From Infancy to Fancy: A Glimpse into the Evolutionary Journey of Podocytes in Culture

Abstract

Podocytes are critical components of the filtration barrier and responsible for maintaining healthy kidney function. An assault on podocytes is generally associated with progression of chronic glomerular diseases. Therefore, podocyte pathophysiology is a favorite subject of research for nephrologists. Despite this, podocyte research has lagged behind because of the unavailability of techniques for culturing such specialized cells ex vivo in quantities that are adequate for mechanistic studies. In recent years, this problem was circumvented by the efforts of researchers who successfully developed several in vitro podocyte cell culture model systems that paved the way for incredible discoveries in the field of nephrology. This review embarks us on a journey that provides a comprehensive insight into the groundbreaking breakthroughs and novel technological advances made in the field of podocyte cell culture so far, beginning from its inception, evolution, and progression. Herein, we also describe in detail the pros and cons of different models that are currently being used to culture podocytes. Our extensive and exhaustive deliberation on the status of podocyte cell culture will facilitate the researchers to wisely choose an appropriate model for their own research to avoid potential pitfalls in the future.

Using Drosophila Nephrocytes to Understand the Formation and Maintenance of the Podocyte Slit Diaphragm

“…However, each system came with its own strengths and limitations. For example, the in vitro system provides ready access to podocytes, but their key characteristics are often rapidly lost under cell culture conditions ( Agarwal et al, 2020 ). On the other hand, while the in vivo system studies podocytes in their physiological environment, the cells have been notoriously difficult to access for in vivo imaging ( Siegerist et al, 2018 ).…”

Glomerulus-on-a-Chip: Current Insights and Future Potential Towards Recapitulating Selectively Permeable Filtration Systems

“…However, the immortalized podocytes are generally not recognized as a valid cell source owing to the loss of maturation markers such as the slit diaphragm proteins, even at culture conditions around 37°C where the proliferation is expected to be inhibited, and the differentiation to be induced. 84 , 85 …”

“…However, not only are the sources of primary podocytes limited ethically but also their mitotic potential is negligible. In addition, there is an inevitable loss of the maturation markers during the cryopreservation and passaging; 85 hence, they are unlikely to be a useful source. Here, the development of a culture technique induces lineage-specific cells, including glomeruli in kidney orgaonid 25–30 or podocytes 42 , 43 , 86–89 from human induced pluripotent stem (hiPS) cells, which is a breakthrough in the last decade concerning the problem of cell sources.…”

“… 41 This method is reasonable considering podocytes generally lose their maturation markers during outgrowth from isolated glomeruli. 85 …”

“… 87 Although most of the problems with the podocyte cell sources are due to incompatibility between the podocyte maturation and cell number, this induction technique can solve this problem. 85 …”