Fredrik Lanner

Fredrik Lanner, researcher at the Department of Clinical Science, Intervention and Technology and the Ming Wai Lau Centre for Reparative Medicine at Karolinska Institutet.
Photo: Ulf Sirborn

Assistant Professor Fredrik Lanner undertook his PhD thesis at the department of Cell and Molecular Biology Karolinska Institutet followed by postdoctoral research in Janet Rossants lab at The Hospital for Sick Children, Toronto. Having returned to Karolinska Institutet, Sweden, he has established his independent research lab exploring how pluripotent stem cells are regulated in the human embryo and how we best could use embryonic stem cells in stem cell based reparative medicine.

To start exploring early human development and pluripotency the Lanner lab performed a single cell transcriptional roadmap of human preimplantation development (Petropoulos et. al., Cell 2016). Subsequently the lab identified cell surface markers for naïve and primed pluripotent stem cells (Collier et. al., Cell Stem Cell 2017). Adult oogonial stem cells have been suggested to reside in the adult human ovary with a therapeutic potential to treat infertility. The laboratory have through two papers refuted such claims and through single cell sequencing mapped the cell types of the human ovarian cortex and established that the putative stem cells do not harbor the capacity to make oocytes and are instead mistaken perivascular cells (Zhang et. al., Nature Medicie 2015, Wagner et. al., Nature Communications 2020).

In order to use embryonic stem cells in reparative medicine the cells must be established and cultured under Good Manufacturing Practice (GMP). For this purpose the lab have a new cell line (KARO1) within the GMP manufacturing facility at Karolinska University Hospital. Another hurdle that needs to be addressed is the immunological barrier when transplanting allogeneic cells. For that reason the laboratory have explored the use of genome editing to evade the immune system by eliminating HLA presentation (Petrus-Reurer et. al., Stem Cell Reports 2020).

Finally, building on our established xeno-free and defined protocol to generate stem cell derived derived retinal cells (Plaza-Reyes et al 2016 Stem Cell Reports) we have identified cell surface markers for retinal pigmented epithelial cells and established a streamlined protocol for RPE differentiation (Petrus-Reurer et. al., Stem Cell Transl Med. 2020, Plaza Reyes et. al., Nature Communication 2020) which now puts us in the position to initiate clinical trial together with St Erik Eye Hospital to test our stem cell based treatment strategy of age-related macular degeneration.

Selected Publications

Collier, A. J., Panula, S. P., Schell, J. P., Chovanec, P., Plaza Reyes, A., Petropoulos, S., Corcoran, A. E., Walker, R., Douagi, I., Lanner, F., &Rugg-Gunn, P. J. (2017). Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States. Cell Stem Cell, 20(6), 874–890. https://doi.org/10.1016/j.stem.2017.02.014

Petropoulos, S., Edsgärd, D., Reinius, B., Deng, Q., Panula, S. P., Codeluppi, S., Plaza Reyes, A., Linnarsson, S., Sandberg, R., &Lanner, F. (2016). Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos. Cell, 165(4), 1012–1026. https://doi.org/10.1016/j.cell.2016.03.023

Petrus-Reurer, S., Kumar, P., Padrell Sánchez, S., Aronsson, M., André, H., Bartuma, H., Plaza Reyes, A., Nandrot, E. F., Kvanta, A., &Lanner, F. (2020). Preclinical safety studies of human embryonic stem cell-derived retinal pigment epithelial cells for the treatment of age-related macular degeneration. Stem Cells Translational Medicine, 9(8), 936–953. https://doi.org/10.1002/sctm.19-0396

Petrus-Reurer, S., Winblad, N., Kumar, P., Gorchs, L., Chrobok, M., Wagner, A. K., Bartuma, H., Lardner, E., Aronsson, M., Plaza Reyes, Á., André, H., Alici, E., Kaipe, H., Kvanta, A., &Lanner, F. (2020). Generation of Retinal Pigment Epithelial Cells Derived from Human Embryonic Stem Cells Lacking Human Leukocyte Antigen Class I and II. Stem Cell Reports, 14(4), 648–662. https://doi.org/10.1016/j.stemcr.2020.02.006

Plaza Reyes, A., Petrus-Reurer, S., Antonsson, L., Stenfelt, S., Bartuma, H., Panula, S., Mader, T., Douagi, I., André, H., Hovatta, O., Lanner, F., &Kvanta, A. (2016). Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model. Stem Cell Reports, 6(1), 9–17. https://doi.org/10.1016/j.stemcr.2015.11.008

Plaza Reyes, A., Petrus-Reurer, S., Padrell Sánchez, S., Kumar, P., Douagi, I., Bartuma, H., Aronsson, M., Westman, S., Lardner, E., André, H., Falk, A., Nandrot, E. F., Kvanta, A., &Lanner, F. (2020). Identification of cell surface markers and establishment of monolayer differentiation to retinal pigment epithelial cells. Nature Communications, 11, 1609. https://doi.org/10.1038/s41467-020-15326-5

Wagner, M., Yoshihara, M., Douagi, I., Damdimopoulos, A., Panula, S., Petropoulos, S., Lu, H., Pettersson, K., Palm, K., Katayama, S., Hovatta, O., Kere, J., Lanner, F., &Damdimopoulou, P. (2020). Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells. Nature Communications, 11(1), 1147. https://doi.org/10.1038/s41467-020-14936-3

Zhang, H., Panula, S., Petropoulos, S., Edsgärd, D., Busayavalasa, K., Liu, L., Li, X., Risal, S., Shen, Y., Shao, J., Liu, M., Li, S., Zhang, D., Zhang, X., Gerner, R. R., Sheikhi, M., Damdimopoulou, P., Sandberg, R., Douagi, I., …Liu, K. (2015). Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells. Nature Medicine, 21(10), 1116–1118. https://doi.org/10.1038/nm.3775