6. DISCUSSION
6.4 Concluding remarks
The original aims of these studies were to characterize stem cell specific glycans and glycosyltransferases in UCB derived stem and progenitor cells and to explore the possibility to modify stem cell surface glycosylation by metabolic glycoengineering. By glycosyltransferase gene expression profiling and cell surface analysis we discovered unique features of UCB derived stem cell glycocalyxes, including two novel glycan determinants, extracellular O-GlcNAc and linear
poly-LacNAc on UCB-MSCs. We also discovered that the expression of the common stem cell marker SSEA-3 is affected by cell culture conditions. Furthermore, we characterized a novel interaction between galectin-1 and P-selectin and showed by structural glycan analysis that cell surface glycosylation can be efficiently altered by metabolic glycoengineering. In conclusion, these studies have provided novel insights into the glycobiology of UCB derived stem and progenitor cells that may help to distinguish better cell populations for distinct therapeutic applications and to design therapeutic cells with enhanced biological properties.
ACKNOWLEDGEMENTS
This study was carried out at the Finnish Red Cross Blood Service, Research and Development, Cell Surface Analytics Laboratory in Helsinki, under the supervision of Docent Leena Valmu and Docent Jarkko Räbinä, during the years 2008-2013.
I express my deepest gratitude to all those who made this work possible, especially:
I am grateful to my supervisors Leena and Jarkko for their never ending optimism, for always believing in me and in these projects, and for all the encouragement and support during these years.
I acknowledge the former and present Chief Executives of the Finnish Red Cross Blood Service Martti Syrjälä and Jukka Rautonen, and Directors of the Research and Development Unit Kari Aranko, Jaana Mättö and Jukka Partanen for providing a warm research environment for this work. Saara Laitinen, the Head of Stem Cell Laboratory, is warmly acknowledged for her positive attitude towards these projects, and I want to thank Mike Jones, the Head of Licensing and Alliance Management, for taking care of all the ‘business negotiations’.
I thank Professor Jukka Finne and Docent Susanna Miettinen for the thorough and detailed review of this thesis.
The expert members of the thesis committee Professors Risto Renkonen and Petri Lehenkari are warmly acknowledged for useful discussions and encouragement throughout this thesis project.
I thank my co-authors of the accompanying publications for productive co-operation.
I want to thank the technical staff of the R&D during these years, Teija, Lotta A., Lotta S., Gitta, Sirkka, Iris, Paula, Sisko, Riikka, and Marina for sharing your knowhow, for always finding the time to help me with my mysterious problems, and for all the good laughs and discussions in, and outside, the lab. I also thank Marja-Leena for efficient library services and Pirjo N. for all secretarial assistance.
During these years I got to work with talented and skilful scientists at the R&D labs:
Anita, Annika, Elina, Erja, Harri, Heidi, Ilja, Janne, Jarno, Johanna, Kaarina, Kaija, Karoliina, Lotta K, Milla, Minna, Noora, Pirjo W., Sari, Sofia, Suvi, Tanja K., Tanja H., Tia, Ulla, Virve, and all the others. I want to thank you for the positive atmosphere at R&D, even during the rough times, for great ideas to improve my projects, for helping hands when needed, and for good discussions in and outside the lab. Especially, I want to thank Tia for sharing the ‘never-ending circus’ of the last years of our thesis projects, and Suvi for all the on-line glycohelp and for always being there.
Finally, I want to thank my family and friends for sharing the ups and downs of life and this thesis with me and for all the encouragement during these years. Especially, I thank my parents Sirpa and Kari, and my parents-in law Marja-Leena and Heikki, for their endless support and help with the kids. I thank my beloved husband Teemu for all the love and patience during the thesis process and my three little musketeers Joona, Milja, and Saana for all the sunshine and joy you bring into my everyday life.
This work was financially supported by the Finnish Glycoscience Graduate School, the Finnish Funding Agency for Technology and Innovation (TEKES) and the EVO Medical Research Fund of Finnish Red Cross Blood Service.
Helsinki, April 2014
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