• Ischaemic Stroke Programme

      Sinden John D., Hicks Caroline, Stroemer Paul, Vishnubhatla Indira, and Corteling Randolph.
      Human Neural Stem Cell Therapy for Chronic Ischemic Stroke: Charting Progress from Laboratory to Patients
      Stem Cells and Development. May 2017, ahead of print.


      D.Kalladka, J.D.Sinden, K.Pollock, C.Haig, J.McLean, W.Smith, A.McConnachie, C.Santosh, P.M.Bath, L.Dunn, K.W.Muir. 2016. Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study.  Lancet. 2016 Aug 20;388(10046):787-96

      C. Hicks, L. Stevanato, R. P. Stroemer, E. Tang, S. Richardson and J. D. Sinden. 2013. In vivo and in vitro characterization of the angiogenic effect of CTX0E03 human neural stem cells. Cell Transplant. 22 (9):1541-52. http://www.ncbi.nlm.nih.gov/pubmed/23067568

      E. J. Smith, R. P. Stroemer, N. Gorenkova, M. Nakajima, W. R. Crum, E. Tang, L. Stevanato, J. D. Sinden and M. Modo. 2012. Implantation site and lesion topology determine efficacy of a human neural stem cell line in a rat model of chronic stroke. Stem Cells. 30 (4):785-96. http://www.ncbi.nlm.nih.gov/pubmed/22213183

      J. D. Sinden, I. Vishnubhatla and K. W. Muir. 2012. Prospects for stem cell-derived therapy in stroke. Prog Brain Res. 201 119-67. http://www.ncbi.nlm.nih.gov/pubmed/23186713

      J. D. Sinden and K. W. Muir. 2012. Stem cells in stroke treatment: the promise and the challenges. Int J Stroke. 7 (5):426-34. http://www.ncbi.nlm.nih.gov/pubmed/22712742

      Z. Hassani, J. O’Reilly, Y. Pearse, P. Stroemer, E. Tang, J. Sinden, J. Price and S. Thuret. 2012. Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke. PLoS One. 7 (11):e50444. 3503964.http://www.ncbi.nlm.nih.gov/pubmed/23185625

      S. S. Chen, R. Corteling, L. Stevanato and J. Sinden. 2012. Polyphenols inhibit indoleamine 3,5-dioxygenase-1 enzymatic activity–a role of immunomodulation in chemoprevention. Discov Med. 14 (78):327-33. http://www.ncbi.nlm.nih.gov/pubmed/23200064

      S. Chen, R. Corteling, L. Stevanato and J. Sinden. 2012. Natural inhibitors of indoleamine 3,5-dioxygenase induced by interferon-gamma in human neural stem cells. Biochem Biophys Res Commun. 429 (1-2):117-23. http://www.ncbi.nlm.nih.gov/pubmed/23063682

      K. W. Muir, J. Sinden, E. Miljan and L. Dunn. 2011. Intracranial delivery of stem cells. Transl Stroke Res. 2 (3):266-71. http://www.ncbi.nlm.nih.gov/pubmed/24323648

      D. H. Park, D. J. Eve, P. R. Sanberg, J. Musso, 3rd, A. D. Bachstetter, A. Wolfson, A. Schlunk, M. O. Baradez, J. D. Sinden and C. Gemma. 2010. Increased neuronal proliferation in the dentate gyrus of aged rats following neural stem cell implantation. Stem Cells Dev. 19 (2):175-80. http://www.ncbi.nlm.nih.gov/pubmed/19569872

      P. Stroemer, S. Patel, A. Hope, C. Oliveira, K. Pollock and J. Sinden. 2009. The neural stem cell line CTX0E03 promotes behavioral recovery and endogenous neurogenesis after experimental stroke in a dose-dependent fashion. Neurorehabil Neural Repair. 23 (9):895-909. http://www.ncbi.nlm.nih.gov/pubmed/19633272

      L. Stevanato, R. L. Corteling, P. Stroemer, A. Hope, J. Heward, E. A. Miljan and J. D. Sinden. 2009. c-MycERTAM transgene silencing in a genetically modified human neural stem cell line implanted into MCAo rodent brain. BMC Neurosci. 10 86. 2725042. https://www.ncbi.nlm.nih.gov/pubmed/19622162

      E. A. Miljan and J. D. Sinden. 2009. Stem cell treatment of ischemic brain injury. Curr Opin Mol Ther. 11 (4):394-403. http://www.ncbi.nlm.nih.gov/pubmed/19649984

      D. J. Eve, J. Musso, 3rd, D. H. Park, C. Oliveira, K. Pollock, A. Hope, M. O. Baradez, J. D. Sinden and P. R. Sanberg. 2009. Methodological study investigating long term laser Doppler measured cerebral blood flow changes in a permanently occluded rat stroke model. J Neurosci Methods. 180 (1):52-6. http://www.ncbi.nlm.nih.gov/pubmed/19427529

      P. Stroemer, A. Hope, S. Patel, K. Pollock and J. Sinden. 2008. Development of a human neural stem cell line for use in recovery from disability after stroke. Front Biosci. 13 2290-2. http://www.ncbi.nlm.nih.gov/pubmed/17981710

      R. J. Thomas, A. D. Hope, P. Hourd, M. Baradez, E. A. Miljan, J. D. Sinden and D. J. Williams. 2009. Automated, serum-free production of CTX0E03: a therapeutic clinical grade human neural stem cell line. Biotechnol Lett. 31 (8):1167-72.http://www.ncbi.nlm.nih.gov/pubmed/19343502

      K. Pollock, K and J. Sinden. 2008. Chapter 6. Progressing Neural Stem Cell Lines to the Clinic. In: Y. Shi, D.O. Clegg (eds.) Stem Cell Research and Therapeutics. Therapeutics, 105 © Springer Science + Business Media B.V. 2008: pp.105-122


      H. Hodges, K. Pollock, P. Stroemer, S. Patel, L. Stevanato, I. Reuter and J. Sinden. 2007. Making stem cell lines suitable for transplantation. Cell Transplant. 16 (2):101-15.http://www.ncbi.nlm.nih.gov/pubmed/17474292

      R. Donato, E. A. Miljan, S. J. Hines, S. Aouabdi, K. Pollock, S. Patel, F. A. Edwards and J. D. Sinden. 2007. Differential development of neuronal physiological responsiveness in two human neural stem cell lines. BMC Neurosci. 8 36. 1888696.http://www.ncbi.nlm.nih.gov/pubmed/17531091

      J. D. Sinden. 2006. ReNeuron Group plc. Regen Med. 1 (1):143-7.http://www.ncbi.nlm.nih.gov/pubmed/17465831

      G. Porter, C. Denning, A. Plomer, J. Sinden and P. Torremans. 2006. The patentability of human embryonic stem cells in Europe. Nat Biotechnol. 24 (6):653-5.http://www.ncbi.nlm.nih.gov/pubmed/16763591

      K. Pollock, P. Stroemer, S. Patel, L. Stevanato, A. Hope, E. Miljan, Z. Dong, H. Hodges, J. Price and J. D. Sinden. 2006. A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke. Exp Neurol. 199 (1):143-55.http://www.ncbi.nlm.nih.gov/pubmed/16464451

  • Critical Limb Ischaemia Programme

      R. Katare, P. Stroemer, C. Hicks, L. Stevanato, S. Patel, R. Corteling, E. Miljan, I. Vishnubhatla, J. Sinden and P. Madeddu. 2014. Clinical-grade human neural stem cells promote reparative neovascularization in mouse models of hindlimb ischemia. Arterioscler Thromb Vasc Biol. 34 (2):408-18. http://www.ncbi.nlm.nih.gov/pubmed/24202301

  • Retinal Cells Programme

      J. Luo, P. Baranov, S. Patel, H. Ouyang, J. Quach, F. Wu, A. Qiu, H. Luo, C. Hicks, J. Zeng, J. Zhu, J. Lu, N. Sfeir, C. Wen, M. Zhang, V. Reade, S. Patel, J. Sinden, X. Sun, P. Shaw, M. Young and K. Zhang. 2014. Human retinal progenitor cell transplantation preserves vision. J Biol Chem. 289 (10):6362-71. 3945303. http://www.ncbi.nlm.nih.gov/pubmed/24407289

      S. M. Hasan, A. A. Vugler, E. A. Miljan, J. D. Sinden, S. E. Moss and J. Greenwood. 2010. Immortalized human fetal retinal cells retain progenitor characteristics and represent a potential source for the treatment of retinal degenerative disease. Cell Transplant. 19 (10):1291-306. http://www.ncbi.nlm.nih.gov/pubmed/20447347

      S. Schmitt, U. Aftab, C. Jiang, S. Redenti, H. Klassen, E. Miljan, J. Sinden and M. Young. 2009. Molecular characterization of human retinal progenitor cells. Invest Ophthalmol Vis Sci. 50 (12):5901-8. http://www.ncbi.nlm.nih.gov/pubmed/19553622

      U. Aftab, C. Jiang, B. Tucker, J. Y. Kim, H. Klassen, E. Miljan, J. Sinden and M. Young. 2009. Growth kinetics and transplantation of human retinal progenitor cells. Exp Eye Res. 89 (3):301-10. http://www.ncbi.nlm.nih.gov/pubmed/19524569

  • Exosomes Programme

  • ReNcell products

      Chaudhuri AD, Kabaria S, Choi DC, Mouradian MM, Junn E. MicroRNA-7 promotes glycolysis to protect against 1-methyl-4-phenylpyridinium-induced cell death. J Biol Chem. 2015 Mar 26. pii: jbc.M114.625962. http://www.ncbi.nlm.nih.gov/pubmed/25814668

      Manghera M, Ferguson J, Douville R. ERVK polyprotein processing and reverse transcriptase expression in human cell line models of neurological disease. Viruses. 2015 Jan 20;7(1):320-32. doi: 10.3390/v7010320. http://www.ncbi.nlm.nih.gov/pubmed/25609305

      Gnanasegaran N, Govindasamy V, Musa S, Abu Kasim NH. ReNCell VM conditioned medium enhances the induction of dental pulp stem cells into dopaminergic like cells. Cytotechnology. 2014 Oct 17. http://www.ncbi.nlm.nih.gov/pubmed/25322895

      Choi DC, Chae YJ, Kabaria S, Chaudhuri AD, Jain MR, Li H, Mouradian MM, Junn E. MicroRNA-7 protects against 1-methyl-4-phenylpyridinium-induced cell death by targeting RelA. J Neurosci. 2014 Sep 17;34(38):12725-37. doi: 10.1523/JNEUROSCI.0985-14.2014. http://www.ncbi.nlm.nih.gov/pubmed/25232110

      Meli L, Barbosa HS, Hickey AM, Gasimli L, Nierode G, Diogo MM, Linhardt RJ, Cabral JM, Dordick JS. Three dimensional cellular microarray platform for human neural stem cell differentiation and toxicology. Stem Cell Res. 2014 Jul;13(1):36-47. doi: 10.1016/j.scr.2014.04.004. Epub 2014 Apr 18. http://www.ncbi.nlm.nih.gov/pubmed/24816401

      Mußmann C, Hübner R, Trilck M, Rolfs A, Frech MJ. HES5 is a key mediator of Wnt-3a-induced neuronal differentiation. Stem Cells Dev. 2014 Jun 15;23(12):1328-39. doi: 10.1089/scd.2013.0557. Epub 2014 Mar 25. http://www.ncbi.nlm.nih.gov/pubmed/24548083

      Lemcke H, Kuznetsov SA. Involvement of connexin43 in the EGF/EGFR signalling during self-renewal and differentiation of neural progenitor cells. Cell Signal. 2013 Dec;25(12):2676-84. doi: 10.1016/j.cellsig.2013.08.030. Epub 2013 Sep 4. http://www.ncbi.nlm.nih.gov/pubmed/24012498

      Shahbazi M, Kwang TW, Purwanti YI, Fan W, Wang S. Inhibitory effects of neural stem cells derived from human embryonic stem cells on differentiation and function of monocyte-derived dendritic cells. J Neurol Sci. 2013 Jul 15;330(1-2):85-93. doi: 10.1016/j.jns.2013.04.014. Epub 2013 May 9. http://www.ncbi.nlm.nih.gov/pubmed/23664653

      Díaz-Coránguez M, Segovia J, López-Ornelas A, Puerta-Guardo H, Ludert J, Chávez B, Meraz-Cruz N, González-Mariscal L. Transmigration of neural stem cells across the blood brain barrier induced by glioma cells. PLoS One. 2013 Apr 5;8(4):e60655. doi: 10.1371/journal.pone.0060655. Print 2013. http://www.ncbi.nlm.nih.gov/pubmed/23637756

      Lemcke H, Nittel ML, Weiss DG, Kuznetsov SA. Neuronal differentiation requires a biphasic modulation of gap junctional intercellular communication caused by dynamic changes of connexin43 expression. Eur J Neurosci. 2013 Jul;38(2):2218-28. doi: 10.1111/ejn.12219. Epub 2013 Apr 22. http://www.ncbi.nlm.nih.gov/pubmed/23607708

      Chaudhry ZL, Ahmed BY. Caspase-2 and caspase-8 trigger caspase-3 activation following 6-OHDA-induced stress in human dopaminergic neurons differentiated from ReNVM stem cells. Neurol Res. 2013 May;35(4):435-40. doi: 10.1179/1743132812Y.0000000135. http://www.ncbi.nlm.nih.gov/pubmed/23540413

      Hernández-Benítez R, Vangipuram SD, Ramos-Mandujano G, Lyman WD, Pasantes-Morales H. Taurine enhances the growth of neural precursors derived from fetal human brain and promotes neuronal specification. Dev Neurosci. 2013;35(1):40-9. doi: 10.1159/000346900. Epub 2013 Feb 28. http://www.ncbi.nlm.nih.gov/pubmed/23466467

      Zhao X, Yang Z, Liang G, Wu Z, Peng Y, Joseph DJ, Inan S, Wei H. Dual effects of isoflurane on proliferation, differentiation, and survival in human neuroprogenitor cells. Anesthesiology. 2013 Mar;118(3):537-49. doi: 10.1097/ALN.0b013e3182833fae. http://www.ncbi.nlm.nih.gov/pubmed/23314167

      Jaeger A, Baake J, Weiss DG, Kriehuber R. Glycogen synthase kinase-3beta regulates differentiation-induced apoptosis of human neural progenitor cells. Int J Dev Neurosci. 2013 Feb;31(1):61-8. doi: 10.1016/j.ijdevneu.2012.10.005. Epub 2012 Oct 18. http://www.ncbi.nlm.nih.gov/pubmed/23085082

      Pai S, Verrier F, Sun H, Hu H, Ferrie AM, Eshraghi A, Fang Y. Dynamic mass redistribution assay decodes differentiation of a neural progenitor stem cell. J Biomol Screen. 2012 Oct;17(9):1180-91. Epub 2012 Aug 10. http://www.ncbi.nlm.nih.gov/pubmed/22885730

      Hovakimyan M, Müller J, Wree A, Ortinau S, Rolfs A, Schmitt O. Survival of transplanted human neural stem cell line (ReNcell VM) into the rat brain with and without immunosuppression. Ann Anat. 2012 Sep;194(5):429-35. doi: 10.1016/j.aanat.2012.05.003. Epub 2012 May 22. http://www.ncbi.nlm.nih.gov/pubmed/22683000

      Liedmann A, Rolfs A, Frech MJ. Cultivation of human neural progenitor cells in a 3-dimensional self-assembling peptide hydrogel. J Vis Exp. 2012 Jan 11;(59):e3830. doi: 10.3791/3830. http://www.ncbi.nlm.nih.gov/pubmed/22258286

      Mazemondet O, Hubner R, Frahm J, Koczan D, Bader BM, Weiss DG, Uhrmacher AM, Frech MJ, Rolfs A, Luo J. Quantitative and kinetic profile of Wnt/β-catenin signaling components during human neural progenitor cell differentiation. Cell Mol Biol Lett. 2011 Dec;16(4):515-38. doi: 10.2478/s11658-011-0021-0. Epub 2011 Jul 29. http://www.ncbi.nlm.nih.gov/pubmed/21805133

      Lange C, Mix E, Frahm J, Glass A, Müller J, Schmitt O, Schmöle AC, Klemm K, Ortinau S, Hübner R, Frech MJ, Wree A, Rolfs A. Small molecule GSK-3 inhibitors increase neurogenesis of human neural progenitor cells. Neurosci Lett. 2011 Jan 13;488(1):36-40. doi: 10.1016/j.neulet.2010.10.076. Epub 2010 Nov 5. http://www.ncbi.nlm.nih.gov/pubmed/21056624

      Hübner R, Schmöle AC, Liedmann A, Frech MJ, Rolfs A, Luo J. Differentiation of human neural progenitor cells regulated by Wnt-3a. Biochem Biophys Res Commun. 2010 Sep 24;400(3):358-62. doi: 10.1016/j.bbrc.2010.08.066. Epub 2010 Aug 22. http://www.ncbi.nlm.nih.gov/pubmed/20735988

      Li N, Sarojini H, An J, Wang E. Prosaposin in the secretome of marrow stroma-derived neural progenitor cells protects neural cells from apoptotic death. J Neurochem. 2010 Mar;112(6):1527-38. doi: 10.1111/j.1471-4159.2009.06565.x. Epub 2009 Dec 29. http://www.ncbi.nlm.nih.gov/pubmed/20050969

      Le MT, Xie H, Zhou B, Chia PH, Rizk P, Um M, Udolph G, Yang H, Lim B, Lodish HF. MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets. Mol Cell Biol. 2009 Oct;29(19):5290-305. doi: 10.1128/MCB.01694-08. Epub 2009 Jul 27. http://www.ncbi.nlm.nih.gov/pubmed/19635812

      Morgan PJ, Ortinau S, Frahm J, Krüger N, Rolfs A, Frech MJ. Protection of neurons derived from human neural progenitor cells by veratridine. Neuroreport. 2009 Aug 26;20(13):1225-9. doi: 10.1097/WNR.0b013e32832fbf49. http://www.ncbi.nlm.nih.gov/pubmed/19617853

      Breier JM, Radio NM, Mundy WR, Shafer TJ. Development of a high-throughput screening assay for chemical effects on proliferation and viability of immortalized human neural progenitor cells. Toxicol Sci. 2008 Sep;105(1):119-33. doi: 10.1093/toxsci/kfn115. Epub 2008 Jun 11. http://www.ncbi.nlm.nih.gov/pubmed/18550602

      Beyer S, Mix E, Hoffrogge R, Lünser K, Völker U, Rolfs A. Neuroproteomics in stem cell differentiation. Proteomics Clin Appl. 2007 Nov;1(11):1513-23. doi: 10.1002/prca.200700324. Epub 2007 Oct 16. http://www.ncbi.nlm.nih.gov/pubmed/21136647

      Donato R, Miljan EA, Hines SJ, Aouabdi S, Pollock K, Patel S, Edwards FA, Sinden JD. Differential development of neuronal physiological responsiveness in two human neural stem cell lines. BMC Neurosci. 2007 May 25;8:36. http://www.ncbi.nlm.nih.gov/pubmed/17531091

      Hoffrogge R, Beyer S, Völker U, Uhrmacher AM, Rolfs A. 2-DE proteomic profiling of neuronal stem cells. Neurodegener Dis. 2006;3(1-2):112-21. Review. http://www.ncbi.nlm.nih.gov/pubmed/16909046

      Hoffrogge R, Mikkat S, Scharf C, Beyer S, Christoph H, Pahnke J, Mix E, Berth M, Uhrmacher A, Zubrzycki IZ, Miljan E, Völker U, Rolfs A. 2-DE proteome analysis of a proliferating and differentiating human neuronal stem cell line (ReNcellVM). Proteomics. 2006 Mar;6(6):1833-47. http://www.ncbi.nlm.nih.gov/pubmed/16475233

      Choi SH, Kim YH, Hebisch M, Sliwinski C, Lee S, D’Avanzo C, Chen H, Hooli B, Asselin C, Muffat J, Klee JB, Zhang C, Wainger BJ, Peitz M,Kovacs DM, Woolf CJ, Wagner SL, Tanzi RE, Kim DY. A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature. 2014 Nov 13;515(7526):274-8. doi: 10.1038/nature13800. Epub 2014 Oct 12. http://www.ncbi.nlm.nih.gov/pubmed/25307057

  • Other Publications

      E. A. Miljan, S. J. Hines, P. Pande, R. L. Corteling, C. Hicks, V. Zbarsky, M. Umachandran, P. Sowinski, S. Richardson, E. Tang, M. Wieruszew, S. Patel, P. Stroemer and J. D. Sinden. 2009. Implantation of c-mycER TAM immortalized human mesencephalic-derived clonal cell lines ameliorates behavior dysfunction in a rat model of Parkinson’s disease. Stem Cells Dev. 18 (2):307-19. http://www.ncbi.nlm.nih.gov/pubmed/18554088