Axonale Regeneration und Myelinisierung nach Transplantation genetisch modulierter neuraler Stammzellen

• Antragsteller: Professor Patrick Küry, Ph.D.
• Fachliche Zuordnung: Molekulare und zelluläre Neurologie und Neuropathologie
• Förderung: Förderung von 2015 bis 2020
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 277317811

• Erstellungsjahr: 2020

Zusammenfassung der Projektergebnisse

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.

Projektbezogene Publikationen (Auswahl)

• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.
  
• (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.