Regea s Annual Report 2010

Regea s Annual Report 2010

Publisher: University of Tampere/Regea, Photos: Regea and Sami Helenius,unless indicated otherwise. Layout: Jonna Rinne, Regea Printed by: Hämeen kirjapaino, Tampere, 2011

Contents Foreword 4 Personnel Overview 5 Financial Overview 6 Quality Management 8 Tissue Bank 10 Adult Stem Cell Group 12 Neuro Group 14 Ophthalmology Group 16 Heart Group 18 Publications 20 Regea in Media 27 Regea Personnel 28 3

Foreword For seven years I have been directing Regea, from its infancy until its adulthood. Those years have been very rewarding, but sometimes hard, too. The biggest challenge has been finding funding, because during these years the amount covered by the university has been about one fifth of total funding at its maximum. The year 2010 has been pleasant in Regea. An unparalleled number of PhD theses (five) were finished, and we also managed to get funding for many new research projects. Additionally, Regea frequently got a lot of positive media coverage. In the end of this year, our senior researcher and opthalmology group leader Heli Skottman received the prestigious Academy of Finland Award 2010 for scientific courage. This was a lovely end to this fine year and whole Regea era. During the last year we have successfully continued patient treatments with patients own adipose stem cells and enlarged our area of application from bone defects into other indications, too. The operations at the Regea Tissue Bank have been relatively settled, and our tissue bank cooperates actively with other tissue banks in Finland and abroad. Times change, however, and the university reform both at the Finnish universities in general and at the University of Tampere in particular meant that the year 2010 was the last year when Regea existed as independent institute at the University of Tampere. Next year, Regea is part of the Institute of Biomedical Technology (IBT) that is directed by Docent Hannu Hanhijärvi. My work in Regea will continue, as I will be a member of the board of directors at IBT as well as a member of its management group, and liable for stem cells and tissue engineering, like earlier. For my behalf, I would like to thank warmly our excellent personnel, collaborators and funders for these past seven years. It has been a real pleasure working with you. Our new institute will be even more powerful than before and I expect that its foundation will strengthen our position substantially nationally as well as internationally. I hope that engineering sciences i.e. our collaborators at the Tampere University of Technology also officially join the new joint institute to be founded. Time shows, when it will happen. Tampere, 18th January 2011, Riitta Suuronen, Regea s Director 4

Personnel Overview The year 2010 at the University of Tampere (UTA) was marked by the changes elicited by the organization reform at the university. While the university was at the whirlwind of reforms, the main activities at Regea continued like earlier with approximately the same number of personnel. The organization change at the university meant the establishment of new schools and University Services. Former faculties, departments and institutes were reorganized into nine schools. Starting from the 1 st of January 2011, Regea and the Institute of Medical Technology (IMT) will form the Institute of Biomedical Technology. The institute will be directed by Docent Hannu Hanhijärvi. Regea will be represented at the new institute s board of directors by Riitta Suuronen (deputy member Heli Skottman) and Susanna Miettinen (deputy member Tiia Tallinen). A vast organisation reform concerned the university s administrative, office and IT staff. All university personnel working in these fields will be working for the University Services of UTA from the beginning of January 2011 onwards. The aim of the reform is to support the realization of the new strategy of the University of Tampere as well and as efficiently as possible, and to meet the needs of the new schools. In practice, at the beginning of the year 2011, the administrative staff will continue to work at the same location as earlier despite the organization change, and the changes affecting daily work will be implemented gradually, based on the needs of the new schools. of stem cell research. As for Regea Tissue Bank, it is the only multi-tissue bank in Finland with a strong national position and a significant role in forming the EU-wide instructions concerning eye banking, among other things. In 2010, there were five doctoral dissertations in Regea which is substantially more than in the earlier years. It is (almost) a tradition to invite all the personnel in Regea to the evening party to celebrate the doctoral candidate. The common festivities and the free-time activities, scillfully organized by the recreational committee, have had an important role in addition to the daily routines, and it is hoped that these traditions continue despite the organization reforms. The number of Regea personnel was approximately the same as in the previous year, taking into account the parental leaves. At the end of the year, Regea employed 61 people including PhD students. A part of the researchers were on full-time grants all year. Additionally, 23 students prepared their advanced special studies, final theses or worked as trainees in Regea. Regea employed 21 PhD students at the end of the year. Three of Regea s PhD students studied in the Tampere Graduate Programme in Biomedicine and Biotechnology (TGPBB). The new Collaborative Agreement signed at the beginning of the year changed the conditions of employment slightly. All researchers willl now have a yearly working time (1600 h /year). Former average weekly working hours for laboratory personnel were also changed from 38h 15mins to 36h 15mins, which are the same weekly working hours for the rest of the personnel. Regea s research activities and clinical tissue bank operations continued with approximately the same volumes as in the earlier years. Regea s research activities have reinforced Regea s reputation world-wide as one of the leading institutes 5

Financial Overview Regea s expense budget in 2010 was approximately 3.50 Million euros* and the realized total expenditure was approximately 3.32 Million euros (preliminary data**). The costs realized were 0.18 Million euros lower than estimated. This was due to smaller than expected personnel, travel and laboratory material costs. The realized expenditure was covered according to the figure below (Costs in 2010). The percentages in the figure represent the amount of Regea s total expenditure covered by each funder in 2010. Similarly to the past few years, Regea s biggest funder was Tekes, Finnish Funding Agency for Technology and Innovation, which covered nearly one third of the total funding. The proportion of Regea s own income financing (25.5 %) decreased by 1.5 percentage points from the year 2009. Regea Tissue Bank has had a number of financially challenging years, but it is now starting to cover its expenditures with the sales of tissue transplants and the performing of consulting services. The sales of corneal transplants were smaller than expected, but the sales of amniotic membranes and musculosceletal transplants were higher than expected and thus equalized the turnover. Regea s most important funders in 2010 in addition to Tekes include the Academy of Finland, Pirkanmaa Hospital District, private funders, BioneXt, ITI Foundation, Finnish Foundation for Cardiovascular Research, Finnish Eye and Tissue Bank Foundation and Sokeain Ystävät Foundation. The most significant new funders were Biocenter Finland, Stryker Ltd, and Päivi and Sakari Sohlberg Foundation (figure Income in 2010). Regea s researchers also managed to get personal grants, travel allowances and grants that are not shown in the figure Income in 2010. These grants and allowances were acquired from Pirkanmaa Foundation of the Finnish Cultural Foundation, City of Tampere Science Fund, Dental Society Apollonia, Research Fund of Orion-Farmos, Brain Research Society of Finland, Finnish Nurses Association, Finnish Medical Foundation, Aarne Koskelo Foundation, Income in 2010 Stryker 1.0 % 40 000 Finnish Foundation for Cardiovascular Research 1.2 % 40 000 Biocenter Finland 1.3 % 50 000 ITI Foundation 1.5 % 60 000 Donations 1.8 % 60 000 BioneXt 1.8 % 60 000 Pirkanmaa Hospital District 2.3 % 80 000 Academy of Finland 11.7 % 420 000 Päivikki ja Sakari Sohlberg Foundation 0.9 % 30 000 Finnish Eye and Tissue Bank Foundation 0.7 % 30 000 Sokeain Ystävät Foundation 0.1 %10 000 Tekes 31.8 % 1 130 000 University of Tampere Funding 18.3 % 650 000 Income Financing 25.5 % 910 000 6

and Tampere Graduate Programme in Biomedicine and Biotechnology TGPBB (earlier TGSBB). The distribution of expenses (figure Costs in 2010) is very similar to those of previous years during the start-up years the infrastructure costs were substantially larger. The proportion of personnel expenses exceeded the first time 50 % of total expenses, although the absolute personnel expenses were 0.05 Million euros smaller than in the previous year. In general, all the costs of different cost categories except for the rental costs of premises and equipment were lower than in the previous year. *The administrative costs 0.14 Million euros charged by the University of Tampere have been deducted both from the budgeted and realized costs; correspondingly, a similar deduction has been made from the basic funding of UTA. **At the time of the publication, the financial statement of the University of Tampere has not been completed yet. Costs in 2010 Travel Expenses 1.6 % 50 000 Machinery and Equipment 1.2 % 40 000 Rent (premises and equipment) 13.0 % 430 000 Outsourced Services 15.2 % 510 000 Personnel Expenses 53.3 % 1 770 000 General Expenses, Laboratory Materials and Reagents 15.6 % 520 000 7

Quality Management Regea s quality management consists of practices assuring the quality of research, tissue bank processes, stem cell production, personnel administration and management. Part of Regea s quality management activities are based on legislation or certain standards, while other parts rely on Regea s own objectives and criteria. Regea s quality management is based on the principle that the same people and groups that are responsible for the operation and development of certain activities, are also responsible for the quality assurance and the setting up of quality systems needed for these activities. Regea s quality systems are presented below. Quality Management of Administration and Research Essential practices assuring the quality of administration on the institute level are e.g. systematic orientation of new employees, a detailed specification of each employee s responsibilities, information transfer on matters associated with the department and personnel, and regular surveys on well-being at work. The most important practices assuring the quality of research are regular external assessments of research activities especially in the form of scientific advisory board meetings and research application evaluations by external funders. Information Security Management Information security management in Regea is being built according to ISO27001 standard. The most important matters relating to information security are electronic information security, physical security and personnel training. Quality Management of Tissue Banking and Stem Cell Production (GXP Systems) GXP systems refer to formal quality systems used in the pharmaceutical industry. Their scope and contents are defined in legislation (GLP=Good Laboratory Practice, GMP=Good Manufacturing Practice). GMP principles are applied in Regea s stem cell production activities, when the cells are aimed for clinical use. Regarding clinical tissue banking processes, the legislation concerning tissue establish- ments requires a quality system similar to GMP principles. GXP systems require, for example, an organization chart and specification of responsibilities, precise standard operation procedures for each step of the processes, quality control analyses for materials, products and production environment, documenting of all processes, and complete traceability of employees involved in each step of the processes. In 2010, quality management in Regea focused on performing quality control activities for Regea tissue bank and stem cell production, and on issues associated with the establishment licence and documentation of stem cell treatments. In administration, the focus was on planning and writing instructions for e.g. recruiting, orientation of new employees, grant policies, and practices for employees finishing their work contract or study period in Regea. 8

During next year, the quality management work concentrates on implementing the changes elicited by the organization reform at the university and developing the practices and instructions relating to information security. The quality management of tissue banking and stem cell production focuses primarily on dealing with the regulatory requirements and the quality control work required by the production activities. Several internal and supplier audits will also be performed. All aforementioned also needs to be trained to the relevant personnel, which will also be an important part of the quality management work. Personnel Tiia Tallinen, MSc (Eng.), Quality Manager Quality Control/Tissue Banking and Stem Cell Production Marjo Schutskoff-Jääskeläinen, Bachelor of Laboratory Services (Laboratory Science), Quality Coordinator Helena Närä, Bachelor of Laboratory Services (Laboratory Science), Laboratory Technologist Sari Kalliokoski, Bachelor of Laboratory Services (Laboratory Science), Medical Laboratory Technologist Anna-Maija Honkala, Bachelor of Laboratory Services (Laboratory Science), Laboratory Technologist Juha Heikkilä, Research Assistant Quality Assurance/Administration and Information Security Merja Ahonen-Sihvola, Human Resources Noora Kaipola, BBA, Office Secretary Jonna Rinne, MA, Human Resorces and Marketing (on a leave of absence 03 12/10)) Pasi Vetämäjärvi, BBA, Systems Administrator Documentation and Archiving Personnel and Organization Quality Management System Facilities and Equipment Internal/ External Audits GXP Quality Control Activities Donor Evaluation and Testing Continuous Personnel Training Production Activities Risk Identification and Evaluation 9

Tissue Bank Regea Tissue Bank is a multi-tissue bank recovering, processing, storing and supplying tissue grafts for clinical use. The operating idea of the Regea Tissue Bank is to assure the availability of safe tissues in Finland. The tissue bank aims at enhancing tissue donations and thus meeting the tissue transplant needs of the Finnish hospitals. A new law that was implemented in Finland in August 2010, was promulgated with the aim at increasing organ and tissue donations. This law determines everyone as an organ donor after their death, unless the person has expressed opposing to it while living. Due to the law change, also Regea Tissue Bank started to emphasize the will of the deceased (instead of that of the next of kin) for tissue donations. The topic is discussed in more detail in the editorial of Duodecim (Aalto-Setälä, Duodecim 2010). In 2010, the main fields of Regea Tissue Bank operations were the procurement and supply of musculosceletal tissues (large bones, tendons, total joints and femoral heads), recovering, processing and supplying amniotic membrane and corneal transplants as well as supplying sclera. The processing of bones and tendons was started in the beginning of the year 2011 in cooperation with DIZG, German Institute for Cell and Tissue Replacement. The number of tissues recovered and delivered for clinical use in 2010 is presented on the table on page 11. Coxa Hospital for Joint Replacement operated as procurement organization for femoral heads and Regea for musculo- sceletal tissues. TAUH (138 transplants) and KUH (28) operated as procurement organizations for cornea. A total of 170 amniotic membrane transplants were processed from the amniotic tissues procured from Caesarean operations at TAUH. In 2010, Regea Tissue Bank supplied altogether 561 tissues for clinical use. In addition to hospitals in Pirkanmaa (Tampere Region), tissues were also delivered to several other hospitals and healthcare units in Finland. The supply and demand of corneas were not always aligned during the year. One of the reasons for not always meeting the demand was a greater than expected number of discarded tissues mainly caused by abnormal donor lab results (22 % of the procured cornea). On the other hand, 10 % of the transplants were discarded due to the expired maximum storage time when the demand did not meet the supply. Other reasons for discarding transplants were approximately on the same level as in the earlier years: 18 % of the procured corneas were discarded due to the quality control test results of the transplants, 6% due to the technical problems during procurement, tissue bank processes or in the transplantation operation, and 1 % for other reasons. 43 % of the procured corneas were delivered to the eye clinics of the university hospitals for transplant operations. In addition to banking and supplying tissues, Regea Tissue Bank offers quality system services as well as consulting and auditing services for other Finnish tissue banks. In 2010, Regea Tissue Bank audited (internally) two Finnish tissue banks. Regea Tissue Bank administers the quality systems at the bone banks of Päijät-Häme Central Hospital and Seinäjoki Central Hospital, and starting from the spring of 2011, also 10

the quality system at the bone bank of Central Finland Central Hospital. The bone bank of Reumasäätiö hospital that operated under the Regea quality system was closed down in the spring of 2010. Regea Tissue Bank personnel took part in the national bone bank day organized by the bone bank at Oulu University Hospital, as well as in the annual meetings of the European Tissue Bank Association (EATB) in Berlin, Geremany, and the European Eye Bank Association (EEBA) in Sitges, Spain. Regea Tissue Bank is a non-profit organization. The prices of the tissues supplied by Regea are based on the costs of donor recruiting and testing, tissue procurement, handling, testing and delivery as well as on the costs of the quality assurance required by the authorities. The Finnish Eye Bank Foundation supported Regea s Tissue Bank operations by partly financing the salary of a tissue coordinator. In supplying and processing tissues as well as in developing collaborative European tissue bank practices, Regea Tissue Bank continued its active cooperation with other European tissue establishments. In 2010, Regea Tissue Bank participated in formulating the guidelines of EURO GTPs (European Good Tissue Practices), especially regarding the tissues of the eye and amniotic membrane. The aim of this collaborative European project is at the preparation of common quality assurance practices and a GTP training program for European tissue banks. Group Members Riitta Suuronen, MD, DDS, PhD, Professor, Director Katriina Aalto-Setälä, MD, DDS, Docent, Medical Director of Regea Tissue Bank Annika Hakamäki, PhD, Production Manager (on a leave of absence until 10/10) Hanna Kankkonen, PhD, Production Manager Tiia Tallinen, MSc (Eng.), Quality Manager Katri Hietala, Registered Nurse (operations and anaesthesia), Tissue Coordinator (from 07/10 onwards) Niina Ikonen, Laboratory Technician (until 07/10) Sari Juvonen, Registered Nurse (Ophthalmology), Tissue Coordinator (on a leave of absence from 07/10 onwards) Noora Kailanto, MSc, Pharmacist, Production Coordinator (on a leave of absence from 07/10 onwards) Elina Konsén, Bachelor of Laboratory Services (Laboratory Science), Laboratory Technologist Sari Sarkaniemi, Registered Nurse (Medical Surgical Nursing), Tissue Coordinator Marjo Schutskoff-Jääskeläinen, Bachelor of Health Care, Quality Coordinator Minna Sjöblom, Laboratory Technologist (from 05/10 onwards) The number of tissues procured and delivered by Regea in 2010. Tissue Tissues procured Imported Prosessed Discarded Delivered Femoral heads 151 20 0 19 203 Large bones, tendons, joints 150 58 0 24 172 Cornea 166 0 168 91 79 Amniotic Membrane 3 0 170 10 101 Sclera 0 4 0 0 6 11

Adult Stem Cell Group The research in the adult stem cell group focuses on the characterization of the adult stem cells, the optimization of the growth conditions and the use of these cells in bone, cartilage and soft tissue applications. In each application, the aim is to develop efficient, safe and patient-friendly treatments. The leader of the group is Susanna Miettinen, PhD, who was nominated Docent (Adjunct Professor) in the summer of 2010. In 2010, multipotent stem cells were isolated from fat, wisdom teeth as well as from bone and cartilage samples. The group received fat tissue samples from the Plastic Surgery Unit of Tampere University Hospital (TAUH; MD, PhD Hannu Kuokkanen), wisdom teeth from the Finnish Student Health Service, and bone and cartilage samples from the Pediatric Surgery Unit, Oulu University Hospital (Prof. Willy Serlo). During 2010, the group studied the effect of several growth and physical factors on bone and cartilage differentiation. Growth factors have also been studied in dental stem cell applications, and two manuscripts on the subject have been published. In cooperation with the Department of Biomedical Engineering (BME; Prof. Jari Hyttinen, Prof. Minna Kellomäki) at the TUT and Technical Research Centre of Finland (VTT; MSc Jani Pelto), studies on the effects of electrical and mechanical stimulation on cell growth and differentiation towards bone tissue, have been continued. Moreover, senior researcher Suvi Haimi received a 3-year postdoctoral researcher s funding from the Academy of Finland for the electrical stimulation project. The optimization of stem cell growth conditions has also progressed during 2010, with one manuscript published. Furthermore, a review article concerning the potential of adipose stem cells in regenerative medicine has also been published. Biomaterials are needed in injured tissue to improve cell attachment, their growth and division. In bone and cartilage tissue engineering applications, bioactive glass, beta-tricalcium-phosphate, lactic acid -based polymers, electrically conductive materials and composite structures of these materials have been studied as supporting structures for cells. Biomaterial studies in bone and cartilage research are being performed in collaboration with BME. Two manuscripts have been published in cartilage and bone tissue engineering. Three Master s theses and one advanced special study in bone and cartilage tissue engineering have also been completed (Laura Tirkkonen, Anne Mäntymaa and Janne Säkkinen). In addition, a Master s thesis focusing on the comparison of cell staining methods has been completed in collaboration with the neuro group (Pirjo Arola). Collaboration with the neuro group has also been done in investigating the neuronal differentiation potential of dental stem cells. In soft tissue applications, tissue engineering of fat tissue, skin and uroepithelium was studied. Research samples were received from the Paediatric and Adolescent Surgery and Plastic Surgery Units at TAUH (MD, PhD Tuija Lahdes-Vasama). In these studies, biomaterials such as amniotic membrane and lactic acid based polymers have been investigated, both in cell and animal studies. The uroepithelium project has 12

produced one Master s thesis (Reetta Sartoneva) and one published manuscript this year in collaboration with BME. A few new team members have been enrolled to the group in 2010. PhD student Mimmi Patrikainen has joined the adipose stem cell characterization and culture conditions optimization project. Moreover, MSc student Miina Hämäläinen has joined the bone tissue engineering project and MSc student Rami Pääkkönen has joined the cartilage tissue engineering project. Adipose stem cells have been used in experimental treatments for nine patients during the year 2010. The patient treatments have started at the end of the year 2006, and so far, twenty-six patients have received a new bone transplant in the craniomaxillofacial area utilizing stem cell technology. Furthermore, the first experimental treatments for stress urinary incontinence have been initiated this year. Stem cell treatments have been made using patients own adipose stem cells combined with a biomaterial. Clinical treatments have been carried out in cooperation with Helsinki University Hospital (HUCH) and TUH. The results have been encouraging. One manuscript on the reconstruction of skull defects performed in collaboration with TUH department of neurosurgery (Prof. Juha Öhman) has been accepted for publication. Furthermore, two doctoral theses in the field of oral and maxillofacial surgery have been completed (Ahmed Jan and Roland Männchen). Several collaborative projects are underway. Apart from the previously mentioned partners, the group collaborates with Medical School at the University of Tampere (Prof. Timo Ylikomi); Department of Ear, Nose and Throat Diseases at TUH (MD, PhD Jura Numminen, Prof. Markus Rautiainen); Department of Oral and Maxillofacial Diseases at HUCH (MD, PhD Risto Kontio, MD, PhD Jyrki Törnwall, MD Karri Mesimäki, DDS Jari Mauno and Prof. Christian Lindqvist); Department of Biomedicine at the University of Helsinki (MD, PhD Esko Kankuri) and also with several biomaterials companies (e.g. BonAlive, Synthes, ConMed Linvatec Biomaterials, Straumann and Stryker) as well as with a few biotechnology companies (e.g. Invitrogen and Stem Cell technologies). The group would like to acknowledge the most significant funding sources of its research, Tekes, the Finnish Funding Agency for Technology and Innovation (RAM, Electrocell and StemInClin projects); Pirkanmaa Hospital District; Finnish Cultural Foundation and Pirkanmaa Regional Foundation of the Finnish Cultural Foundation; City of Tampere; Finnish Dental Society Apollonia and Maud Kuistila Memorial Foundation. Group Members Susanna Miettinen, PhD, Docent, Group Leader Riitta Suuronen, MD, PhD, DDS, Professor George Sándor, MD, PhD, DDS, Finland Distinguished Professor Suvi Haimi, PhD, Senior Researcher Bettina Mannerström, PhD, Senior Researcher Jan Wolff, DDS, Dr.med.dent, Senior Researcher Katja Ahtiainen, MSc, Researcher Rashi Khanna-Jain, DDS, Researcher Panu Nordback, BMed, Researcher Mimmi Patrikainen, MSc, Researcher Aliisa Pälli, MSc (Tech.), Researcher Annemari Salonen, DDS, BMed, Researcher Reetta Sartoneva, MSc (Tech.), BMed, Researcher Laura Tirkkonen, MSc, Researcher Annukka Vuorinen, DDS, Researcher Martin Waselau, DDS, Dr.med.vet., Researcher Anna-Maija Honkala, Bachelor of Laboratory Services (Laboratory Science), Laboratory Technologist Miia Juntunen, Bachelor of Laboratory Services (Laboratory Science), Laboratory Technologist and Student Sari Kalliokoski, Bachelor of Laboratory Services (Laboratory Science), Medical Laboratory Technologist Minna Salomäki, MSc, Laboratory Manager Miina Hämäläinen, BSc (Tech.), Student Rami Pääkkönen, BSc, Student Janne Säkkinen, BMed, Student 13

Neuro Group Degenerative diseases and traumas of the central and peripheral nervous systems are the third common cause of long-term disability and death in the Western world. Brain damages and neurodegenerative diseases cause major functional deficits to the patients and even death. Today, there are no effective or curative treatments for these traumas and diseases as the treatments available are only able to relieve the symptoms. Stem cell based therapies provide a promising option to treat these severe deficits in the future. The neuro group focuses on the differentiation of various types of neurons and glial cells from human pluripotent stem cells. In collaboration with clinicians, animal model experts, cell biologists and technical experts the group aims at producing proper neural cell transplants for treating specific neurological deficits. The group also studies the molecular and functional background of human neural cell differentiation and maturation in order to enable in vitro modeling of the human brain. In addition, the functional human neural networks for developmental studies as well as for drug screening and toxicology are developed. The group s main goal in 2010 was to continue the differentiation of homogenous, pure neuronal and glial cell populations for various research applications. The group studied e.g. the viability and differentiation of the cells on different biomaterial scaffolds which could possibly be used in functional transplants or as 3D cell models. The second major goal was to develop a biomimetic environment facilitating the differentiation and measurement of the neural cells in a consortium project with research groups from Tampere University of Technology. The first in vitro model of functional neuronal networks for neurotoxicological studies was developed. The neuro group was responsible for building up Regea s new biomimetic laboratory where the functional properties of the produced neural cells were actively studied. The group published several articles in international journals, and members of the group participated in many international and national meetings with their own presentations. The group s first, Riikka Äänismaa s PhD dissertation was completed in March 2010 and the group leader, PhD Susanna Narkilahti was nominated as Docent (Adjunct Professor) in June 2010. PhD Riikka Äänismaa continued as a senior researcher in the neuro group after her dissertation. MSc Maria Sundberg, MSc (Tech.) Laura Ylä-Outinen, and BMed Heikki Kiiski, continued their PhD projects. Juha Heikkilä (University of Jyväskylä, JyU), Kati Heikkilä (JyU), Anu Hyysalo (JyU), Tiina Joki (UTA), Tiina Kaarela (UTA), Paula Kärnä (JyU), Aliisa Mäkinen (JyU), Meeri Mäkinen (UTA), Hanna Nurmi (UTA), and Ismo Korhonen (TUT) started their theses projects, and Pirjo Arola (TUT) and Laura Ylä-Outinen (TUT) finished their diploma theses. The Academy of Finland funded the project Biomimetic active environment for maturing and differentiating functional neuronal cells and cardiomyocytes from stem cells continuing from the previous year. A new project StemInClin that was funded by Tekes, the Finnish Funding 14

Agency for Technology and Innovation, started. In addition, the neuro research in Regea was funded by Pirkanmaa Hospital District (competitive research funding EVO), Finnish Cultural Foundation and its Pirkanmaa Regional Foundation, Orion-Farmos Research Foundation, Kordelin Foundation, Brain Research Society of Finland, Tamperelaisen tutkimus- työn tukisäätiö ( Tampere research foundation ), Tampere City Science Foundation, Swedish Cultural Foundation, BioneXt Tampere, and a private donation. The group succeeded in getting funding to a new project called SpareBrain from Academy of Finland for years 2011 2013. The group s collaborators included among others Prof. Erik Sundström s research group (Karolinska Institute, Stockholm, Sweden), Prof. Tan Lay Poh s research group (University of Singapore), Prof. Jari Hyttinen s, Prof. Minna Kellomäki s. Prof. Pasi Kallio s, and Prof. Jukka Lekkala s research groups (TUT), Prof. Anu Wartiovaara s and Prof. Timo Otonkoski s research groups (University of Helsinki), and Prof., Chief Physician Irina Elovaara, Associated Prof., Chief Physician Jyrki Tenhunen, and Prof., Chief Physician Juha Öhman (TAUH). Group Members Susanna Narkilahti, Docent, PhD, Senior Researcher, Group Leader Riikka Äänismaa, PhD, Senior Researcher Tuomas Huttunen, MD, Researcher Maria Sundberg, MSc, Researcher Laura Ylä-Outinen, MSc (Tech.), Researcher Heikki Kiiski, BMed, Researcher Maarit Patrikainen, Bachelor of Laboratory Services (Laboratory Science), Laboratory Technologist Hanna Koskenaho, Bachelor of Health Care (Biomedical Laboratory Service), Medical Laboratory Technologist (50 %) Pirjo Arola, BSc, Student Kati Heikkilä, BSc, Student Juha Heikkilä, Student Anu Hyysalo, BSc, Student Tiina Joki, BSc, Student Tiina Kaarela, BSc, Student Paula Kärnä, BSc, Student Aliisa Mäkinen, BSc, Student Meeri Mäkinen, BSc, Student Hanna Nurmi, BSc, Student Ismo Korhonen, BSc (Tech.), Student 15

Ophthalmology Group Human embryonic stem cells (hesc) and maybe also induced pluripotent stem cells (ipsc) are a promising source of cells for tissue engineering applications. For several years, the group has developed novel Good Manufacturing Practice (GMP) -quality culture methods for hescs without any animal-derived components. In addition, the group produces hesc lines used for research at Regea. New hesc lines are derived from surplus embryos donated by voluntary couples after infertility treatments. The embryos would otherwise be discarded. The main objectives for the group are to develop novel cell based tissue engineering methods for the corneal and retinal repair through cell transplantation. Severe ophthalmologic diseases like age-related macular degeneration decrease the quality of life of the patients and the prevalence of retinal diseases will dramatically increase due to the increasing proportion of the elderly people. Currently, there are no effective means to restore or prevent these diseases. One of the most promising means to treat the visual disturbances is by replacing the most critical cell types and/ or restoring their function by the means of cell transplantation. Human pluripotent stem cells (hesc and ipsc) with their tremendous differentiation capacity are an important tool for regenerative medicine as well as for drug discovery. However, new approaches to gain a sufficient amount of differentiated functional cells are needed. The main objective in 2010 was to continue the two ophthalmology related research projects initiated in 2008, the first aiming at the development of novel differentiation methods for pluripotent stem cells towards mature and functional retinal pigment epithelium (RPE) cells and their molecular and functional characterization, and the second aiming at the development of novel methods for the utilization of patient s own oral mucosa epithelial cells for the repair of corneal epithelial defects. The group succeeded in licensing the developed hesc culture medium to Swedish company Vitrolife Ab, and the researcher Kristiina Rajala responsible for this development work defended her PhD thesis in May 2010. The group also studied the role and function of different fibroblast feeder cells in hesc culture. In addition, the group continued to develop a serum-free differentiation method for the production of RPE cell lineages also using ipsc. The emphasis of the research was mainly on the molecular and functional characterization of these cells. The group continued to work for the establishment of serum-free epithelial cell cultures from the oral mucosa biopsies for corneal defects. Academy of Finland gave an Academy of Finland Award 2010 for scientific courage to the group leader Heli Skottman. A new post doc researcher Kati Juuti-Uusitalo started in the group and the Academy of Finland granted her a postdoctoral research project for three years. Other new group members in 2010 were Olli-Pekka Kurkela (Tampere University of Technology) and Alexandra Mikhailova (University of Tampere). In addition, Hanna Koskenaho and Elina Konsén completed their advanced studies in cell and molecular biology at Tampere University of Applied Sciences 16

The main collaborators in 2010 were Prof. Hannu Uusitalo s research group (UTA and TAUH); Prof. Jari Hyttinen s group (TUT); Prof. Minna Kellomäki s group (TUT); Prof. Arto Urtti (Centre for Drug Research, University of Helsinki, UH); Prof. Timo Otonkoski s research group (Stem cell research center, UH); Prof. Kai Kaarniranta (University of Eastern Finland; TAUH/ Opthalmology, Otology and Oral Diseases Unit); Women s Clinic at TAUH), and Ovumia Ltd. The international main collaborators for the group were Prof. François Willermain (Université Libre de Bruxelles, Brussels); Prof. Janos Vörös, (ETH Zurich) and Prof. Robin Ali (University College London, Group Members Heli Skottman, PhD, Docent, Academy of Finland Research Fellow, Group Leader Heli Skottman and Sampsa Hyysalo received Academy of Finland Awards in 2010. Photo: Academy of Finland. and Elina Savioja from Tampere University of Technology finished her Master s thesis. The research was funded by Tekes, the Finnish Funding Agency for Technology and Innovation, the Academy of Finland, the Competitive Research Funding of the Pirkanmaa Hospital District, TGPBB graduate programme of the UTA, two private donations and Päivikki and Sakari Sohlberg foundation. The group utilizes the state-of-the-art knowledge of ophthalmology as well as that of biomedical engineering in Tampere region represented by UTA, TUT and TAUH. SILK, Research and Development Center for Ophthalmic Innovations, is an interdisciplinary knowledge centre for eye diseases, diagnostics and new treatment methods operating in Tampere, and Regea s ophthalmology group is involved in SILK s activities as well. Tanja Ilmarinen, PhD, Senior Researcher Kati Juuti-Uusitalo, PhD, Senior Researcher Heidi Hongisto (née Hakala), MSc., Researcher Hanna Vaajasaari, MSc., Researcher Juhana Laine, Ophthalmology Specialist, Researcher Astrid Subrizi, MSc., Researcher, Viikki/Urtti s group Elina Konsén, Bachelor of Laboratory Services (Laboratory Science), Laboratory Technologist Hanna Koskenaho, Bachelor of Health Care (Biomedical Laboratory Service), Medical Laboratory Technologist Outi Melin, Bachelor of Helath Care, Chief Medical Laboratory Technologist Olli-Pekka Kurkela, Student Alexandra Mikhailova, BSc, Student 17

Heart Group Cardiomyocytes (heart muscle cells) differentiated from stem cells can be used to develop cell and tissue models for studying the development and function of the heart, and for drug development as well as drug safety testing. In addition, cardiomyocytes differentiated from stem cells also have a potential to be used for cell therapy to repair damaged heart tissue in the future. The so-called ips cell technology that has the ability to induce pluripotent stem cells from human adult somatic cells has revolutionized the field of stem cell research. ips cell technology enables the production of patient specific pluripotent stem cell lines and subsequently, the creation of models for genetic heart diseases for studying the pathogenesis and molecular mechanisms underlying the diseases. This offers previously unimagined possibilities for research and for drug development. The most important goal for the heart group is to differentiate functional cardiomyocytes from stem cells and to utilize the ips cell technology for studying the genetic cardiac diseases. The research in the heart group focuses on the development and the optimization of the differentiation methods and the growth environment of cardiomyocytes. This includes studying both the influence of biochemical and physical factors on the differentiation and characteristics of cardiomyocytes. The heart group also develops many methods for the characterization of cardiomyocytes, especially for their functional characterization, such as for the measuring of drug response. During 2010, the heart group focused on the production of patient specific ips cell lines, the characterization of cardiomyocytes and on the development of characterization methods for cardiomyocytes. So far, the group has collected over 50 skin biopsies from patients and has established over 60 ips cell lines from these samples. During 2010, researcher Anna Lahti focused on the establishment of patient specific ips cell lines and especially on the characterization of cardiomyocytes from LQT (Long QT syndrome) patients. Researcher Marisa Ojala continued her PhD project started in 2009 to study and optimize ips cell production and cardiomyocyte differentiation. The heart group did a lot of work on developing the characterization methods for cardiomyocytes. Especially the characterization of the electrical features of the cells is essential in distinguishing the functional differences of patient specific cells, i.e. those cells carrying a mutation and those not carrying one. Researcher Ville Kujala focused in his PhD thesis on the optimization of microelectrode array (MEA) techniques for cardiomyocytes and on the functional characterization of patient specific cardiomyocytes. During the year, electrophysiologist, PhD Kim Larsson was hired to set up and optimize the electro- physiological analysis methods. Together with the researchers at TUT, the heart group continued to develop an active culture and measurement environment for cardiomyocytes. In connection with this project, the influence of physical factors in the cardiomyocyte differentiation and characteristics was studied during the year. Student Kirsi Kujala studied the effect of electricity on the cardiomyocytes in her Master s thesis and researcher 18

Liisa Ikonen studied the effect of mechanical stimulation on cardiomyocytes in her PhD thesis. Ikonen also continued to study the biomaterials suitable for cardiomyocytes. In addition, the heart group participated in the establishment of the ips cell technology service platform operated by Biocenter Finland. During the year, students Maria af Hällström and Markus Haponen conducted their laboratory training and BSc theses and student Jukka Kuusela conducted his Master s thesis in the group. One of the most significant achievements of the year was the establishment and the characterization of several patient specific ips cell lines. One of the most important and glorious events of the year was the PhD defense of Mari Pekkanen-Mattila in November. In addition, the group organized Biocenter Finland s Stem Cells and Biomaterials symposium, where international stem cell scientists were invited as speakers. The second and third publications of the PhD thesis of researcher Mari Pekkanen-Mattila were published. Furthermore, numerous manuscripts were sent for publication and many of the researchers in the group participated in several scientific conferences all over the world. University Hospital), PhD, Docent Tuula Heinonen (FICAM, Finnish Center for Alternative Methods) and Ari-Pekka Koivisto and Hugh Chapman (Orion Ltd.). Group Members Katriina Aalto-Setälä, Group Leader, Docent, Medical Director (Tissue Bank), MD, PhD Erja Kerkelä, PhD, Senior Researcher (until 06/2010) Mari Pekkanen-Mattila, PhD, Senior Researcher Kristiina Rajala, PhD, Senior Researcher Liisa Ikonen, MSc (Tech.), Researcher Ville Kujala, MSc, Researcher Anna Lahti, MSc, Researcher Marisa Ojala, MSc, Researcher Henna Venäläinen, Bachelor of Laboratory Services (Laboratory Science), Laboratory Technologist Maria af Hällström, Student (Laboratory Services) Markus Haponen, Student (Laboratory Services) Jukka Kuusela, BSc, student Kirsi Kujala, BSc (Tech.), Student The research of the heart group in 2010 was funded by e.g. Academy of Finland, Biocenter Finland, Finnish Foundation for Cardiovascular Research, Finnish Cultural Foundation and its Pirkanmaa Regional Foundation, Pirkanmaa Hospital District (competitive research funding EVO), TGPBB (Tampere Graduate Programme in Biomedicine and Biotechnology) and Tekes, the Finnish Funding Agency for Technology and Innovation. Tekes granted extension to its project funding for the heart group in autumn 2010. The most important collaborators of the heart group in 2010 included Prof. Bruce Conklin s and Prof. Shinya Yamanaka s research groups (Gladstone Institute, University of California), Prof. Olli Silvennoinen s research group (UTA), Prof. Jari Hyttinen s, Prof. Pasi Kallio s, Prof. Jukka Lekkala s and Prof. Minna Kellomäki s research groups (TUT), Prof. Kimmo Kontula and MD, PhD, Docent Heikki Swan (Helsinki 19

Publications International Scientific Publications 1. Albilia JB, Humber CC, Clokie CM, Sándor GK. Lemierre syndrome from anodontogenic source: a review for dentists J Can Dent Assoc. 2010;76:a47. 2. Auer S, Lappalainen RS, Skottman H, Suuronen R, Narkilahti S, Vikholm-Lundin I. An antibody surface for selective neuronal cell attachment. J Neurosci Methods 2010;186(1):72-6. 3. Barr T, McNamara AJ, Sándor GK, Clokie CM, Peel SA. Comparison of the osteoinductivity of bioimplants containing recombinant human bone morphogenetic proteins 2 (Infuse) and 7 (OP-1). Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(4):531-40. Epub 2010, Feb 26. 4. Beaumont M, DuVal MG, Loai Y, Farhat WA, Sándor GK, Cheng HL. Monitoring angiogenesis in soft-tissue engineered constructs for calvarium bone regeneration: an in vivo longitudinal DCE-MRI study. NMR Biomed. 2010;23(1):48-55. 5. Bujtár P, Sándor GK, Bojtos A, Szucs A, Barabás J. Finite element analysis of the human mandible at 3 different stages of life. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110(3):301-9. Epub 2010, May 1. 6. Cloutier M, Girard B, Peel SA, Wilson D, Sándor GK, Clokie CM, Miller D. Calvarial bone wound healing: a comparison between carbide and diamond drills, Er:YAG and Femtosecond lasers with or without BMP-7. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110(6):720-8. Epub 2010, Jul 24. 7. Haaparanta AM, Haimi S, Ellä V, Hopper N, Miettinen S, Suuronen R, Kellomäki M. Porous polylactide/beta-tricalcium phosphate composite scaffolds for tissue engineering applications. J Tissue Eng Regen Med 2010; 4(5)366-73. 8. Ho SK, Peel SA, Hu ZM, Sándor GK, Clokie CM. Augmentation of the maxillary sinus: comparison of bioimplants containing bone morphogenetic protein and autogenous bone in a rabbit model. J Can Dent Assoc. 2010;76:a108. 9. Hu Z, Peel SA, Ho SK, Sándor GK, Su Y, Clokie CM. The expression of bone matrix proteins induced by different bioimplants in a rabbit sinus lift model. J Biomed Mater Res A. 2010;95(4):1048-54. doi: 10.1002/jbm.a.32911. Epub 2010, Sep 28. 10. Humber CC, Sándor GK, Davis JM, Peel SA, Brkovic BM, Kim YD, Holmes HI, Clokie CM. Bone healing with an in situ-formed bioresorbable polyethylene glycol hydrogel membrane in rabbit calvarial defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(3):372-84. Epub 2010, Jan 8. 11. Jan A, Sándor GK, Brkovic BB, Peel S, Kim YD, Xiao WZ, Evans AW, Clokie CM. Effect of hyperbaric oxygen on demineralized bone matrix and biphasic calcium phosphate bone substitutes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(1):59-66. Epub 2009, Oct 20. 12. Ketola-Kinnula T, Suuronen R, Kontio R, Laine P, Lindqvist C. Bioabsorbable plates and screws for fixation of mandibulotomies in ablative oral cancer surgery. J Oral Maxillofac Surg 2010; 68(8):1753-62. 13. Khanna-Jain R, Agata H, Vuorinen A, Sándor GK, Suuronen R, Miettinen S. Addition of BMP-2 or BMP-6 to dexamethasone, ascorbic acid, and β-glycerophosphate may not enhance osteogenic differentiation of human periodontal ligament cells. Growth Factors 2010; 28(6):437-46. Epub 2010, Jun 23. 20

14. Khanna-Jain R, Vuorinen A, Sándor GK, Suuronen R, Miettinen S. Vitamin D(3) metabolites induce osteogenic differentiation in human dental pulp and human dental follicle cells. J Steroid Biochem Mol Biol 2010;122(4):33-41. 15. Lappalainen RS, Salomäki M, Ylä-Outinen L, Heikkilä TJ, Hyttinen JA, Pihlajamäki H, Suuronen R, Skottman H, Narkilahti S. Similarly derived and cultured hesc lines show variation in their developmental potential towards neuronal cells in long-term culture. Regen Med 2010;5(5): 749-62. 16. Lindfors LT, Tervonen EA, Sándor GK, Ylikontiola LP. Guided bone regeneration using a titanium-reinforced eptfe membrane and particulate autogenous bone: the effect of smoking and membrane exposure. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(6): 825-30. 17. Lindroos B, Aho KL, Kuokkanen H, Räty S, Huhtala H, Lemponen R, Yli-Harja O, Suuronen R, Miettinen S. Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum. Tissue Eng Part A 2010;16(7):2281-94. 18. Lindroos B, Suuronen R, Miettinen S. The Potential of Adipose Stem Cells in Regenerative Medicine. Stem Cell Rev 2010, Sep 18. [Epub ahead of print] 19. Liu Z, Vuohelainen V, Tarkka M, Tenhunen J, Lappalainen RS, Narkilahti S, Paavonen T, Oksala N, Wu Z, Mennander A. (2010) Glutamate release predicts ongoing myocardial ischemia of rat hearts. Scand J Clin Lab Invest 2010;70(3):217-24. 20. Mäenpää K, Ellä V, Mauno J, Kellomäki M, Suuronen R, Ylikomi T, Miettinen S. Use of adipose stem cells and polylactide discs for tissue engineering of the temporomandibular joint disc. J R Soc Interface 2010;6;7(42):177-88. Epub 2009, May 27. 21. Pekkanen-Mattila M, Chapman H, Kerkelä E, Suuronen R, Skottman H, Koivisto AP, Aalto-Setälä K. Human embryonic stem cell-derived cardiomyocytes: demonstration of a portion of cardiac cells with fairly mature electrical phenotype. Exp Biol Med (Maywood) 2010;235(4):522-30. 22. Pekkanen-Mattila M, Pelto-Huikko M, Kujala V, Suuronen R, Skottman H, Aalto-Setälä K, Kerkelä E. Spatial and temporal expression pattern of germ layer markers during human embryonic stem cell differentiation in embryoid bodies. Histochem Cell Biol 2010;133(5):595-606 Epub 2010, Apr 6. 23. Pekkanen-Mattila, M., Chapman, H., Kerkelä, E., Suuronen, R., Skottman, H., Koivisto, A-P., Aalto-Setälä, K. Production of human embryonic stem cell-derived cardiomyocytes with electrophysiological maturity -comparison of two different cardiac differentiation methods. Exprimental biology and medicine. 2010;235(4):522 30. 24. Pelto J, Haimi S, Puukilainen E, Whitten PG, Spinks GM, Bahrami-Samani M, Ritala M, Vuorinen T. Electroactivity and biocompatibility of polypyrrole-hyaluronic acid multi-walled carbon nanotube composite. J Biomed Mater Res A. 2010;93(3):1056-67. 25. Rajala K, Lindroos B, Hussein SM, Lappalainen RS, Pekkanen-Mattila M, Inzunza J, Rozell B, Miettinen S, Narkilahti S, Kerkelä E, Aalto-Setälä K, Otonkoski T, Suuronen R, Hovatta O, Skottman H. A defined and xeno-free culture method enabling the establishment of clinical-grade human embryonic, induced pluripotent and adipose stem cells. PLoS One 2010;5(4):e10246 26. Sándor GK, Carmichael RP, Brkovic BM. Dental implants placed into alveolar clefts reconstructed with tongue flaps and bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(2):e1-7. 21