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Research Overview

The Stem Cell Medicine Group uses the potential of pluripotent stem cells to create laboratory models of eye and ear diseases to understand disease mechanisms and develop new therapeutic approaches. Our aim is to disseminate and increase translational stem cell research and utilise the great potential of regenerative medicine for childhood disease.

There are currently many incurable childhood diseases, and stem cell approaches offer significant promise towards developing new therapies for these conditions. The stem cell field of research has developed considerably in the last few years with the advent of iPS cells. These are stem cells which are generated from tissues of children or adults, including blood and skin cells. We can then direct the iPS cells to turn into cells that can form tissue and mini-organ structures ("organoids") in the laboratory dish, a process biologists called "differentiation", so they can be used in studies.

This technology provides us with an opportunity to study tissues derived from a patient’s own cells. We have developed differentiation methods to generate retinal and inner ear organoids from iPS cells. We work with organoids as they replicate aspects of normal development and provide unlimited quantities of cells for research. Organoids are also amenable to molecular and imaging approaches.

Dr Anai Gonzalez Cordero leads both the Stem Cell Medicine Group and The Stem Cell and Organoid Facility.

Lab Head

Anai

Anai Gonzalez Cordero

Group Leader, Stem Cell Medicine
Available for Student Supervision

Group Leader, Stem Cell Medicine and Head, Stem Cell & Organoid Facility. If you are interested in joining the Stem Cell Medicine Group or Stem Cell & Organoid Facility, please contact Dr Gonzalez Cordero directly.

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Team Members

Grady Smith
Grady Smith
Research Assistant
Camile Edmilao 1
Camile Edmilao
Research Assistant
Anai Gonzalez Cordero
Michelle O'Hara-Wright
PhD student

Research Projects

Our group's main areas of research involve the differentiation of human iPS cells into retinal and inner ear organoids to understand the development of the human retina and to model diseases.

Understanding human retinogenesis

In the lab, we are interested in using our 3D retinal organoids to understand human retinal development. Of particular interest is the development of cone photoreceptor cells and the events leading to the formation of the cone-rich macular region in humans. Embryonic retinogenesis takes place in a three-dimensional environment, where various cellular, molecular, and electrophysiological cues are spatially and temporally coordinated. More than likely, many of these cues are missing from our current in vitro system. Adding cultures with molecular, electrical, and light-evoked cues to the cultures may increase the utility of the in vitro system in dissecting the detailed events in human retinogenesis.

Modelling of retinal and otic degenerative diseases

Relatively little is known about why photoreceptor and hair cells die in many different degenerative conditions. We seek to understand the mechanisms underlying diseases of the retina and ear as well as develop therapeutic approaches that will slow or prevent the loss of degenerative cells. The approaches we are using include gene therapy and gene editing technologies.

hIPS-derived hair cell & Virally labelled hPSC-derived retinal organoid.


Usher (USH) syndrome

Our projects in this area aim to investigate the pathophysiology of USH syndrome using iPS cells and thus improve our understanding of USH syndrome. Mutations in over 13 genes have been identified to cause USH, especially affecting sensory hair cells and photoreceptors in the inner ear and retina, respectively. The lack of animal models that faithfully replicate the human pathology means that little is known about its pathophysiology and the mechanism of cellular degeneration, hindering the development of new therapies. Currently no treatments are available for the retinal defect and only a limited number of the patients can benefit from cochlear implants. Hair and photoreceptor sensory cells share common structural features, such as cilia and ribbon synapses, and the USH syndromes can therefore be regarded as diseases of cilia ("ciliopathies").

The main objectives of our research are to characterise both retinal and inner ear USH iPS-derived organoids to investigate disease physiology and most importantly to develop new therapeutic approaches, such as gene therapies.

Team Photos

Publications

Use of bioreactors for culturing human retinal organoids improves photoreceptor yields.

Ovando-Roche P., West EL, Branch M.J, Sampson RD, Fernando M, Munro P, Georgiadis A, Rizzi M, Kloc M, Naeem A, Ribeiro J, Smith AJ, Gonzalez-Cordero A and Ali RR. 2018. Stem Cell Research and Therapeutics, 9:156.

Assessment of AAV vector tropisms for mouse and human pluripotent stem cell-derived RPE and photoreceptor cells.

Gonzalez-Cordero A, Goh D, Kruczek K, Naeem A, Fernando M, kleine Holthaus SM, Takaaki M, Blackford SJI, Kloc M, Agundez L, Sampson RD, Borooah S, Ovando-Roche P, Mehat MS, West EL, Smith AJ, Pearson RA, Ali RR. 2018. Human Gene Therapy. 29:10

Transplanted Donor- or Stem Cell-Derived Cone Photoreceptors Can Both Integrate and Undergo Material Transfer in an Environment-Dependent Manner.

Waldron PVW, Marco F, Kruczek K, Ribeiro J, Graca AB, Hippert C, Aghaizu ND, Kalargyrou A, Barber AC, Grimaldi G, Duran Y, Blackford SJI, Kloc M, Goh D, Aldunate EZ, Sampson RD, Bainbridge JWB, Smith AJ, Gonzalez-Cordero A, Sowden JC, Ali RR,and Pearson RA. 2018. Stem Cell Reports; 10(2):406-421.

Recapitulation of Human Retinal Development From Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.

Gonzalez-Cordero A, Kruczek K, Naeem A, Fernando M, Kloc M, Ribeiro J, Goh D, et al. 2017. Stem Cell Reports, 9 (3): 820–37.

Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors Into a Mouse Model of End-Stage Retinal Degeneration.

Kruczek K, Gonzalez Cordero A, Goh D, Naeem A, Jonikas M, Blackford SJI, Kloc M, et al. 2017. Stem Cell Reports; 8 (6): 1659–74.

lsolation and Comparative Transcriptome Analysis of Human Fetal and iPSC-derived Cone Photoreceptor Cells.

Welby E, Lakowski J, Di Foggia V, Budinger D, Gonzalez-Cordero A, Lun ATL, Epstein M, Patel A, Cuevas E, Kruczek K, Naeem A, Minneci F, Hubank M, Jones DT, Marioni JC, Ali RR, Sowden JC. 2017. Cells. Stem Cell Reports. 12;9(6):1898-1915.

Human Stem Cell-Derived Retinal Epithelial Cells Activate Complement via Collectin 11 in Response to Stress.

Fanelli G, Gonzalez Cordero A, Gardner PJ, Peng Q, Fernando M, Kloc M, Farrar CA, et al. 2017. Scientific Reports 7 (1).

Pluripotent stem cells and their utility in treating photoreceptor degenerations.

Aghaizu ND, Kruczek K, Gonzalez-Cordero A, Ali RR, Pearson RA. 2017. Prog Brain Res.;231:191-223.

Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors.

Pearson RA, Gonzalez-Cordero A, West EL, Ribeiro J, Aghaizu ND, Goh D, Sampson RD, Georgiadis A, Waldron PV, Duran Y, Naeem A, Kloc M, Cristante E, Kruczec K, Warre-Cornish K, Sowden JC, Smith AJ and Ali RR. 2016. Nature Communications 7,13029.

Development of an Optimized AAV2/5 Gene Therapy Vector for Leber Congenital Amaurosis Owing to Defects in RPE65.

Georgiadis, A, Duran Y, Ribeiro J, Abelleira-Hervas L, Robbie SJ, Sünkel-Laing B, Fourali S, Gonzalez-Cordero A, Cristante E, Michaelides M, Bainbridge JWB , Smith AJ and Ali RR. 2016. Gene Therapy 23 (12).

Multimodal analysis of ocular inflammation using endotoxin-induced uveitis.

Chu CJ, Gardner PJ, Liyanage SE, Gonzalez-Cordero A, kleine Holthaus SM, Copland DA, Luhmann UFO, Smith AJ, Ali RR, and Dick AD. 2016. Dis Model Mech.,1;9(4):473-81.

Cellular strategies for retinal repair by photoreceptor replacement.

Jayakody SA, Gonzalez-Cordero A, Ali RR, & Pearson RA. 2015. Progress in Retinal and Eye Research, 1–36.

An essential role for LPA signalling in telencephalon development.

Geach TJ, Faas L, Devader C, Gonzalez-Cordero A, Tabler JM, Brunsdon H, Isaacs HV and Dale L. 2014. Development, 141: 940–949.

Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina.

Gonzalez-Cordero A, West EL, Pearson RA, Duran Y, Carvalho LS, Chu CJ, Naeem A, Blackford SJI, Georgiadis A, Lakowski J, Hubank M, Smith AJ, Bainbridge JWB, Sowden JC, Ali RR. 2013. Nature Biotechnology, 31: 741–747.

Defining the integration capacity of embryonic stem cell-derived photoreceptor precursors.

Gonzalez-Cordero A, West EL, Hippert C, Osakada F, Martinez-Barbera JP, Pearson RA, Sowden JC, Takahashi M, Ali RR. 2012b. Stem cells 30: 1424–1435.

Manipulation of the recipient retinal environment by ectopic expression of neurotrophic growth factors can improve transplanted photoreceptor integration and survival.

West EL, Pearson RA, Duran Y, Gonzalez-Cordero A, Maclaren RE, Smith AJ, Sowden JC, Ali RR. 2012a. Cell Transplantation, 21: 871–887

Effective Transplantation of Photoreceptor Precursor Cells Selected Via Cell Surface Antigen Expression.

Lakowski J, Han YT, Pearson RA, Gonzalez-Cordero A, West EL, Gualdoni S, Barber AC, Hubank M, Ali RR, Sowden JC. 2011. Stem cells 29: 1391–1404.