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Complex Organotypic Cell Models

We have developed and investigated 3D cell cultures using: hepatocyte cell lines HepG2, HEPA-RG cells, and human embryonic stem cells. We observed stem cell differentiation toward hepatic progenitors and hepatocytes, but despite positive biomarkers (like albumin), these cells are not yet truly hepatocytes. For example, metabolic enzyme expression is low. In the case of HepG2 and HEPA-RG, we observed a polarized cellular phenotype within cellular spheroids cultured in peptide- and polymer-based nanofiber materials (1, 2). Importantly, we have also generated rigorous methods for 3D imaging of cell spheroids in biomaterials.

Microencapsulated cells may ultimately enable even permanent protein drug therapy with a single administration. Retinal pigment epithelial cell lines (ARPE-19) were cloned to secrete marker protein as well as soluble VEGF-receptor that acts by sequestering free VEGF from tissues. The net effect is to block VEGF activity. We microencapsulated these cells and demonstrated prolonged protein secretion from them (3, 4). This cell therapy research resulted in development and production of a laboratory scale cell microencapsulation device (4) as well as a demonstration of proof-of-principle that cell viability could be preserved in microcapsules during freeze-drying (5). Such methods could facilitate the future logistics for use of polymer-embedded cell therapy products.

Selected Publications:

1. Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. M Bhattacharya, M Malinen, P Lauren, YR Lou, C Parras-Cicuendez , S Kuisma, L Kanninen, M Lille, A Corlu, C Guillozo, A Laukkanen, A Urtti, M Yliperttula.  J Control Release, in press.

2. Peptide nanofiber hydrogel induces formation of bile canalicular structures in 3D cultures of hepatic cell line. M. Malinen, H. Palokangas, M. Yliperttula, A. Urtti.  Tissue Engineering Part A, in press.

3. Kinetic simulation model of protein secretion and accumulation in the cell microcapsules. Wikström J, Syväjärvi H, Urtti A, Yliperttula M. J Gene Med 10: 575-582, 2008.

4. A laboratory scale device for straightforward production of small uniform sized cell microcapsules with long-term cell viability. L. Kontturi, M. Yliperttula, P. Toivainen, A. Määttä, A.M. Määttä, A. Urtti. J Control Rel 152: 136-141, 2011.

5. Viability of human retinal pigment epithelial cells. J. Wikström, M. Elomaa, L., Nevala, J. Räikkönen, A. Urtti, M. Yliperttula. Eur J Pharm Sci 47: 520-526, 2012.

All Publications

Arto Urtti received his Ph.D. in Pharmacy in 1986 (University of Kuopio, Finland). Professor Urtti has led the CDR at the University of Helsinki since 2005. Professor Urtti has authored more than 220 peer-reviewed articles and 20 patents and patent applications. Arto Urtti has received numerous scientific awards including: Innovation Award, American Association of Pharmaceutical Scientists Fellowship, Honorary Membership of the Finnish Pharmacists’ Association, the Albert Wuokko Prize, and the Millennium Distinction Award. He has served as editor-in-chief of the European Journal of Pharmaceutical Sciences and as editorial board member for many other international journals. Professor Urtti’s main research fields include drug delivery (controlled release, computational and cell-based methods for ADME research) and nanotechnology (biomaterial structures for drug and gene targeting and for 3-d cell cultures).

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