RESUMEN
Over the past decade, the induction protocols for the two types of kidney organoids (nephron organoids and ureteric bud organoids) from pluripotent stem cells (PSCs) have been established based on the knowledge gained in developmental nephrology. Kidney organoids are now used for disease modeling and drug screening, but they also have potential as tools for clinical transplantation therapy. One of the options to achieve this goal would be to assemble multiple renal progenitor cells (nephron progenitor, ureteric bud, stromal progenitor) to reproduce the organotypic kidney structure from PSCs. At least from mouse PSCs, all the three progenitors have been induced and assembled into such "higher order" kidney organoids. We will provide an overview of the developmental nephrology required for the induction of renal progenitors and discuss recent advances and remaining challenges of kidney organoids for clinical transplantation therapy.
RESUMEN
The kidney is an important organ for maintenance of homeostasis in the human body. As renal failure progresses, renal replacement therapy becomes necessary. However, there is a chronic shortage of kidney donors, creating a major problem for transplantation. To solve this problem, many strategies for the generation of transplantable kidneys are under investigation. Since the first reports describing that nephron progenitors could be induced from human induced pluripotent stem cells, kidney organoids have been attracting attention as tools for studying human kidney development and diseases. Because the kidney is formed through the interactions of multiple renal progenitors, current studies are investigating ways to combine these progenitors derived from human induced pluripotent stem cells for the generation of transplantable kidney organoids. Other bioengineering strategies, such as decellularization and recellularization of scaffolds, 3-dimensional bioprinting, interspecies blastocyst complementation and progenitor replacement, and xenotransplantation, also have the potential to generate whole kidneys, although each of these strategies has its own challenges. Combinations of these approaches will lead to the generation of bioengineered kidneys that are transplantable into humans.
Asunto(s)
Células Madre Pluripotentes Inducidas , Trasplante de Riñón , Humanos , Riñón , Bioingeniería , Nefronas , Trasplante de Riñón/efectos adversos , Andamios del TejidoRESUMEN
BACKGROUND: Peritoneal dialysis (PD) is essential for patients with end-stage renal disease. Peritoneal fibrosis (PF) is a complex inflammatory, fibrogenic process. No effective treatments are available to prevent these processes. Hepatocyte growth factor (HGF) possesses anti-inflammatory and anti-fibrotic properties. The aim of this study was to analyze whether HGF suppresses MGO-induced peritoneal inflammation and fibrosis in a mouse model. METHODS: PF was induced by intraperitoneal (IP) injections of MGO for 14 days. C57/BL/6 mice were divided into three groups: Sham group (only vehicle); Sham + MGO group (PF induced by MGO); and HGF + MGO group (PF mice treated with recombinant human-HGF). PF was assessed from tissue samples by Masson's trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry and quantitative real-time PCR. RESULTS: MGO-injected mice showed significant thickening of the submesothelial compact zone with PF. Treatment with HGF significantly reduced PM thickness and suppressed the expression of collagen I and III and α-SMA. Expression of profibrotic and proinflammatory cytokines (TGF-ß, TNF-α, IL-1ß) was reduced by HGF treatment. The number of macrophages, and M1 and M2 macrophage-related markers, such as CD86, CD206, and CD163, was reduced in HGF + MGO mice. CONCLUSION: HGF attenuates MGO-induced PF in mice. Furthermore, HGF treatment reduces myofibroblast and macrophage infiltration, and attenuates the upregulated expression of proinflammatory and profibrotic genes in peritoneal tissues. HGF might be an effective approach to prevent the development of PF in patients undergoing PD.