Magdalena Lorenowicz,
Head of the Advanced In Vitro Model Systems Department,
Biomedical Primate Research Center
Magdalena Lorenowicz studied Biotechnology at the Jagiellonian University in Kraków. In September 2001 she moved to Amsterdam to start her Ph.D. research. During her Ph.D. studies she investigated the role of cAMP signalling in the regulation of leukocyte chemotaxis and endothelial barrier function. After completion of her thesis, Magdalena moved to the Hubrecht Institute in Utrecht, where supported by prestigious VENI award (2008) she focused on the mechanism of Wnt secretion, combining the genetics of C. elegans with cutting edge cell biology techniques in mammalian cells. In April 2012 she joined the Department of Cell Biology and Center for Molecular Medicine at University Medical Center Utrecht to set up her own research line investigating molecular mechanisms regulating the immunosuppressive and regenerative properties of the human mesenchymal stem stromal cells (MSC) with the ultimate goal to directly link her expertise in studying cell-cell communication with clinical applications. In 2015 she moved to Regenerative Medicine Center Utrecht, where she became a principal investigator, expanded her research group and worked on the interphase of fundamental research and regenerative medicine. In November 2022 she moved to the Biomedical Primates Research Center, where she is a head of the Advanced In vitro Models Systems (AIMS) department and continues to investigate biology of MSC and their in vivo function in context of different tissues with the final goal to improve MSC-based therapies.
Mesenchymal Stromal-Stem Cells Promote Intestinal Epithelium Regeneration after Chemotherapy-Induced Damage
Tuesday, 20 June 2023 at 11:00
Add to Calendar ▼2023-06-20 11:00:002023-06-20 12:00:00Europe/LondonMesenchymal Stromal-Stem Cells Promote Intestinal Epithelium Regeneration after Chemotherapy-Induced DamageOrganoids and Spheroids Europe 2023 in Rotterdam, The NetherlandsRotterdam, The NetherlandsSELECTBIOenquiries@selectbiosciences.com
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for leukemia and a range of non-malignant congenital disorders. An essential component of HSCT is the conditioning regimen, consisting of chemotherapy and/or total body irradiation, administrated prior to hematopoietic cell infusion. The success of the therapy is hampered by the development of acute graft-versus-host-disease (aGvHD), in which immune cells from the donor attack healthy recipient tissue, including the liver, skin, and gut. Especially intestinal aGvHD is a life threatening complication. Data from our institution and others demonstrate rescue of ~50% of patients suffering from aGvHD with mesenchymal stromal cells (MSCs) in Phase II clinical trials. However, the underlying mechanism of MSCs contributing to steroid-resistant aGvHD treatment is still unknown. Current models in animal studies and homogeneous cell lines are highly relevant to the field, but these approaches are limited because of the high complexity of human tissues and organs. Immortalized and human primary cell lines have enabled detailed investigation of specific cell types, but do not recapitulate the cellular heterogeneity characteristics for physiological tissues. For this purpose, a suitable in vitro model is needed, which partially recapitulates the in vivo situation of GvHD patients and allows to study the mode of action of MSCs during organ/tissue regeneration in these patients. Here we developed a novel co-culture model of chemotherapy-induced small intestine damaged organoids, self-organizing 3D mini-guts derived from human stem cells, and MSCs and studied the regenerative aspects of MSC treatment on damaged intestinal epithelium by transcriptomic and proteomic analysis. Our study shows that busulfan, the chemotherapeutic commonly used as conditioning regimen before HSCT, damaged the small intestine epithelium by affecting pathways regulating epithelial mesenchymal transition, proliferation, and apoptosis. The MSCs reversed these effects by regulating genes and proteins involved in these pathways, which we also confirmed by functional evaluation of proliferation and apoptosis. Collectively, we demonstrate that our novel in vitro co-culture model is a new valuable tool to mimic the in vivo interplay between damaged intestinal epithelium and MSCs, providing a micro-physiological environment relevant to that of GvHD, and allows to study the molecular mechanism behind the therapeutic effects of MSCs in these patients.
Add to Calendar ▼2023-06-19 00:00:002023-06-20 00:00:00Europe/LondonOrganoids and Spheroids Europe 2023Organoids and Spheroids Europe 2023 in Rotterdam, The NetherlandsRotterdam, The NetherlandsSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2023-06-20 11:00:002023-06-20 12:00:00Europe/LondonMesenchymal Stromal-Stem Cells Promote Intestinal Epithelium Regeneration after Chemotherapy-Induced DamageOrganoids and Spheroids Europe 2023 in Rotterdam, The NetherlandsRotterdam, The NetherlandsSELECTBIOenquiries@selectbiosciences.com
