Research Project Description:

Chronic kidney disease affects 5-7 % of the population worldwide, and its incidence is increasing at an alarming rate. It is characterized by progressive loss of kidney function and defects in glomerular filtration, which can lead to end-stage renal disease. The loss of podocytes, highly specialized cells unable to regenerate, play a key role in the decline of GFR that leads to CKD. Therefore, there is an urgent need to develop new therapeutic approaches to stop cell death and replace lost podocytes in the mature kidney. Human induced pluripotent stem cells (hiPSCs) are an important tool for studying disease mechanisms and developing strategies for regenerating damaged podocytes. We, and others, have successfully differentiated hiPSCs into nephron progenitors and podocytes, but using these methods to create models of human disease in a “dish” has not been explored yet. This is because the current protocols to differentiate hiPSCs are not very efficient or reproducible. Thus, the aims of this proposal are; first, to generate reporter cell lines to optimize the differentiation of podocytes from hiPSCs and, second, to use this protocol to compare podocytes from mutant and control hiPSCs generated from Alport disease (AD) patients. Specifically, we set out to study AD because it is a common genetic disorder in Cyprus with variable clinical characteristics that often leads to CKD/ESRD, and there is a need to create human models of the disease. Overall, the project will help to develop more efficient differentiation protocols to generate podocytes, and to reveal new therapeutic targets for treating AD, paving the way for developing new cell therapies for CKD. Moreover, the use of cutting-edge technologies, such as hiPSCs cultures and CRISPR/Cas9 genome engineering will establish the field of Stem Cells and Regenerative Medicine in Cyprus. Apart from advancing biomedical research, this innovative project could also have a significant impact on society and stimulate the biotechnology and pharmaceutical industries.

Principal Investigator(s) and Coordinating Institution(s):

  • Prof Christodoulos Xinaris, University of Nicosia Medical School, Cyprus

Researchers at University of Nicosia Medical School:

  • Prof Christodoulos Xinaris
  • Dr Ricardo Romero
  • Prof Adonis Ioannides

UNIC Participating Institution:

  • University of Nicosia

Other Participating Institution(s):

  • Cyprus (The Cyprus Institute of Neurology and Genetics – CING)
  • Italy (Mario Negri Institute for Pharmacological Research – MNI)

Research Project Acronym: HUSMAD

Funding Agency: Research and Innovation Foundation (RIF)

Funding Programme: DIDAKTOR

Total Research Project Budget: €159,808

Research Project Status: Completed

Start and End Dates: 19 June 2019 – 20 December 2021

Funding Programme or Research Project Logo:

Related Links:

Related Publications:

  1. Romero-Guevara R., Ioannides A. & Xinaris C. (2020). Kidney Organoids as Disease Models: Strengths, Weaknesses and Perspectives. Frontiers in Physiology, 11: Art. Num. 563981 doi: 10.3389/fphys.2020.563981
  2. Romero-Guevara R., Nicolaou O., Petracca B., […] Ioannides A. & Xinaris C. (2023). Patient-derived podocyte spheroids reveal new insights into the etiopathogenesis of Alport syndrome. Frontiers in Cell and Developmental Biology, 11: Art. Num. 1111424

* Related Conference Participations:

  1. Romero-Guevara R. Presentation for the Pharmacology Course. Universidad de Ixtlahuaca, Mexico, 2020
  2. Presentation for UNIC Medical School, 2021
  3. The coordinator has given a lecture in Annual Meeting of Asia-Pacific Association of Medicine and Bio-Immunology and participated in the Expert Panel for Precision Medicine in Shenzhen (China, 2020) where the project was mentioned.