Breakthrough Method Enhances Production of Kidney Progenitor Cells for Regenerative Medicine

A team of researchers from Kyoto University has made a significant advancement in the field of regenerative medicine by developing a novel method to cultivate induced pluripotent stem cell-derived kidney progenitor cells. This breakthrough promises to enhance the viability of renal regenerative therapies for patients suffering from kidney diseases.

The ongoing challenge in modern medicine lies in the limited treatment options available for acute kidney injury (AKI) and chronic kidney disease (CKD). Regenerative medicine, specifically through cell replacement therapies, presents a new avenue of hope for affected individuals. However, the large-scale production of the necessary progenitor cells has posed considerable difficulties until now.

In their study, the researchers utilized a mouse model of AKI to evaluate the therapeutic efficacy of human induced pluripotent stem cell-derived nephron progenitor cells (hiPSC-NPCs). Following transplantation of these cells into mice that had experienced kidney damage due to the chemotherapy drug cisplatin, a marked improvement in the animals' survival rates was observed. The transplantation effectively mitigated the decline in kidney function, highlighting the potential of hiPSC-NPCs in treating renal injuries.

Considering the substantial size difference between mice and humans, the researchers recognized that an extensive quantity of these cells would be necessary for potential therapeutic applications in human patients. This realization prompted them to explore innovative methods for expanding hiPSC-NPCs in vitro.

Rather than adhering to traditional single-layer culturing techniques, the team opted to cultivate the cells in clusters within a suspension medium that included three specific chemicals known to support kidney growth and development. This new approach allowed the cells to maintain their characteristic protein markers and continue expanding efficiently. When these clusters were transplanted into the kidneys of mice, they successfully differentiated into various kidney cell types, contributing to the formation of essential organ structures.

The researchers also discovered that the growth of these cell aggregates was heavily influenced by the initial cell density, indicating that the availability of oxygen might be a limiting factor in the expansion process. Notably, the cells expanded using this method exhibited comparable therapeutic potential as those generated through traditional means when implanted in mouse models of AKI and CKD, suggesting that this technique could be crucial for mass-producing functional cells for regenerative therapies.

Furthermore, the research team conducted comprehensive gene expression analyses, identifying a novel marker that could facilitate the purification of hiPSC-NPCs. Utilizing this marker, they demonstrated the ability to expand the progenitor cells by a factor of 100 over just two passages, significantly enhancing their viability for future applications.

Additionally, the study revealed that hiPSC-NPCs produce vascular endothelial growth factor A (VEGF-A), a protein known for its role in promoting blood vessel formation and maintenance. The absence of the VEGFA gene in these cells resulted in reduced therapeutic effectiveness when transplanted, underscoring the importance of this factor in their functionality.

This research marks a pivotal step toward the potential application of hiPSC-NPCs in treating AKI and CKD, providing a much-needed method for their large-scale production outside the human body. The identification of a new purification marker and the elucidation of underlying mechanisms that contribute to the therapeutic benefits of these cells offer promising prospects for the future of renal regenerative medicine.