BioMediTech Research Groups

Eye Regeneration Group

Group Leader: Associate Professor Heli Skottman

heli.skottman(at)uta.fi

About Us

We are multidisciplinary research group combining expertise in cell biology, genetics, human embryo development, stem cell technology and engineering sciences. Our research interests include severe ophthalmologic diseases, such as age-related macular degeneration (AMD) or diabetic retinopathy, diseases which severely decrease the patients’ quality of life. In addition, severe corneal defects and traumas currently lacks feasible treatment modalities.

Research interests and expertise

The research aim for the team is to develop novel stem cell based tools for the corneal and retinal repair through cell transplantation and ophthalmic in vitro tissue models to increase understanding of the visual system in health and disease.

Our expertise includes use of human pluripotent stem cells (hPSC) for modeling ophthalmic diseases and for studying the functionality of differentiated cells as a cell transplant with novel biomaterials. Patient-derived human induced pluripotent stem cells (hiPSC) we use for modelling the development of retinal diseases especially affecting retinal pigment epithelial cells (RPE). Specifically we use hPSC-RPE technology to study pathogenesis of retinal degeneration including functionality of transporters, dysregulated phagocytosis of photoreceptor outer segments and extracellular matrix remodeling. With this expertise, we aim to discover new molecular disease mechanisms, therapeutic targets, and biomarkers.

Achievements

Our research has demonstrated that hPSC-derived retinal pigment epithelial (RPE) cells resemble their native counterpart by having extensive pigmentation, RPE morphology, expression of RPE specific genes and proteins. These cells are shown to be functional with the ability to phagocytose photoreceptor outer segments in vitro, to form a fully maturated and highly polarized epithelium during prolonged culture, and to express functionally active aquaporin and efflux transporter proteins typical to RPE cells. Moreover, we have shown that the proteome of hPSC-RPE corresponds well with the proteome of the native human RPE. We also continuously strive for developing and optimizing our cell culture and differentiation protocols towards clinical quality for added safety of the cell products, and for enhanced differentiation efficiency.

Our most important recent discovery in cornea research is a novel, efficient and reproducible method to differentiate limbal stem cell type (stem cells responsible for corneal epithelial renewal in the healthy eye) of progenitor cells from hPSC. These cells have a high clinical potential and our long-term aim is to bring these cells towards clinical practice.

Infrastructure

In addition to the research infrastructure available at BioMediTech, our group has established several high quality human embryonic stem cell lines which are available for research purposes under material transfer agreement of the University of Tampere.

Collaboration offer and requests

We have many highly multidisciplinary collaborative research projects with several national and international research groups and together with collaborators we wish to join our expertise with their clinical knowledge in ophthalmology and several different areas of biotechnology and engineering sciences including biomaterial development for retinal and corneal applications, genetic engineering of cells, modeling of tissue regeneration and drug discovery platforms.

Major Publications

  1. Hongisto H, Jylhä A, Nättinen J, Rieck J, Ilmarinen T, Veréb Z, Aapola U, Beuerman R, Petrovski G, Uusitalo H, Skottman H. Comparative proteomic analysis of human embryonic stem cell-derived and primary human retinal pigment epithelium. Sci Rep. 2017 Jul 20;7(1):6016. doi: 10.1038/s41598-017-06233-9.
  2. Mikhailova A, Jylhä A, Rieck J, Nättinen J, Ilmarinen T, Veréb Z, Aapola U, Beuerman R, Petrovski G, Uusitalo H, Skottman H. Comparative proteomics reveals human pluripotent stem cell-derived limbal epithelial stem cells are similar to native ocular surface epithelial cells. Sci Rep. 2015 Oct 1;5:14684. doi: 10.1038/srep14684.
  3. Sorkio A, Vuorimaa-Laukkanen E, Hakola H, Liang H, Ujula T, Valle-Delgado JJ, Österberg M, Yliperttula M, Skottman H. Biomimetic Collagen I and IV double layer Langmuir-Schaeffer films as microenvironment for human pluripotent stem cell derived retinal pigment epithelial cells. Biomaterials. 2015 May;51:257-69. doi: 10.1016/j.biomaterials.2015.02.005. Epub 2015 Feb 20.
  4. Mikhailova A, Ilmarinen T, Uusitalo H, Skottman H. Small molecule induction promotes corneal epithelium cell differentiation from human induced pluripotent stem cells. Stem Cell Reports, 2014. Feb 6;2(2):219-31.
  5. Skottman H, Muranen J, Lähdekorpi H, Pajula E, Mäkelä K, Koivusalo L, Koistinen J, Uusitalo H, Kaarniranta K, Juuti-Uusitalo K. An in vitro outer blood-retinal barrier model based on human embryonic stem cell derived retinal pigment epithelial cells and human endothelial cells. Exp Cell Res. 2017 Oct 1;359(1):101-111. doi: 10.1016/j.yexcr.2017.08.004. Epub 2017 Aug 8.
© 2018 | BioMediTech Finland. All rights reserved.