Development of novel strategies to regenerate the human kidney

Leuning, D.G. (2018)

Doctoral Thesis

Within this thesis several novel strategies to regenerate the human kidney are exploited. The first strategy is to improve kidney function is by mesenchymal stromal cell (MSC) therapy. In chapter 2 the current status of clinical trials with MSC therapy are discussed. In chapter 3 we show an extensive characterization of MSCs derived from human kidney (hkPSCs) compared to bone marrow derived MSCs (bmMSCs) and show that hkPSCs show organotypic expression signatures and functionality. For fluent clinical translation, we developed a clinical grade acceptable standard operation procedure (SOP) (chapter 4). In chapter 5 we show that the cytokine secretion profile of both hkPSCs and bmMSCs was closely related to cell morphology adaptation to culture surface topography and was stromal cell type specific. In chapter 6 we show that not only the kidney cortex but also the kidney capsule contains a stromal cell population. In chapter 7 we report the regeneration of kidney vasculature by repopulating the vascular compartment of human and rat kidney matrices with hiPSC-derived endothelial cells. We show efficient cell delivery, adherence and survival of these endothelial cells as a first, but critical, step towards a human bioengineered kidney.

• Kidney regeneration
• Kidney transplantation
• Regenerative medicine
• Stem cell therapy
• Kidney bioengineering

• All authors: Leuning, D.G.
• Supervisor: Rabelink, A.J.; Kooten, C. van
• Co-supervisor: Engelse, M.A.
• Committee: Atsma, D.E.; Passier, P.C.J.J.; Hoogduijn, M.J.; Romagnani, P.; Fibbe, W.E.
• Qualification: Doctor (dr.)
• Awarding Institution: Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2018-07-03
• ISBN (print): 9789462959712
• Sponsorship: Nierstichting Alrijne Zorggroep Nederlandse Transplantatie Vereniging