Eddie Wisse
University of Maastricht, The Netherlands, M4I Division of Nanoscopy1 and Department of Internal Medicine2
Eddie Wissewas born in The Hague, The Netherlands and studied biology at Leiden University. In 1963 he joined the Laboratory for Electron Microscopy (Medical School) where he started the study of sinusoidal cells. Endothelial fenestrae, the distinction between endothelial and Kupffer cells and the new pit cells were the result of applying perfusion fixation to rat liver. After his PhD he became full professor at the Laboratory for Cell Biology and Histology at the University of Brussels (VUB), Belgium. The team published over 25 papers on sinusoidal cells in Hepatology and more in other journals. He organized three Kupffer Cell Symposia and produced 10 Proceedings (4.900 pages). After retirement he works at Maastricht University, Nanoscopy Division. The present focus is on the ultrastructure of sinusoidal cells in NASH and fibrosis in needle and wedge biopsies of intact human liver, fixed by new methods preserving the sinusoids and their cells.
Eddie Wisse1, Pauline Verhaegh2, Peter Peters1 and Ger Koek2University of Maastricht, The Netherlands, M4I Division of Nanoscopy1 and Department of Internal Medicine2In the sixties, an interest in hepatic sinusoidal cells... [ view full abstract ]
Eddie Wisse1, Pauline Verhaegh2, Peter Peters1 and Ger Koek2
University of Maastricht, The Netherlands, M4I Division of Nanoscopy1 and Department of Internal Medicine2
In the sixties, an interest in hepatic sinusoidal cells developed in several research institutes in The Netherlands. By EM, four types of sinusoidal cells were distinguished in rat liver: endothelial, Kupffer, fat-storing and pit cells. New methods for the isolation of sinusoidal cells enabled biochemical analysis. Soon, more researchers joined and cooperation resulted in projects, grants, working groups and inspiring meetings. Encouraged by this result, we organized the first International Kupffer Cell Symposium in Noordwijkerhout in 1977. After the second symposium (’82) a series of biannual international symposia followed. The early meetings were organized by Dick Knook and one of us (EW), later our new colleagues Kirn, Decker, McCuskey, Wake, Balabaud, Fraser, Arthur, Vidal Vanaclocha, Naito and Smedsrod joined the scientific committee and organized symposia themselves. We also produced a Kupffer Cell Bulletin and ten printed proceedings with a total of 4,900 pages. We sold these volumes, providing some money to cover the costs, no yearly membership fee was needed. ISHSR was created during the meeting in Tromsø. For a complete history see https://ishsr.net/index.php/ab... present EM work focusses on human sinusoidal cells in intact liver. There is general agreement that different agents cause liver injury, inducing inflammation, followed by fibrosis and cancer. Activation of stellate cells and formation of capillaries are thought to play an important role. We developed new methods for a perfusion-type of fixation of human liver wedge and needle biopsies, preserving the ultrastructure of sinusoids and their cells. Our observations in steatotic, NASH and fibrotic livers (grade 1 – 4) are as follows:
- there is no ultrastructural damage of parenchymal, endothelial, Kupffer and other cells
- apoptosis is absent, (single cell) necrosis is rare
- liver lobules, even in cirrosis, contain sinusoids and endothelial cells with fenestrae
- continuous capillaries or capillaries with diaphragmed fenestrae are very rare
- the number of fat droplets in stellate cells diminishes during progressing fibrosis
- connective tissue contains large numbers of fibroblasts, which can also be found in the space of Disse
- steatosis is diminished in later steps of fibrosis
- the EM-profile of myofibroblasts is unclear
Conclusion: in these diseased livers, all cells display healthy, intact ultrastructure. Fibroblasts are numerous within the connective tissue around the portal vein, in septa and sometimes around the sinusoids. Fibroblasts seem to be responsible for the deposition of collagen. Sinusoids are intact and are not transformed into or replaced by other types of capillaries. The healthy ultrastructure of all cells suggests that the liver is ready to regenerate when the invisible injuring factor is removed.
