Researchers at the University of Florida, USA, led by Dr. K. Wang have demonstrated that inhibition of Rho-associated kinase (ROCK) and subsequent cofilin dephosphorylation is mediating neurite outgrowth in PC12 cells. The lack of axonal regeneration in adult central nervous system (CNS) is one of the main cause of neurodegenerative disorders. Thus ROCK inhibition mediated neurite outgrowth is clinically relevant to treat CNS diseases such as Alzheimer's disease, spinal cord injury, traumatic brain injury and stroke (Zhang et al., 2006).
In a follow up study by Prof. W.S. Poon and Dr. P.K. Lam's team from The Chinese University of Hong Kong and Dr. Wang's group, they successfully transplanted mesenchymal stem cells (MSCs) to the brain by topical application in an experimental traumatic brain injury model. Indeed, MSCs delivered to the brain surface were able to migrate to the damaged TBI site. This novel approach makes up for the numerous drawbacks associated with systemic infusion. Moreover, MSCs are capable of neurorepair and neuroprotection, which make their successful transplantation even more significant (Lam et al., 2013).
A combination of these different results can be therapeutically valuable to treat neurodegenerative disorders. As illustrated in this mini-review published in Neural Regeneration Research, Vol. 9, No.: "other and our laboratories are increasingly focusing on combining the use of pharmacological agents (such as Rho-associated kinase (ROCK) inhibitors or other growth factors (such as BDNF) and stem cell treatment to enhance the survivability and/or differentiation capacity of transplanted stem cells in neurotrauma or other neurodegeneration animal models". Nonetheless, the author highlighted the fact that "we still haven't fully grasped the concept of neurogenesis and how it really works", although it is primordial if we want to conceive new therapeutic techniques for neurodegenerative diseases and injuries.
Lam, P.K., et al., 2013. Transplantation of mesenchymal stem cells to the brain by topical application in an experimental traumatic brain injury model. J Clin Neurosci. 20, 306-9. Zhang, Z., et al., 2006. Direct Rho-associated kinase inhibition [correction of inhibiton] induces cofilin dephosphorylation and neurite outgrowth in PC-12 cells. Cell Mol Biol Lett. 11, 12-29.
Article: "Stem cells in neurodegeneration: challenges and future neurotherapeutic prospects" by Tarek H. Mouhieddine1, Firas H. Kobeissy1, 2, Muhieddine Itani3, Amaly Nokkari4, Kevin K.W. Wang2
(1 Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 2 Center for Neuroproteomics and Biomarkers Research, Department of Psychiatry, Gainesville, Division of Addiction Medicine, Department of Psychiatry, University of Florida, Gainesville, FL 32610, USA; 3 Faculty of Medicine, Saint George University of London, Nicosia, Cyprus; 4 Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon)
Mouhieddine TH, Kobeissy FH, Itani M, Nokkari A, Wang KKW. Stem cells in neuroinjury and neurodegenerative disorders: challenges and future neurotherapeutic prospects. Neural Regen Res. 2014;9(9): 901-906.
Neural Regeneration Research