Tissue Engineering and Regenerative Medicine
Regenerative Medicine, Tissue Engineering and associated disciplines at Imperial College span many Departments in the Faculties of Medicine, Natural Science and Engineering. The Tissue Engineering and Regenerative Medicine Centre (TERM) based at Chelsea and Westminster Hospital was Imperial’s first example of a collaborative enterprise between translational biological research and Material science to stimulate new paradigms in tissue engineering. This was the pioneering enterprise of Dame Julia Polak who, although officially retired, is still active as an Emeritus Professor and has recently been elected to the Steering Committee of the UK Stem Cell Collaboration. The legacy of TERM continues in the Regenerative Medicine Consortium, operating through Interfaculty study groups based around specific tissues (e.g. heart, endoderm, bone) and technologies (Bioprocessing, Imaging) as well as many collaborative links between the key centres in Imperial College such as the Institute for Reproductive and Developmental Biology, the Institute of Biomedical Engineering and the National Heart and Lung Institute. Much of the activity falls within the Imperial College Stem Cell Research Theme. Further details and links to key sites are shown below.
Professor Dame Julia M Polak is the Founder and former head of Imperial College Tissue Engineering and Regenerative Centre (TERM). This is a multidisciplinary and Interfaculty Centre. Professor Dame Julia Polak is presently an Emeritus Professor in the Faculty of Medicine and Imperial College Regenerative Medicine Consortium, Department of Chemical Engineering, Room 144 Roderic Hill Building, South Kensington Campus. Dame Julia also plays an active role in the DTI funded "Stem Cell" project (see under Stem Cell Bioprocessing) and is also involved in other projects with colleagues from different Special Interests Groups. For details of the Special interest groups see later.Commercialisation of Regenerative Medicine research is mostly done via Novathera. Professor Dame Julia Polak is the Founder and Board member of this Imperial spin-out company.She also continues to sit on numerous National and International committees on Regenerative Medicine including the MRC, the BBSRC, the Royal Society and the UKSCF. She remains a wonderful ambassador for Imperial College and is continually invited to give major keynote speeches on the subject. The latest one, in the United States drew an audience of 6000 people. She also continues to receive honors and medals, in recognition of the work she has done over the past 38 years. Part of TERM's research now continues in the Stem Cell and Regenerative Medicine Group based at the Hammersmith Hospital Campus in the Section on Experimental Medicine & Toxicology under the directorship of Professor Martin Wilkins. Please click on the links below to see individual web-pages: Anne Bishop, Helen Rippon, Sile Lane, Siti Ismail, Yuan-Min Lin Part of the Bone Group is now based at South Kensington in a) the Department of Materials with Dr Molly Stevens. Other members of the group are: Dr Nick Evans and Eileen Gentleman. b) Another part of the Bone Group went to the Department of Chemical Engineering with Dr Sakis Mantalaris. Other members of the group are: Marc Placzek, Yu-Shik Hwang , Jae Min Cha, Yunyi Kang
Stem Cell Bioprocessing is a collaboration between Professor Dame Julia Polak, a medically qualified person and stem cell expert and Dr A. Mantalaris, a system engineering, expert on bioreactors and cell encapsulation technologies, (email: a.mantalaris@imperial.ac.uk; web-links: Dr Sakis Mantalaris and Department of Chemical Engineering). The overall aim of this project is the development of bioprocess technology for the successful transfer of laboratory-based practice of stem cells and tissue culture to the clinic as therapeutics, through the application of engineering principles and practices. It aims to have products which are cost effective, rapid in outcome, robust, reliable and reproducible.
The group collaborates closely with many experts throughout Imperial including Professor Tony Cass, sensors (email: t.cass@imperial.ac.uk) and Dr Drakakis: monitoring platform technologies (email: e.drakakis@imperial.ac.uk).
For further details on Chemical Engineering, Biological Systems Engineering Laboratory (BSEL) see email for Dr Mark Placzek (m.r.placzek@imperial.ac.uk) and web-links: Department of Chemical Engineering and www.imperial.ac.uk/bsel
Cardiac Regenerative Medicine is mainly located at the NHLI at the Harefield (Heart Science Centre) and Brompton Campuses. It encompasses work with bone marrow, skeletal myoblast and embryonic stem cells (human and mouse), using cell co-culture and whole models. Tissue engineering to create valve implants, and to combine embryonic stem cells with novel biomaterials for grafting and heart patches development is being done in collaboration with the research group of Dr Aldo R. Boccaccini (email: a.boccaccini@imperial.ac.uk) in the Materials Department of Imperial College. A recent meeting of the Cardiac Regeneration Interfaculty study group, organised by Dr Nadire Ali and Prof Sian Harding on “Stem cells in culture: their differentiation potential and how to manipulate it” drew in expertise from Harefield, NHLI Brompton, the Institute for Reproductive Biology, Bioprocessing and Surgery Departments. A clinical trial to track bone marrow cell implantation is in progress under the direction of Prof Eric Alton.
First trimester fetal blood and tissues contain abundant MSC. These fetal populations have a number of advantages over adult MSC (greater telomerase and expandability, pluripotency markers, greater differentiative capacity, less immunogenicity) indicating that they are more primitive than adult MSC. fMSC are known to engraft readily, and we have shown that they traffic across the placenta and engraft in the bone marrow of every pregnant women. Bioluminescent models show that these cells contribute to tissue repair in post-reproductive females. We are currently investigating the therapeutic potential of hfMSC as an allogeneic or autologous source of cells for intrauterine protein or gene delivery, particularly in early onset genetic mesenchymal deficiency disease and inborn errors of metabolism. Experience in wild type and muscular dystrophy models attributes low-level engraftment and site-specific differentiation to the lack of tissue injury, but preliminary data in skeletal dsyplasia models shows higher engraftment rates associated with phenotypic improvement. The main focus of our work is characterising and optimising the contribution of fMSC to tissue repair, and our chief intramural collaborators are G Bou-Gharios, J Morgan, H Mehmet, G Williams, I Roberts & D Wells.
Regenerative Strategies for Liver
Advances in stem cell biology and the discovery of pluripotent stem cells have made the prospect of cell therapy and tissue regeneration a possible clinical reality. At Hammersmith Hospital we have isolated, from mobilised and leukapheresed blood, a morphologically and phenotypically homogeneous population of CD34+ cells that exhibits the necessary properties. We have demonstrated that these cells (Omnicytes) express genes corresponding to stem cells, haemopoietic, hepatic, cardiac and neuronal cell differentiation. This growing body of research has been a joint project led by Professor Nagy Habib (Department of Surgery) and Professor Myrtle Gordon (Department of Haematology). Work performed on-site as well as at collaborating institutes has shown homing and engraftment to tissue injury along with functional improvement. Furthermore, a phase I safety, toxicity and feasibility clinical study in patients with hepatic insufficiency has been carried out at the Hammersmith. The treatment proved to be safe and no obvious toxicity was observed. This study documented the existence of stem cells that can be directly and reproducibly isolated from an accessible in vivo source and have considerable promise for clinical application. We are currently expanding our spectrum of clinical interest both at the basic/in vivo level as well as the clinical trial level.
Group Head: Kishore Bhakoo (kishore.bhakoo@imperial.ac.uk)
The Group: Zarinah Agnew, Valerie, Bonnelle, Catherine Chapon, Trevor Da Cruz, Valentina Doria, Hamlata Dewchand, William Doward, Victoria Geenes, Johanna Jackson, William Jones
Stem cell research is undergoing a critical transition from being a discipline of the basic sciences to being recognized as a potential component of medical practice. Cell transplants to replace cells lost due to injury or degenerative diseases, for which there are currently no cures, are being pursued in a wide range of experimental models. The monitoring of cellular grafts, non-invasively, is an important aspect of the ongoing efficiency and safety assessment of cell-based therapies. Magnetic resonance imaging methods are potentially well suited for such an application as they produce non-invasive "images" of opaque tissues. For transplanted stem cells to be visualised and tracked by MRI, they need to be tagged so that they are ‘MR visible’. We are developing and implementing a programme of molecular imaging in pre-clinical models that is directed towards improving our understanding of stem cell migration in the context of the whole organism. In order to achieve these goals we are engineering novel MRI contrast agents and developing specific tagging molecules to deliver efficient amounts of contrast agents into stem cells. The intracellular contrast agents are based on either paramagnetic nanoparticles, such as dextran-coated iron oxide, or other MR contrast agents. Methods for monitoring implanted stem cells non-invasively in vivo will greatly facilitate the clinical realization and optimization of the opportunities of stem cell based therapies.
The specific aims of the programme are:
1. To engineer polymer-enveloped super-paramagnetic nanoparticles to deliver efficient amounts of MR contrast agents to cells, achieving intracellular retention, efficient relaxivity, high in vivo MR signal-to-noise ratios and tolerable toxicity levels.
2. To develop generic methodologies for the tracking of cells in vivo using magnetic resonance imaging. The following models will be used:
- glial progenitors implanted in various models: (Multiple Sclerosis, Spinal Cord Repair, Developmental Fate)
- neuronal stem cells implanted in models: (Parkinson’s Disease, Stroke)
- track inflammatory cells involved in: Allergic response in lungs, CNS inflammation, host vs Graft rejection
- cardiac stem cells and progenitors implanted in ischemic heart
