Nephron generation in kidney cortices through injection of pretreated mesenchymal stem cell-differentiated tubular epithelial cells. 2019

Toshihiko Machiguchi, and Tatsuo Nakamura
Laboratory of Organ and Tissue Reconstruction, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Electronic address: machiguchi.toshihiko.23u@st.kyoto-u.ac.jp.

Transplantation of artificially treated metanephroi or pluripotent stem cell-injected blastocyst-derived whole kidneys will be established in the near future as a useful therapeutic method for renal failure. We have attempted in vivo nephron generation for kidney repair by exploiting cellular interactions via conditioned media (CMs). In a previous report, we showed stimulative cross-talks between vascular endothelial cells (VECs) and tubular epithelial cells (TECs) on cell proliferation and morphological changes, the differentiation of mesenchymal stem cells (MSCs) into TECs by TEC-CM, and nephron generation from TECs or MSCs in rat subcutaneous spaces. In this study adding collecting duct cells (CDCs) and their CM, we demonstrate the suppressive actions of CDC-CM against VECs and TECs, in addition to stimulative cross-talks between VECs and TECs, during the above changes. Furthermore, CDC-CM, similar to TEC-CM, caused differentiation of MSCs into TECs. Thus, we injected CDC-CM-induced MSC-differentiated TECs into rat kidney cortices. The pretreatment of cells in 3-dimensional culture using a small amount of gel complex before implantation triggered the generation of much more nephron-like structures, compared to the implantation of non-pretreated cells. Our method of injecting pretreated TECs into kidney cortices might have applications for repairing dysfunctional kidney tissue.

UI MeSH Term Description Entries
D007267 Injections Introduction of substances into the body using a needle and syringe. Injectables,Injectable,Injection
D007672 Kidney Cortex The outer zone of the KIDNEY, beneath the capsule, consisting of KIDNEY GLOMERULUS; KIDNEY TUBULES, DISTAL; and KIDNEY TUBULES, PROXIMAL. Cortex, Kidney
D007684 Kidney Tubules Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER. Kidney Tubule,Tubule, Kidney,Tubules, Kidney
D007685 Kidney Tubules, Collecting Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of Bellini) which opens on the summit of the papilla. Kidney Collecting Ducts,Kidney Collecting Duct,Collecting Duct, Kidney,Collecting Ducts, Kidney
D002450 Cell Communication Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017077 Culture Media, Conditioned Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis). Conditioned Culture Media,Conditioned Culture Medium,Conditioned Media,Conditioned Medium,Culture Medium, Conditioned,Media, Conditioned,Medium, Conditioned

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