Journal of Neuroscience Methods 183 (2009) 141–148 Contents lists available at ScienceDirect Journal of Neuroscience Methods journal homepage: www.elsevier.com/locate/jneumeth In vivo multimodal imaging of stem cell transplantation in a rodent model of Parkinson’s disease Johanna Jackson a , Catherine Chapon a , William Jones a , Ella Hirani b , Abdullah Qassim a , Kishore Bhakoo a,∗ a Stem Cell Imaging, MRC Clinical Sciences Centre, Imperial College London, Du Cane Road, London W12 0NN, United Kingdom b Hammersmith Imanet, GE Healthcare, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom article info Article history: Received 6 May 2009 Received in revised form 15 June 2009 Accepted 17 June 2009 Keywords: Stem cell MRI PET Rat Bimodal imaging Mesenchymal abstract Stem cell therapy in the nervous system aims to replace the lost neurons and provide functional recovery. However, it is imperative that we understand the in vivo behaviour of these cells post-implantation. We report visualisation of iron oxide labelled bone marrow-derived stem cells (BMSCs) implanted into the striatum of hemi-parkinsonian rats by magnetic resonance imaging (MRI). Functional efficacy of the donor cells was monitored in vivo using the positron emission tomography (PET) radioligand [ 11 C]raclopride. The cells were visible for 28 days by in vivo MRI. BMSCs provided functional recovery demonstrated by a decreased binding of [ 11 C]raclopride. Although, histology confirmed the persistence of donor cells, no tyrosine hydroxylase positive cells were present. This suggests that BMSCs may have a limited paracrine effect and influence functional recovery. We demonstrate, using multimodal imaging, that we can not only track BMSCs but also establish their effects in a pre-clinical model of Parkinson’s disease. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Neurodegenerative diseases such as Parkinson’s disease (PD) are characterised by cell loss and are thus ideal candidates for stem cell replacement therapy. Although substantial improvements result from the systemic administration of l-DOPA or dopamine agonists, such pharmacological interventions do not address the aetiology of the disease, provide a permanent remedy or prevent progression of the degenerative process (Snyder and Olanow, 2005). Implan- tation of stem cells will provide a more constitutive and relevant solution. This realisation has prompted a renewed interest in stem cells, which may serve as a replenishable source of cells for the treat- ment of neurodegenerative disorders. The neurotoxin, 6-OHDA was used to induce dopaminergic degeneration in the striatum. Whilst other models of PD are available (e.g. MPTP, knock-in mice), this Abbreviations: 6-OHDA, 6-hydroxydopamine; DMEM, Dulbecco’s modified Eagle medium; GFAP, glial fibrillary acidic protein; IB4, Isolectin B4; IODEX-TAT-FITC, dextran coated iron oxide-TAT-fluorescein isothiocyanate; l-DOPA, levadopa; MRI, magnetic resonance imaging; BMSCs, mesenchymal stem cells; PBS, phosphate- buffered solution; PD, Parkinson’s disease; PET, positron emission tomography; TH, tyrosine hydroxylase; USPIO, ultrasmall superparamagnetic iron oxide; VOI, volume- of-interest. ∗ Corresponding author. Current address: Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), #02-02 Helios, 11 Biopo- lis Way, Singapore 138667, Singapore. Tel.: +65 6478 8756/6478 8732 (Office); fax: +65 6478 9957. E-mail addresses: johanna.jackson@med.lu.se (J. Jackson), kishore bhakoo@sbic.a-star.edu.sg (K. Bhakoo). method is more progressive and, in this case, more closely mimics the human form of PD (Schwarting and Huston, 1996b). A clinically relevant strategy may be to implant bone marrow- derived mesenchymal stem cells (BMSCs) that are constitutively capable of neural differentiation and cytokine secretion. Allowing the cells to develop within the PD-affected brains, yields cells whose phenotypes, numbers, locations, and regulation are determined by the interplay of donor elements and the local host milieu. A con- sequence of such donor–host interaction would result in a more pertinent homeostasis. We hypothesized that the BMSCs-based approach might better mitigate some of the limitations of previous strategies, where pre-programmed partially differentiated cells did not provide functional recovery (Brederlau et al., 2006). Further- more, BMSCs can be used as autologous or allogeneic therapies, reducing the need for immunosuppression. They are also relatively easy to harvest in the clinic, with procedures used routinely in bone marrow donations. Due to the seamless integration into the host parenchyma, and migration over long distances, cell grafts cannot be detected based on their mass morphology. To monitor cell migration and positional fate after transplantation, current methods use either reporter genes or chimeric animals. These methods are cumbersome, involve sacrifice of the animal and removal of tissue for histological proce- dures, and cannot be translated to human studies. Furthermore, this approach lacks the temporal analysis of the donor cells, so in practice its uses are limited. Thus, in order to assess the efficacy of stem cell therapies in experimental and clinical studies, there is a need for the development of non-invasive imaging methodolo- 0165-0270/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jneumeth.2009.06.022