Central Nervous System; Ion Channels; Nerve Regeneration; Neurology; Neurosciences; Spinal Cord; Spinal Cord Injuries; Veterans; Cell Transplantation
Stem Cell Center, Yale: Stem Cells and Tissue Repair | Tissue Specific Stem Cells
My research program focuses on cell transplantation strategies to repair the damaged spinal cord. We have shown that a number of cell types can both remyelinate the demyelinated CNS and encourage CNS axonal regeneration. Our laboratory utilizes a number of cellular and electrophysiological techniques to study cell transplant-induced repair.
While most of our work utilizes rodent models, we also use nonhuman primates. Although direct surgical implantation of cells is a reasonable approach for cell delivery in single lesion sites, multiple sclerosis is complicated by numerous demyelinated sites within the CNS. We have shown that intravenous delivery of a bone marrow cell fraction enriched with mesenchymal stem cells (MSCs) can home to a demyelinated lesion in the rodent spinal cord and remyelinate the damaged axons.
This suggests the intriguing prospect that methods could be developed for autologous intravenous delivery of cells that could repair demyelinated lesions scattered throughout the CNS. We are aggressively studying this approach in various demyelinating lesion models.
Specialized Terms: Transplantation-based approaches toward restoration; Preservation of function in the injured central nervous system; Axonal regeneration; Cell transplantation; Ion channels; Nerve injury; Remyelination; Spinal cord injury
Demyelinating diseases and potential repair strategies.
Radtke, C., Spies, M., Sasaki, M., Vogt, P.M., and Kocsis, J.D. (2007). Demyelinating diseases and potential repair strategies. Int. J. Dev. Neurosci. 3:149-153.
Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells.
Dombrowski, M.A., Sasaki, M., Lankford, K.L., Kocsis, J.D., and Radtke C. (2007). Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells. Brain Res. 1125(1):1-8.
Full List of PubMed Publications
- Nakazaki M, Sasaki M, Kataoka-Sasaki Y, Oka S, Namioka T, Namioka A, Onodera R, Suzuki J, Sasaki Y, Nagahama H, Mikami T, Wanibuchi M, Kocsis JD, Honmou O: Intravenous infusion of mesenchymal stem cells inhibits intracranial hemorrhage after recombinant tissue plasminogen activator therapy for transient middle cerebral artery occlusion in rats. J Neurosurg. 2017 Oct; 2017 Jan 6. PMID: 28059661
- Lankford KL, Arroyo EJ, Kocsis JD: Chronic TNFα Exposure Induces Robust Proliferation of Olfactory Ensheathing Cells, but not Schwann Cells. Neurochem Res. 2017 Sep; 2017 May 11. PMID: 28497341
- Noshiro S, Mikami T, Kataoka-Sasaki Y, Sasaki M, Hashi K, Ohtaki S, Wanibuchi M, Mikuni N, Kocsis JD, Honmou O: Biological relevance of tissue factor and IL-6 in arteriovenous malformations. Neurosurg Rev. 2017 Jul; 2016 Aug 19. PMID: 27542852
- Noshiro S, Mikami T, Kataoka-Sasaki Y, Sasaki M, Ohnishi H, Ohtaki S, Wanibuchi M, Mikuni N, Kocsis JD, Honmou O: Co-expression of tissue factor and IL-6 in immature endothelial cells of cerebral cavernous malformations. J Clin Neurosci. 2017 Mar; 2017 Jan 10. PMID: 28087183
- Torii M, Sasaki M, Chang YW, Ishii S, Waxman SG, Kocsis JD, Rakic P, Hashimoto-Torii K: Detection of vulnerable neurons damaged by environmental insults in utero. Proc Natl Acad Sci U S A. 2017 Feb 28; 2017 Jan 25. PMID: 28123061
- Nakamura H, Sasaki Y, Sasaki M, Kataoka-Sasaki Y, Oka S, Nakazaki M, Namioka T, Namioka A, Onodera R, Suzuki J, Nagahama H, Mikami T, Wanibuchi M, Kocsis JD, Honmou O: Elevated brain derived neurotrophic factor (BDNF) levels in plasma but not serum reflect in vivo functional viability of infused mesenchymal stem cells after middle cerebral artery occlusion in rat. J Neurosurg Sci. 2017 Feb 8; 2017 Feb 8. PMID: 28181779
- Ohtaki S, Wanibuchi M, Kataoka-Sasaki Y, Sasaki M, Oka S, Noshiro S, Akiyama Y, Mikami T, Mikuni N, Kocsis JD, Honmou O: ACTC1 as an invasion and prognosis marker in glioma. J Neurosurg. 2017 Feb; 2016 Apr 15. PMID: 27081897
- Sasaki Y, Sasaki M, Kataoka-Sasaki Y, Nakazaki M, Nagahama H, Suzuki J, Tateyama D, Oka S, Namioka T, Namioka A, Onodera R, Mikami T, Wanibuchi M, Kakizawa M, Ishiai S, Kocsis JD, Honmou O: Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats. Phys Ther. 2016 Nov; 2016 May 12. PMID: 27174259
- Morita T, Sasaki M, Kataoka-Sasaki Y, Nakazaki M, Nagahama H, Oka S, Oshigiri T, Takebayashi T, Yamashita T, Kocsis JD, Honmou O: Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury. Neuroscience. 2016 Oct 29; 2016 Aug 30. PMID: 27586052
- Takayanagi A, Sasaki M, Kataoka-Sasaki Y, Kobayashi K, Matsuda Y, Oka S, Masumori N, Kocsis JD, Honmou O: Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat Model of Cavernous Nerve Injury. J Sex Med. 2015 Aug; 2015 Jul 24. PMID: 26211660
- Matsushita T, Lankford KL, Arroyo EJ, Sasaki M, Neyazi M, Radtke C, Kocsis JD: Diffuse and persistent blood-spinal cord barrier disruption after contusive spinal cord injury rapidly recovers following intravenous infusion of bone marrow mesenchymal stem cells. Exp Neurol. 2015 May; 2015 Mar 12. PMID: 25771801
- Lerner MZ, Matsushita T, Lankford KL, Radtke C, Kocsis JD, Young NO: Intravenous mesenchymal stem cell therapy after recurrent laryngeal nerve injury: a preliminary study. Laryngoscope. 2014 Nov; 2014 Jul 7. PMID: 25043703
- Lankford KL, Brown RJ, Sasaki M, Kocsis JD: Olfactory ensheathing cells, but not Schwann cells, proliferate and migrate extensively within moderately X-irradiated juvenile rat brain. Glia. 2014 Jan; 2013 Oct 24. PMID: 24166823
- Matthes SM, Reimers K, Janssen I, Liebsch C, Kocsis JD, Vogt PM, Radtke C: Intravenous transplantation of mesenchymal stromal cells to enhance peripheral nerve regeneration. Biomed Res Int. 2013; 2013 Dec 26. PMID: 24459671
- Kocsis JD, Honmou O: Bone marrow stem cells in experimental stroke. Prog Brain Res. 2012. PMID: 23186711
- Sasaki M, Lankford KL, Radtke C, Honmou O, Kocsis JD: Remyelination after olfactory ensheathing cell transplantation into diverse demyelinating environments. Exp Neurol. 2011 May; 2011 Jan 28. PMID: 21281634
- Radtke C, Sasaki M, Lankford KL, Gallo V, Kocsis JD: CNPase expression in olfactory ensheathing cells. J Biomed Biotechnol. 2011; 2011 Nov 16. PMID: 22174557
- Sasaki M, Honmou O, Radtke C, Kocsis JD: Development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of i.v. infusion of human mesenchymal stem cells. PLoS One. 2011; 2011 Oct 24. PMID: 22039510
- Sasaki M, Lankford KL, Brown RJ, Ruddle NH, Kocsis JD: Focal experimental autoimmune encephalomyelitis in the Lewis rat induced by immunization with myelin oligodendrocyte glycoprotein and intraspinal injection of vascular endothelial growth factor. Glia. 2010 Oct. PMID: 20645414
- Radtke C, Vogt PM, Devor M, Kocsis JD: Keratinocytes acting on injured afferents induce extreme neuronal hyperexcitability and chronic pain. Pain. 2010 Jan; 2009 Nov 22. PMID: 19932564
- Radtke C, Lankford KL, Wewetzer K, Imaizumi T, Fodor WL, Kocsis JD: Impaired spinal cord remyelination by long-term cultured adult porcine olfactory ensheathing cells correlates with altered in vitro phenotypic properties. Xenotransplantation. 2010 Jan-Feb. PMID: 20149190
- Sasaki M, Radtke C, Tan AM, Zhao P, Hamada H, Houkin K, Honmou O, Kocsis JD: BDNF-hypersecreting human mesenchymal stem cells promote functional recovery, axonal sprouting, and protection of corticospinal neurons after spinal cord injury. J Neurosci. 2009 Nov 25. PMID: 19940189
- Markakis EA, Sasaki M, Lankford KL, Kocsis JD: Convergence of cells from the progenitor fraction of adult olfactory bulb tissue to remyelinating glia in demyelinating spinal cord lesions. PLoS One. 2009 Sep 29; 2009 Sep 29. PMID: 19787061
- Kocsis JD, Lankford KL, Sasaki M, Radtke C: Unique in vivo properties of olfactory ensheathing cells that may contribute to neural repair and protection following spinal cord injury. Neurosci Lett. 2009 Jun 12; 2009 Jan 17. PMID: 19429149
- Radtke C, Aizer AA, Agulian SK, Lankford KL, Vogt PM, Kocsis JD: Transplantation of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair. Brain Res. 2009 Feb 13; 2008 Nov 21. PMID: 19059220
- Kocsis JD, Tessler A: Pathology of blast-related brain injury. J Rehabil Res Dev. 2009. PMID: 20104396
- Sasaki M, Honmou O, Kocsis JD: A rat middle cerebral artery occlusion model and intravenous cellular delivery. Methods Mol Biol. 2009. PMID: 19378204
- Lankford KL, Sasaki M, Radtke C, Kocsis JD: Olfactory ensheathing cells exhibit unique migratory, phagocytic, and myelinating properties in the X-irradiated spinal cord not shared by Schwann cells. Glia. 2008 Nov 15. PMID: 18551623
- Kocsis JD, Waxman SG: Schwann cells and their precursors for repair of central nervous system myelin. Brain. 2007 Aug; 2007 Jul 11. PMID: 17626033
- Sasaki M, Li B, Lankford KL, Radtke C, Kocsis JD: Remyelination of the injured spinal cord. Prog Brain Res. 2007. PMID: 17618995
- Dombrowski MA, Sasaki M, Lankford KL, Kocsis JD, Radtke C: Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells. Brain Res. 2006 Dec 13; 2006 Nov 16. PMID: 17112480
- Sasaki M, Hains BC, Lankford KL, Waxman SG, Kocsis JD: Protection of corticospinal tract neurons after dorsal spinal cord transection and engraftment of olfactory ensheathing cells. Glia. 2006 Mar. PMID: 16288464
- Sasaki M, Black JA, Lankford KL, Tokuno HA, Waxman SG, Kocsis JD: Molecular reconstruction of nodes of Ranvier after remyelination by transplanted olfactory ensheathing cells in the demyelinated spinal cord. J Neurosci. 2006 Feb 8. PMID: 16467529
- Radtke C, Akiyama Y, Lankford KL, Vogt PM, Krause DS, Kocsis JD: Integration of engrafted Schwann cells into injured peripheral nerve: axonal association and nodal formation on regenerated axons. Neurosci Lett. 2005 Oct 21. PMID: 16084645
- Yu K, Kocsis JD: Schwann cell engraftment into injured peripheral nerve prevents changes in action potential properties. J Neurophysiol. 2005 Aug. PMID: 16061494
- Sasaki M, Lankford KL, Zemedkun M, Kocsis JD: Identified olfactory ensheathing cells transplanted into the transected dorsal funiculus bridge the lesion and form myelin. J Neurosci. 2004 Sep 29. PMID: 15456822
- Kocsis JD, Akiyama Y, Radtke C: Neural precursors as a cell source to repair the demyelinated spinal cord. J Neurotrauma. 2004 Apr. PMID: 15115593
- Radtke C, Akiyama Y, Brokaw J, Lankford KL, Wewetzer K, Fodor WL, Kocsis JD: Remyelination of the nonhuman primate spinal cord by transplantation of H-transferase transgenic adult pig olfactory ensheathing cells. FASEB J. 2004 Feb; 2003 Dec 4. PMID: 14657003
- Akiyama Y, Lankford K, Radtke C, Greer CA, Kocsis JD: Remyelination of spinal cord axons by olfactory ensheathing cells and Schwann cells derived from a transgenic rat expressing alkaline phosphatase marker gene. Neuron Glia Biol. 2004 Feb. PMID: 16799702
- Tokuno HA, Bradberry CW, Everill B, Agulian SK, Wilkes S, Baldwin RM, Tamagnan GD, Kocsis JD: Local anesthetic effects of cocaethylene and isopropylcocaine on rat peripheral nerves. Brain Res. 2004 Jan 23. PMID: 14697493
- White FA, Kocsis JD: A-fiber sprouting in spinal cord dorsal horn is attenuated by proximal nerve stump encapsulation. Exp Neurol. 2002 Oct. PMID: 12429185
- Akiyama Y, Radtke C, Honmou O, Kocsis JD: Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia. 2002 Sep. PMID: 12203389
- Akiyama Y, Radtke C, Kocsis JD: Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci. 2002 Aug 1. PMID: 12151541
- Liu CN, Devor M, Waxman SG, Kocsis JD: Subthreshold oscillations induced by spinal nerve injury in dissociated muscle and cutaneous afferents of mouse DRG. J Neurophysiol. 2002 Apr. PMID: 11929919
- Kocsis JD: New avenues: exploring approaches for gene therapy in the injured spinal cord. J Spinal Cord Med. 2002 Spring. PMID: 11939459
- Kocsis JD, Akiyama Y, Lankford KL, Radtke C: Cell transplantation of peripheral-myelin-forming cells to repair the injured spinal cord. J Rehabil Res Dev. 2002 Mar-Apr. PMID: 12051471
- Lankford KL, Imaizumi T, Honmou O, Kocsis JD: A quantitative morphometric analysis of rat spinal cord remyelination following transplantation of allogenic Schwann cells. J Comp Neurol. 2002 Feb 11. PMID: 11807836