Dec;11:1759091419832444
  Muñoz-Esquivel, J., Göttle, P., Aguirre-Cruz, L., Flores-Rivera, J., Corona, T., Reyes-Terán, G., Küry, P., Torres, K.J.
  (See online at https://doi.org/10.1177/1759091419832444)
• (2020) Heterogeneous fate choice of genetically modulated adult neural stem cells in grey and white matter of the central nervous system. Glia 68(2):393-406
  Beyer, F., Jadasz, J., Samper Agrelo, I., Schira-Heinen, J., Groh, J., Manousi, A., Bütermann, C., Estrada, V., Reiche, L., Cantone, M., Vera, J., Viganò, F., Dimou, L., Müller, H.W., Hartung, H.P., and Küry, P.
  (See online at https://doi.org/10.1002/glia.23724)
• (2020) Secretome analysis of mesenchymal stem cell factors fostering oligodendroglial differentiation of neural stem cells in vivo. Int. J. Mol. Sci. 21, 4350
  Samper-Agrelo, I., Schira-Heinen, J., Beyer, F., Groh, J., Bütermann, C., Estrada, V., Poschmann, G., Bribian, A., Jadasz, J.J., Lopez-Mascaraque, L., Kremer, D., Martini, R., Müller, H.W., Hartung, H.P., Adjaye, J., Stühler, K., and Küry, P.
  (See online at https://doi.org/10.3390/ijms21124350)