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Neurogenesis & Neural Transplantation Laboratory

Regenerative Therapies for Brain Repair

The Thompson laboratory is interested in the idea that stem cells can repair the damaged brain. There are two broad strategies we are pursuing. The first is neural transplantation. It is an approach that has had some success clinically for Parkinson’s disease and involves the transplantation of new neurons directly into the patient’s brain in order to functionally compensate for those lost to the disease. We are continuing to explore and optimise this as a therapeutic option not only for Parkinson’s disease but also for other neurological conditions such as stroke and motor neuron disease. The second strategy is based on the idea that the brain retains some capacity for ‘self-repair’ through neurogenesis. Part of our research program seeks to characterise the brain’s own capacity to generate new neurons in response to injury and to manipulate this response in favour of therapeutic outcomes.

Neurogenesis

For a long time, it was thought the adult brain lacked the capacity to generate new neurons. We now know that adult neurogenesis occurs in very restricted regions in the mammalian brain throughout life and may become compromised in age-related neurological conditions. This has lead to the idea that neurogenesis can be manipulated to facilitate 'brain repair' after injury or stimulated to offset age-related cognitive decline.

Neural Transplantation

Our laboratory is pursuing a number of projects that seek to understand the capacity for neurons generated from human stem cells to structurally and functionally replace neuronal circuitry after intra-cerebral transplantation. This may lead to therapies that restore function to patients with neurological conditions arising from injury or brain disease.

About U

A combined cell and gene therapy approach for homotopic reconstruction of midbrain dopamine pathways using human pluripotent stem cells

Niamh Moriarty, Carlos W Gantner, Cameron PJ Hunt, Charlotte M Ermine, Stefano Frausin, Serena Viventi, Dmitry A Ovchinnikov, Deniz Kirik, Clare L Parish, Lachlan H Thompson

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highlights

Current Lab Members

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Prof. Lachlan Thompson

Principle Investigator

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Dr. Stefano Frausin

Post-Doctoral Researcher

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Dr. Charlotte Ermine

Post-Doctoral Researcher

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Dr. Serena Viventi

Post-Doctoral Researcher

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Mong Tien

Research Assistant

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Brianna Xuereb

Research Assistant

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Jennifer Jin

Research Assistant

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Tyra Fraser

PhD Student

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Georgia Eleftheriou

PhD Student

Lab Alumni

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Jennifer Durnall

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Chris Bye

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Jemima James

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Jordan Wright

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Augustin Cota-Coronado

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Spiros Minas

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Gordon Shao

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Jose Carranceja

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Brett Kegan

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Fahad Somaa

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Chris Turner

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Leela Raonaq

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Ella Van Der Geest

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Raoul Das

Our Lab

Publications

Publications

2022

Warda S, Ermine CE, Khilf MS, Wright D, Brait VH, Nithianantharajah J, Kolbe S, Johnston LA, Thompson LH, Brodtmann A. Long-term structural brain changes in adult rats after mild ischaemic stroke. Brain Communications (2022). July 2022

Moriarty N, Kauhausen JA, Pavan C, Hunt CPJ, de Luzy IR, Penna V, Ermine CM, Thompson LH, Parish CL. Understanding the Influence of Target Acquisition on Survival, Integration, and Phenotypic Maturation of Dopamine Neurons within Stem Cell-Derived Neural Grafts in a Parkinson's Disease Model. Journal of Neuroscience (2022). Jun 2022

Tian P, Elefanty A, Stanley, EG, Durnall JC, Thompson LH, Elwood NJ. Creation of GMP-Compliant iPSCs From Banked Umbilical Cord Blood. Frontiers in Cell and Developmental Biology (2022). Mar 2022

Moriarty N, Gantner CW, Hunt CPJ, Ermine CM, Frausin S, Viventi S, Ovchinnikov DA, Kirik D, Parish CL, Thompson LH. A combined cell and gene therapy approach for homotopic reconstruction of midbrain dopamine pathways using human pluripotent stem cells. Cell Stem Cell (2022). Mar 2022

2021

Hunt CPJ, Penna V, Gantner CW, Moriarty N, Wang Y, Franks S, Ermine CM, de Luzy IR, Pavan C, Long BM, Williams RJ, Thompson LH, Nisbet DR, Parish CL. Tissue Programmed Hydrogels Functionalized with GDNF Improve Human Neural Grafts in Parkinson's Disease. Advanced Functional Materials (2021). Nov 2021

Ermine CM, Nithianantharajah J, O'Brien K, Kauhausen JA, Frausin S, Oman A, Parsons MW, Brait VH, Brodtmann A, Thompson LH.

Hemispheric cortical atrophy and chronic microglial activation following mild focal ischemic stroke in adult male rats. Journal of Neuroscience Research (2021). Oct 2021 

Ermine CM, Chavez CA, Thompson LH. Histological characterization and quantification of newborn cells in the adult rodent brain. STAR Protocols (2021). Sept 2021

de Luzy IR, Law KCL, Moriarty N, Hunt CPJ, Durnall JC, Thompson LH, Nagy A, Parish CL. Human stem cells harboring a suicide gene improve the safety and standardisation of neural transplants in Parkinsonian rats. Nature Communications (2021). May 2021 

Gantner CW, Hunt CPJ, Niclis JC, Penna V, McDougall SJ, Thompson LH, Parish CL. FGF-MAPK signaling regulates human deep-layer corticogenesis. Stem Cell Reports (2021). May 2021

Brait VH, Wright DK, Nategh M, Oman A, Syeda WT, Ermine CM, O'Brien K, Werden E, Churilov L, Johnston LA, Thompson LH, Nithianantharajah J, Jackman KA, Brodtmann A. Longitudinal hippocampal volumetric changes in mice following brain infarction. Scientific Reports (2021). May 2021 

Kagan BJ, Ermine CM, Frausin S, Parish CL, Nithianantharajah J, Thompson LH. Focal ischemic injury to the early neonatal rat brain models cognitive and motor deficits with associated histopathological outcomes relevant to human neonatal brain injury. International Journal of Molecular Sciences (2021). May 2021

Parish CL, Thompson LH. Embryonic stem cells go from bench to bedside for Parkinson's disease. Cell Reports Medicine (2021). Apr 2021

Viventi S, Frausin S, Howden SE, Lim SY, Finol-Urdaneta RK, McArthur JR, Abu-Bonsrah KD, Ng W, Ivanusic J, Thompson LH, Dottori M. In vivo survival and differentiation of Friedreich ataxia iPSC-derived sensory neurons transplanted in the adult dorsal root ganglia. Stem Cells Translational Medicine (2021). Aug 2021

2020

Ermine CM, Wright JL, Stanic D, Parish CL, Thompson LH. Ischemic injury does not stimulate striatal seuron replacement even during periods of active striatal neurogenesis. iScience (2020). Jun 2020

Cota-Coronado A, Durnall JC, Diaz NF, Thompson LH, Diaz-Martinez, NE. Unprecedented Potential for Neural Drug Discovery Based on Self-Organizing hiPSC Platforms. Molecules (2020). Mar 2020

Cota-Coronado A, Thompson LH, Diaz-Martinez NE. Novel pluripotent stem cell lines for enriched grafting in Parkinson's disease. Neural Regen Res. (2020). Feb 2020

Gantner CW, de Luzy IR, Kauhausen JA, Moriarty N, Niclis JC, Penna V, Hunt CPJ, Bye CR, Ermine CM, Pouton CW, Kirik D, Thompson LH, Parish CL. Viral delivery of GDNF improves the functional integration of human pluripotent stem cell- derived dopamine grafts in rodent models of Parkinson’s disease. Cell Stem Cell (2020). Jan 2020

2019

Ermine CM, Somaa F, Wang TY, Kagan BJ, Parish CL, Thompson LH. Long-Term Motor Deficit and Diffuse Cortical Atrophy Following Focal Cortical Ischemia in Athymic Rats. Frontiers in Cellular Neuroscience (2019) Dec 2019;13:552.

 

Bye CR, Penna V, de Luzy IR, Gantner CW, Hunt CPJ, Thompson LH, Parish CL. Transcriptional Profiling of Xenogeneic Transplants: Examining Human Pluripotent Stem Cell-Derived Grafts in the Rodent Brain. Stem Cell Reports (2019) Nov 12;13(5):877-890.

 

de Luzy IR, Niclis JC, Gantner CW, Kauhausen JA, Hunt CPJ, Ermine C, Pouton CW, Thompson LH, Parish CL. Isolation of LMX1a Ventral Midbrain Progenitors Improves the Safety and Predictability of Human Pluripotent Stem Cell-Derived Neural Transplants in Parkinsonian Disease. Journal of Neuroscience (2019). Nov 2019;39(48):9521-9531.

 

Bye CR, Rytova V, Alsanie WF, Parish CL, Thompson LH. Axonal Growth of Midbrain Dopamine Neurons is Modulated by the Cell Adhesion Molecule ALCAM Through Trans-Heterophilic Interactions with L1cam, Chl1, and Semaphorins. Journal of Neuroscience (2019). Aug 2019

 

2018

Wright JL, Chu HX, Kagan BJ, Ermine CM, Kauhausen JA, Parish CL, Sobey CG, Thompson LH. Local injection of endothelin-1 in the early neonatal rat brain models ischemic damage associated with motor impairment and diffuse loss in brain volume. Neuroscience. (2018), Nov 2018.

Nisbet DR, Wang TY, Bruggemann KF, Somma F, Niclis JC, Thompson LH, Parish CL. Shear containment of BDNF within molecular hydrogels promote human stem cell engraftment and post-infarction remodeling in stroke.  Advanced Biosystems (2018), July 2018, 2(9).

Ermine CM, Wright JL, Frausin S, Kauhausen JA, Parish CL, Stanic D, Thompson LH. Modelling the dopamine and noradrenergic cell loss that occurs in Parkinson's disease and the impact on hippocampal neurogenesis, Hippocampus (2018), May; 28(5), 327-337.

Alsanie WF, Niclis JC, Hunt CP, De Luzy IR, Penna V, Bye CR, Pouton CW, Haynes J, Firas J, Thompson LH, Parish CL. Specification of murine ground state pluripotent stem cells to regional neuronal populations. Scientific Reports (2017). Nov 2017; 7(1), 16001.

2017

Alsanie WF,  Penna V, Schachner M, Thompson LH, Parish CL. Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways. Scientific Reports (2017), Aug 24;7(1):9368

Niclis JC, Gantner CW,  Kauhausen JA, Durnall J, Hunt CPJ, Pouton CW, Haynes J, Parish CL*, Thompson LH*. A human Pitx3-GFP embryonic stem cell line reveals the extent and pattern of growth for dopamine and non-dopamine neuronal subtypes following intra-striatal transplantation. Stem Cell Reports (2017), Sep 12; 9(3): 868–882 *equal contribution

doi: 10.1016/j.stemcr.2017.08.002

SomaA FA, Wang TY, Niclis JC, BruggemaN KF, Kauhausen JA, Guo H, McDougall S, Williams RJ, Nisbet DR, Thompson LH, and Parish CL. Peptide-based scaffolds support human pluripotent stem cell-derived neuronal graft integration, neuroprotection and long term functional recovery in a rodent model of stroke. Cell Reports (2017), Aug 22; 20(8), 1964-1977.

doi: doi.org/10.1016/j.celrep.2017.07.069

Niclis JC, Turner C, Durnall J, McDougall S, Kauhausen KA, Leaw B, Dottori M, Parish CL, Thompson LH. Long-distance axonal growth and protracted functional maturation of neurons derived from human induced pluripotent stem cells after intra-cerebral transplantation. Stem Cells Translational Medicine (2017), Jun 6; (6):1547-1556.

doi: 0.1002/sctm.16-0198

Niclis JC, Gantner CW, Alsanie WF, McDougall SJ, Bye CR, Elefanty AG, Stanley EG, Haynes JM, Pouton CW, Thompson LH, Parish CL. Efficiently Specified Ventral Midbrain Dopamine Neurons from Human Pluripotent Stem Cells Under Xeno‐Free Conditions Restore Motor Deficits in Parkinsonian Rodents. Stem Cells Translational Medicine (2017) Mar 6; (3):937-948.

doi: 10.5966/sctm.2016-0073

2016 

Kao T, Labonne T, Niclis JC, Chaurasia R, Lokmic Z, Qian E, Bruveris FF, Howden SE, Motazedian A, Schiesser JV, Costa M, Sourris K, Ng E, Anderson D, Giudice A, Farlie P, Cheung M, Lamande SR, Penington AJ, Parish CL, Thomson LH, Rafii A, Elliott DA, Elefanty AG, Stanley EG. GAPTrap: a Simple Expression System for Pluripotent Stem Cells and their Derivatives. Stem Cell Reports, vol. 7, pg. 518-526.

Wright JW, Ermine CM, Jorgensen JR, Parish CL, Thompson LH. Over-expression of Meteorin drives gliogenesis following striatal injury. Frontiers in Cellular Neuroscience (2016) vol. 10, pg. 177.

Ermine CM, Wright JL, Parish CL, Stanic D, Thompson LH. Combined immunohistochemical and retrograde tracing reveals little evidence for innervation of the rat dentate gyrus from midbrain dopamine neurons. Frontiers in Biology (2016). 11, pages246–255.

2015 

Kauhausen JA, Thompson LH, Parish CL. Chondroitinase improves midbrain pathway reconstruction by transplanted dopamine progenitors in Parkinsonian mice. Molecular and Cellular Neuroscience, vol. 69, pg. 22-9

 

Bye C, Jonsson M, Bjorklund A, Parish P, Thompson LH. Transcriptome analysis identifies transmembrane targets on midbrain dopamine progenitors, PNAS (2015) 112 (15) E1946-E1955

 

Somaa F, Bye C, Thompson LH, Parish C. Meningeal cells influence midbrain development and the engraftment of dopamine progenitors in Parkinsonian mice, Experimental Neurology (2015) May;267:30-41.

2014 

Bird M, Needham K, Frazier AE, van Rooijen J, Leung J, Hough S, Denham M, Thornton ME, Parish CL, Nayagam B, Pera M, Thornburn DR, Thompson LH, Dottori M. Functional characterization of Friedreich Ataxia iPS-derived neuronal progenitors and their integration in the adult brain, PLoS One (2014), 9(7): e101718.

 

Hall H, Reyes S, Landeck N, Bye C, Leanza G, Double K, Thompson L, Halliday G, Kirik D. Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson’s disease, Brain (2014). Sep;137(Pt 9):2493-508.

 

Sahin G, Thompson LH, Lavisse S, Ozgur M, Carta M, Rbah L, Dolle F, Hantraye P, Kirik D. Differential dopamine receptor occupancy underlies L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease, PLoS One (2014). 9(3): e90759.

2013

Wright J, Stanic S, Thompson LH. Generation of striatal projection neurons extends into the neonatal period in the rat brain. Journal of Physiology (2013). vol. 591(Pt 1), pg. 67-76.

 

Kauhausen J, Thompson LH, Parish CL. Cell intrinsic and extrinsic factors contribute to enhance neural circuit reconstruction following transplantation in Parkinsonian mice. Journal of Physiology (2013) vol. 591(Pt 1), pg. 77-91.

 

Reyes S, Fu Y, Double KL, Cottam V, Thompson L, Kirik D, Paxinos G, Watson C, Cooper HM, Halliday GM. Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease. Neurobiology of Aging (2013). vol. 34(3), pg. 873-86.

2012 

Denham M, Bye C, Leung J, Conley B, Thompson LH, Pera M, Dottori M. Glycogen synthase GSK3β and Activin/Nodal Inhibition in Human Embryonic Stem Cells induces a Pre-neuroepithelial State that is required for Specification to a Floor Plate Cell Lineage. Stem Cells (2012) vol.  30(11), pg. 3400-11.

 

Bye CR, Thompson LH, Parish CL (2012), Birth dating of midbrain dopamine neurons identifies A9 enriched tissue for transplantation into Parkinsonian mice, Experimental Neurology (2012). vol. 236(1), pg. 58-68.

 

Denham M, Parish CL, Leaw B, Wright J, Reid CA, Petrou S, Dottori M, Thompson LH. Neurons derived from human embryonic stem cells extend long–distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation. Frontiers in Cellular Neuroscience (2012). Mar 22;6:11.

 

Reyes S, Fu Y, Double K, Thompson L, Kirik D, Paxinos G, Halliday GM. GIRK2 expression in dopamine neurons of the substantia nigra and ventral tegmental area, Journal of Comparative Neurology (2012). vol. 520(12), pg. 2591-607.

 

Jørgensen JR, Fransson A, Fjord-Larsen L, Thompson LH, Houchins JP, Andrade N, Torp M, Kalkkinen N, Andersson E, Lindvall O, Ulfendahl M, Brunak S, Johansen TE, Wahlberg LU. Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo. Experimental Neurology (2012). vol. 233(1), pg. 72-81

2011

Jorgensen JR, Emerich DF, Thompson LH, Torp M, Bintz B, Fjord-Larsen L, Johansen T, Wahlberg LU. Lentiviral delivery of Meteorin protects striatal neurons against excitotoxicity and reverses motor deficits in the quinolinic acid rat model. Neurobiology of Disease, vol. 41(1), pg. 160-8.

2010

Denham M, Thompson LH, Leung J, Pebay A, Bjorklund A, Dottori M. Gli1 is an Inducing Factor in Generating Floorplate Progenitor Cells from Human Embryonic Stem Cells. Stem Cells (2010) vol. 28(10), pg. 1805-15.

 

Grealish S, Jonsson M, Li M, Kirik D, Bjorklund A, Thompson LH. Midbrain Dopamine Neuronal Subtype Composition in Intra-striatal Grafts of Ventral Mesencephalon is an Important Determinant of Functional Efficacy. Brain (2010), vol. 133(2), pg. 482-95.

2009

Thompson LH, Grealish S, Kirik D, Bjorklund A. Reconstruction of the Nigro-striatal Dopamine Pathway in the Adult Mouse Brain, European Journal of Neuroscience (2009) vol. 30(4), no. 625-38.

 

Jonsson ME, Ono Y, Bjorklund A, Thompson LH. Identification of Transplantable Dopamine Neuron Precursors at Different Stages of Midbrain Neurogenesis. Experimental Neurology (2009). vol. 219(1), pg. 341-54.

 

Jørgensen JR, Thompson L, Fjord-Larsen L, Krabbe C, Torp M, Kalkkinen N, Hansen C, Wahlberg L. Characterization of Meteorin-An Evolutionary Conserved Neurotrophic Factor. Journal of Molecular Neuroscience (2009). vol. 39(1-2), pg. 104-16.

 

Friling S, Andersson E, Thompson LH, Jönsson ME, Hebsgaard JB, Nanou E, Alekseenko Z, Marklund U, Kjellander S, Volakakis N, Hovatta O, El Manira A, Björklund A, Perlmann T, Ericson J. Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells, PNAS (2009). vol. 106(18), pg. 7613-8

2008 

Thompson LH, Kirik D, Bjorklund A. Non-dopaminergic neurons in ventral mesencephalic transplants make widespread axonal connections in the host brain. Experimental Neurology (2008). vol. 213(1), pg. 220-8.

 

Irvin DK, Kirik D, Bjorklund A, Thompson LH. In vivo gene delivery to proliferating cells in the striatum generated in response to a 6-hydroxydopamine lesion of the nigro-striatal dopamine pathway. Neurobiology of Disease (2008). vol. 30(3), pg. 343-52.

2006

Thompson L*, Andersson E*, Jensen J, Barraud P, Guillemot F, Parmar M, Bjorklund A Neurogenin2 identifies a transplantable dopamine neuron precursor in the developing ventral mesencephalon. Experimental Neurology (2006). vol. 198(1), pg. 183-98

2005

Barraud P#, Thompson L#, Kirik D, Bjorklund A, Parmar M. In vitro and in vivo properties of Sox1-GFP cells isolated from foetal brain, adult brain or expanded neurosphere culture, European Journal of Neuroscience (2005). vol. 22(7), pg. 1555-69.

 

Thompson L, Barraud P, Andersson E, Kirik D, Bjorklund A. Identification of dopaminergic neurons of nigral and VTA subtypes in grafts of foetal ventral mesencephalon based on cell morphology, protein expression and efferent projections. Journal of Neuroscience (2005). vol. 25(27), pg. 6467-77.

 

Toft Sørensen A, Thompson L, Kirik D, Björklund A, Lindvall O, Kokaia M. Functional properties and synaptic integration of genetically labeled dopaminergic  neurons in intrastriatal grafts. European Journal of Neuroscience (2005). vol. 21(10), pg. 2793-9.

 

Navarro-Galve B, Villa A, Bueno C, Thompson L, Johansen J, Martinez-Serrano A. Gene marking of human neural stem/precursor cells using green fluorescent proteins. Journal of Gene Medicine (2005). vol. 7(1), pg. 18-29.

2004

Jakobsson J, Rosenqvist N, Thompson L, Barraud P, Lundberg C. Dynamics of transgene expression in a neural stem cell line transduced with lentiviral  vectors incorporating the cHS4 insulator. Experimental Cell Research (2004). vol. 298(2), pg. 611-23.

 

Book Chapters and Review Articles

Roger A Barker, Malin Parmar, Agnete Kirkeby, Anders Bjorklund, Lachlan Thompson and Patrik Brundin (2016), Are Stem Cell-Based Therapies for Parkinson’s Disease Ready for the Clinic in 2016?, JPD, vol. 6(1), pg. 57-63.

 

Thompson LH and Bjorklund A (2015), Reconstruction of brain circuitry using neural transplants. Nbiol Dis, vol. 79, pg. 28-40.

 

Parish CL, Thompson LH (2013), Developing stem cell-based therapies for neural repair, Front Cell Neurosci, vol. 7, pg. 198

 

Parish C, Thompson LH (2013), Modulating Wnt signaling to improve cell replacement therapy for Parkinson’s disease, J Mol Cell Biol, vol. 6(1), pg. 54-63.

 

Thompson LH, Parish C (2013), Transplantation of foetal midbrain dopamine progenitors in a rodent model of Parkinson’s disease, Neural Progenitor Cells, vol. 1059, pg. 169-80.

 

Thompson LH, Bjorklund A (2012), Survival, differentiation, and connectivity of ventral mesencephalic dopamine neurons following transplantation, Prog Brain Res, vol. 200, pg. 61-95

 

Thompson LH and Bjorklund A (2009), Transgenic Reporter Mice as Tools for Studies of Transplantability and Connectivity of Dopamine Neuron Precursors in Fetal Tissue Grafts, Prog Brain Res, vol. 175, pg. 53-79.

Current Funding 

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Funding

CONTACT US

Phone: +613 9035 6796

Email: lachlan.thompson@florey.edu.au

Florey Institute of Neuroscience & Mental Health

University of Melbourne

Royal Parade, Parkville

Victoria, Australia

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