Combined immunosuppressive agents or CD4 antibodies prolong survival of human neural stem cell grafts and improve disease outcomes in amyotrophic lateral sclerosis transgenic mice

Stem Cells
Jun YanVassilis E Koliatsos

Abstract

Amyotrophic lateral sclerosis (ALS) is a target for cell-replacement therapies, including therapies based on human neural stem cells (NSCs). These therapies must be first tested in the appropriate animal models, including transgenic rodents harboring superoxide dismutase (SOD1) mutations linked to familial ALS. However, these rodent subjects reject discordant xenografts. In the present investigation, we grafted NSCs from human embryonic spinal cord into the ventral lumbar cord of 2-month-old SOD1-G93A transgenic mice. Animals were immunosuppressed with FK506, FK506 plus rapamycin, FK506 plus rapamycin plus mycophenolate mofetil, or CD4 antibodies. With FK506 monotherapy, human NSC grafts were rejected within 1 week, whereas combinations of FK506 with one or two of the other agents or CD4 antibodies protected grafts into end-stage illness (i.e., more than 2 months after grafting). The combination of FK506 with rapamycin appeared to be optimal with respect to efficacy and simplicity of administration. Graft protection was achieved via the blockade of CD4- and CD8-cell infiltration and attenuation of the microglial phagocytic response from the host. Surviving NSCs differentiated extensively into neurons that began to establish net...Continue Reading

References

Apr 1, 1985·Experimental Neurology·J R WrathallF Harvey
Feb 1, 1995·Journal of Neurotrauma·D M BassoJ C Bresnahan
Apr 1, 1994·The Journal of Comparative Neurology·V E KoliatsosD L Price
Jun 19, 1998·Brain Research. Molecular Brain Research·D ItoS Kohsaka
Nov 21, 2001·Nature Reviews. Neuroscience·D W Cleveland, J D Rothstein
May 2, 2002·The European Journal of Neuroscience·Carrie B HurelbrinkRoger A Barker
May 29, 2003·Current Drug Targets. CNS and Neurological Disorders·Alexa Klettner, Thomas Herdegen
Jun 13, 2003·Neuroreport·Patrick WeydtThomas Möller
Jul 2, 2003·Molecular Immunology·Marwan A Masri
Mar 17, 2004·Current Opinion in Pharmacology·Yu-Tzu Tai, Clive N Svendsen
Apr 20, 2004·Journal of Cellular and Molecular Medicine·Bozena KaminskaMalgorzata Zawadzka
Jun 26, 2004·Annual Review of Neuroscience·Lucie I BruijnDon W Cleveland
Jul 13, 2004·Lancet·Vincenzo SilaniElio Polli
Feb 16, 2005·Archives of Neurology·Peiying LiMichael E Selzer
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Roger A Barker, Håkan Widner
Apr 23, 2005·The European Journal of Neuroscience·Carrie B Hurelbrink, Roger A Barker
May 6, 2005·Human Gene Therapy·Sandra M KleinClive N Svendsen

❮ Previous
Next ❯

Citations

Sep 10, 2011·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Genevieve Gowing, Clive N Svendsen
Mar 2, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Laura FerraiuoloBrian K Kaspar
Oct 22, 2008·Nature Neuroscience·Angelo C LeporeNicholas J Maragakis
Feb 23, 2011·Tissue Engineering. Part B, Reviews·Mindan WangFuzhai Cui
May 12, 2012·Stem Cell Research & Therapy·Harold S Bernstein, William C Hyun
Aug 27, 2009·Biologics : Targets & Therapy·Steven J Greco, Pranela Rameshwar
Jan 16, 2008·Expert Opinion on Biological Therapy·Vassilis E KoliatsosJun Yan
Aug 12, 2009·Expert Opinion on Biological Therapy·Letizia MazziniFranca Fagioli
Jul 9, 2008·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Stacey A SakowskiEva L Feldman
Mar 13, 2014·Experimental Neurology·Gretchen M ThomsenClive N Svendsen
Jun 16, 2009·Journal of Neuroscience Methods·Olivier LiardEmmanuel Moyse
May 30, 2009·Journal of Neuroimmunology·Maya N HatchHans S Keirstead
Dec 17, 2008·Experimental Neurology·Svitlana Garbuzova-Davis, Paul R Sanberg
Mar 11, 2008·Trends in Neurosciences·Masatoshi Suzuki, Clive N Svendsen
Dec 17, 2008·Biotechnology Journal·Carsten W Lederer, Niovi Santama
Mar 9, 2007·Biotechnology Journal·Carsten W Lederer, Niovi Santama
Jul 9, 2010·Neuropathology and Applied Neurobiology·F DehghaniN P Hailer
Sep 10, 2011·Annals of Neurology·J Simon LunnEva L Feldman
Jul 1, 2009·Journal of Neuroscience Research·Kazunori MiyazakiKoji Abe
Nov 26, 2015·Cell Regeneration·Zhijuan MaoHong Chen
Mar 18, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Stephen A GoutmanEva L Feldman
Oct 4, 2006·Neuron·Séverine BoilléeDon W Cleveland
Sep 21, 2007·Mechanisms of Development·Anthony VuglerPeter Coffey
Jun 10, 2011·Neurosurgery·Nicholas Boulis, Thais Federici
Aug 29, 2013·Stem Cells Translational Medicine·Christopher J SontagBrian J Cummings

❮ Previous
Next ❯

Related Concepts

Related Feeds

ALS: Phenotypes

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized phenotypically by progressive muscle weakness. Clinical phenotypes of ALS can be classified based on the pattern, level, and area of onset (e.g. bulbar, cervical, lumbar). Here is the latest research investigating phenotypes of ALS.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.