Research

A pluripotent stem cell represents the most primitive cell, from which all different cell types of the body develop. An embryonic stem cell (ES cell) is the best example of this. Human ES cells were first described in 1998 and their potential use in regenerative medicine has gained a lot of attention. These possibilities have become even more evident after the discovery of induced pluripotent stem cells (iPS cells), which can be induced from normal adult cells, such as skin fibroblasts. These cells closely resemble ES cells and they provide an opportunity to generate patient-specific stem cells.  One of the most important potential applications for stem cell based therapies is beta-cell replacement in Type 1 diabetes.
The research area of BSCC focuses in two main sections, human pluripotent stem cells and pancreatic beta-cell biology. More specifically, we are working in the following areas:

1. Interaction of pluripotent stem cells with with extracellular matrix and development of standardized culture conditions based on this
2. Optimization of iPS cell generation from human somatic (patient-derived) cells
3. Comparative studies between hES and hIPS cells, particularly for their differentiation into specific lineages
4. Controlled differentiation of pluripotent stem cells into definitive endoderm and its derivatives (pancreas and liver)
5. Development of disease-specific hepatocyte- and beta cell- models from patient-derived iPS cells
6. Characterization of human islet precursors and mechanisms of their expansion and differentiation
7. Role of EGF-R signalling in beta-cell growth and regeneration
8. Monogenic diseases affecting insulin secretion, particularly congenital hyperinsulinism

 

Selected Publications Within the Last Five Years

Heiskanen AM, Satomaa T, Tiitinen S, Laitinen A, Mannelin S, Mikkola M, Olsson C, Miller-Podraza H, Blomqvist M, Olonen A, Lehenkari P, Tuuri T, Otonkoski T, Natunen J, Saarinen J, Laine J: N-glycolylneuraminic acid xenoantigen contamination of human embryonic and mesenchymal stem cells is reversible. Stem Cells 25:197-202, 2007
Gao R, Ustinov J, Korsgren O, Mikkola M, Lundin K, Otonkoski T: Maturation of in vitro-generated human islets after transplantation in nude mice. Mol Cell Endocrinol 264:28-34, 2007

Gao R, Ustinov J, Korsgren O, Otonkoski T: Effects of immunosuppressive drugs on in vitro neogenesis of human islets. Am J Transp. 7:1021-1026,  2007

Gertow K, Przyborski S, Lorinh JF, Auerbach JM, Epifano O, Otonkoski T, Damjanov I, Ährlund-Richter L: Isolation of human embryonic stem cell-derived teratomas for the assessment of pluripotency. Current Protocols in Stem Cell Biology,  Supplement 3, 1B4.1-1B4.28, 2007

Otonkoski T, Banerjee M, Lundin K: Stem cells as a cure for diabetes. Chapter 14 in: Seino S (Ed) Pancreatic beta cell in health and disease. Springer, Tokyo. pp. 259-278, 2007

Otonkoski T, Jiao  H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, Parton LE, Schuit  F, Quintens R, Sipilä I, Mayatepek E, Meissner T, Halestrap AP, Rutter  GA and Kere J: Physical exercise-induced hypoglycemia  caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells. Am J Hum Genet 81:467-74, 2007.

The International Stem Cell Initiative (ISCI): Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nature Biotechnology 25: 803-816, 2007

Virtanen I, Banerjee M, Palgi J, Korsgren O, Lukinius A, Kikkawa Y, Sekiguchi K, Hukkanen M, Konttinen YT, Otonkoski T: Blood vessels of human islets of Langerhans are surrounded by a double basement membrane. Diabetologia 51:1181-1191, 2008

Paatero AO, Turakainen H, Happonen LJ, Olsson C, Palomäki T, Pajunen MI, Meng X, Otonkoski T, Tuuri T, Berry C, Malani N, Frilander MJ, Bushman FC, Savilahti H: Bacteriophage Mu Integration in Yeast and Mammalian Genomes, Nucleic Acids Res. 2008 Dec;36(22):e148. Epub 2008 Oct 25.

Hanley NA, Piper Hanley K, Miettinen P, Otonkoski T: Weighing up beta cell mass in mice and humans: self renewal, progenitors or stem cell?  Molecular and Cellular Endocrinology, 288:79-85, 2008

Miettinen P, Ormio P, Hakonen E, Banerjee M, Otonkoski T: EGF Receptor in pancreatic beta cell mass regulation. Biochemical Society Transactions, 36(Pt 3):280-285, 2008

Otonkoski T, Banerjee M, Korsgren O, Thornell LE, Virtanen I: Unique basement membrane structure of human pancreatic islets: Implications for beta cell growth and differentiation. Diabetes, Obesity and Metabolism. 10(Suppl.4):119-127, 2008

Billestrup N, Otonkoski T: Dedifferentiation for replication of human beta-cells: a division between mice and men? Diabetes. 2008 Jun;57(6):1457-8.

Vuoristo S, Virtanen I, Takkunen M, Palgi J, Kikkawa Y, Rousselle P, Sekiguchi K, Tuuri T, Otonkoski T: Laminin isoforms in human embryonic stem cells: Synthesis, receptor usage and growth support. J. Cell. Mol. Med.13: 2622-2633, 2009

Satomaa T, Heiskanen AM, Mikkola M, Olsson C, Blomqvist M, Tiittanen M, Jaatinen T, Aitio O, Olonen A, Helin J, Natunen J, Tuuri T, Otonkoski T, Saarinen J, Laine J: The N-glycome of human embryonic stem cells. BMC Cell Biol. 2009 Jun 2;10:42.

Banerjee M, Otonkoski T: A simple two-step protocol for the purification of human pancreatic beta cells.  Diabetologia 52:621-625, 2009.

Närvä E, Autio R, Rahkonen N, Kong L, Rasool O, Dvorak P, Hovatta O, Otonkoski T, Tuuri T, Benvenisty N, Li M, Brüstle O, Baker D, Andrews P, Yli-Harja O, Lahesmaa R: High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity. Nat Biotechnol. 28:371-377, 2010

Laurent LC, Nievergelt CM, Lynch C, Fakunle E, Harness J, Schmidt U, Galat V, Laslett A, Otonkoski T, Keirstead H, Schork A, Park H-S, Loring JF: Restricted ethnic diversity in human embryonic stem cell lines. Nature Methods 7:6-7, 2010.

Rajala K, Lindroos B, Hussein S, Lappalainen RS, Pekkanen-Mattila M, Inzunza J, 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 Derived Stem Cells. PLOS One Apr 19;5(4):e10246, 2010.

Honkanen J, Nieminen JK,Gao R , Luopajarvi K, Salo HM, Ilonen J,  Knip M, Otonkoski T, Vaarala O: IL-17 immunity in human type 1 diabetes. J. Immunol. 185:1959-1967, 2010

Natunen S, Satomaa T, Pitkänen V, Salo H, Mikkola M, Natunen J, Otonkoski T, Valmu L: The binding specificity of the marker antibodies Tra-1-60 and Tra-1-81 reveals a novel pluripotency associated type 1 lactosamine epitope. Glycobiology, 9:1125-1130, 2011

Hussein SM, Batada N, Vuoristo S, Ching RW, Autio R, Närvä E, Ng S, Sourour M, Hämäläinen R, Olsson C, Lundin K, Mikkola M, Trokovic R, Peitz M, Brüstle O, Bazett-Jones DP, Alitalo K, Lahesmaa R, Nagy A and Otonkoski T: Copy number variation and selection during reprogramming to pluripotency. Nature. 2011 Mar 3;471(7336):58-62

Hakonen E, Ustinov J, Mathijs I, Palgi J, Bouwens L, Miettinen P, Otonkoski T: EGF-receptor signaling is needed for murine beta cell mass expansion in response to high fat diet and pregnancy but not after pancreatic duct ligation. Diabetologia 54:1735-43, 2011

Oilinki T, Otonkoski T, Ilonen J, Knip M, Miettinen P: Prevalence and characteristics of diabetes among Somali children and adolescents living in Helsinki, Finland. Pediatr Diabetes. 2011 May 19. doi: 10.1111/j.1399-5448.2011.00783.x. [Epub ahead of print]

Henquin JC, Nenquin M, Sempoux C, Guiot Y, Bellanné-Chantelot C, Otonkoski T, de Lonlay P, Nihoul-Fékété C, Rahier J: In vitro insulin secretion by pancreatic fragments of infants with diazoxide-resistant congenital hyperinsulinism deviates from model predictions. J. Clin. Inv, 121:3932-42, 2011

Hongisto H, Vuoristo S, Mikhailova A, Suuronen R, Virtanen I, Otonkoski T, Skottman H: Laminin-511 expression is associated with the functionality of feeder cells in human embryonic stem cell culture. Stem Cell Res, 2011, in press

 

Page updated November 15, 2011
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