New aspects of podocyte cell biology

P Mundel, J Reiser - Kidney and Blood Pressure Research, 1997 - karger.com
P Mundel, J Reiser
Kidney and Blood Pressure Research, 1997karger.com
Podocytes are of great relevance for the physiology of the glomerulus [1]. Loss of podocytes
under pathological conditions finally leads to end-stage renal disease (ESRD)[2]. The
analysis of podocytes under normal and pathological conditions has been difficult because
no in vitro model has been available that could reproduce the decisive steps of podocyte
differentiation leading to process formation. Therefore, a cell culture system that permits the
detailed cell and molecular biological analysis of podocyte differentiation represents a major …
Podocytes are of great relevance for the physiology of the glomerulus [1]. Loss of podocytes under pathological conditions finally leads to end-stage renal disease (ESRD)[2]. The analysis of podocytes under normal and pathological conditions has been difficult because no in vitro model has been available that could reproduce the decisive steps of podocyte differentiation leading to process formation. Therefore, a cell culture system that permits the detailed cell and molecular biological analysis of podocyte differentiation represents a major step towards understanding these highly specialized cells. Cultivation of podocytes is difficult and represented for years an unsolved problem. There has been an ongoing debate regarding the relevance of cultured podocytes [3-5]. Working with cultured podocytes was associated with two major problems. First, podocytes had to be clearly separated from outgrowing parietal epithelial cells of Bowman’s capsule. Second, the rapid loss of differentiation seen in cultured podocytes had to be overcome. This dedifferentiation in vitro is reflected by the reexpression of lymphohematopoet-ic marker antigens [6]‚which in vivo are only transiently expressed in podocytes during the early stages of renal or-ganogenesis [7]. Most important, this dedifferentiation leads to the loss of the developed cytoarchitecture and of synaptopodin, a marker of a differentiated podocyte pheno-type. In vivo, the expression of synaptopodin is associated with the formation and presence of podocyte processes [8]. Taking advantage of a novel cell culture approach, we not only demonstrated clearly the cellular identity of cultured podocytes, but also induced a degree of differentiation that comes close to that of podocytes in the kidney [9]. Based on these improved culture techniques, conditionally immortalized podocyte cell lines were established, which can not only be induced to differentiate but are also available in large amounts and constant quality [P. Mundel et al., submitted]. The literature describes several cell culture models for podocytes [1, 10]. However, with a few exceptions, all these cells grow as undifferentiated cobblestone cells. More recently, Yaoita et al.[11] reported the outgrowth of two cell types from isolated rat kidney glomeruli: a cobblestone phe-notype and an arborized-cell phenotype, which had previously been described in porcine glomerular cultures [12]. As only the arborized cells expressed synaptopodin (at that time termed pp44), these investigators concluded that only arboriozed cells are of podocyte origin, whereas cobblestones are derived from parietal cells of Bowman’s capsule. Our own data confirm the origin of arborized cells from podocytes, but do not support the parietal epithelial origin of cobblestones [9; P. Mundel et al., submitted].
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