Transplantation of decellularized porcine kidney grafts repopulated with primary human cells demonstrates filtration function in pigs

Communications Medicine, Год журнала: 2024, Номер 4(1)

Опубликована: Дек. 5, 2024

End-stage renal disease is a growing global health issue, disproportionately impacting low- and middle-income countries. While kidney transplantation remains the best treatment for end-stage disease, access to this modality limited by chronic donor organ shortages. To address critical need, we are developing transplantable bioengineered grafts. Podocyte differentiation was achieved in adherent monoculture through Wnt TGF-β inhibition with IWR-1 SB431542, respectively. Podocytes along endothelial cells were then used recapitulate glomeruli within decellularized porcine scaffolds generate kidneys These grafts functionally assessed via normothermic perfusion which compared recellularized only as control bi-culture comprised of podocytes. Heterotopic implantation further tested graft function over 3 successive implant sessions 1–2 per session. We demonstrate ability source primary human podocytes at scale. Decellularized repopulated exhibit native glomerular structure display blood filtration capabilities during testing. Extending these findings clinically relevant model, produce urine indices when heterotopically implanted pigs. Our results showcase human-scale, capable performing requisite function. This study reinforces possibility bioengineering kidneys, could someday provide increased more equitable disease. issue while option, generated first removing all cellular material from pig followed delivery appropriate sites kidneys. show that our carry out essential functions being able filter urine. promising step toward development kidney, has future potential widespread Lo et al. into The have

Язык: Английский

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The ability of remaining glomerular podocytes to adapt to the loss of their neighbours decreases with age

Cell and Tissue Research, Год журнала: 2022, Номер 388(2), С. 439 - 451

Опубликована: Март 15, 2022

Progressive podocyte loss is a feature of healthy ageing. While previous studies have reported age-related changes in number, density and size associations with proteinuria glomerulosclerosis, few examined how the response remaining podocytes to depletion age. Mild was induced PodCreiDTR mice aged 1, 6, 12 18 months via intraperitoneal administration diphtheria toxin. Control received vehicle. Podometrics, glomerular pathology were assessed, together expression p-rp-S6, phosphorylation target that represents activity mammalian rapamycin (mTOR). Podocyte number per glomerulus did not change control 18-month time period examined. However, at had largest lowest density. 6 resulted mild albuminuria but no whereas similar levels both glomerulosclerosis. Following months, p-rp-S6 positive increased significantly, this associated an adaptive increase volume. age, unable further elevate mTOR or undergo hypertrophic adaptation depletion, resulting marked pathology. These findings demonstrate importance mTORC1-mediated hypertrophy physiological (ageing) settings, highlighting functional limit reached under conditions.

Язык: Английский

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Potential renal stem/progenitor cells identified by in vivo lineage tracing

AJP Renal Physiology, Год журнала: 2022, Номер 322(4), С. F379 - F391

Опубликована: Фев. 1, 2022

Mammalian kidneys consist of more than 30 different types cells. A challenging task is to identify and characterize the stem/progenitor subpopulations that establish lineage relationships among these cellular elements during nephrogenesis in embryonic neonate tissue homeostasis and/or injury repair mature kidney. Moreover, potential clinical utility cells holds promise for development new regenerative medicine approaches treatment renal diseases. Stem are defined by unlimited self-renewal capacity pluripotentiality. Progenitor have pluripotentiality but no or limited potential. Cre-LoxP-based vivo genetic tracing a powerful tool their native environment. Hypothetically, this technique enables investigators accurately track progeny single cell group The Cre/LoxP system has been widely used uncover function genes various mammalian tissues through analyses. In review, we summarize recent advances characterization Cre drivers use identifying both developing mouse kidneys.

Язык: Английский

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Novel therapeutic perspectives for crescentic glomerulonephritis through targeting parietal epithelial cell activation and proliferation

Expert Opinion on Therapeutic Targets, Год журнала: 2023, Номер 27(1), С. 55 - 69

Опубликована: Янв. 2, 2023

Introduction Kidney injury is clinically classified as crescentic glomerulonephritis (CrGN) when ≥50% of the glomeruli in a biopsy sample contain lesions. However, current strategies, such systemic immunosuppressive therapy and plasmapheresis for CrGN, are partially effective, these drugs have considerable side effects. Hence, targeted to prevent glomerular crescent formation expansion remains an unmet clinical need.Areas covered Hyperproliferative parietal epithelial cells (PECs) main constituent with cell-tracing evidence. Crescents obstruct flow primary urine, pressure capillaries, degenerate affected nephrons. We reviewed markers PEC activation proliferation, potential therapeutic effects thrombin receptor inhibitors, how podocytes cross-talk PECs. These experiments may help identify early specific targets prevention treatment injury.Expert opinion Inhibiting proliferation CrGN can alleviate progression, which has been supported by preclinical studies evidence genetic deletion. Clarifying outcome transformation podocyte phenotype suppressing thrombin, receptors, hyperproliferation strategies will be research goals next ten years.

Язык: Английский

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Aging-Related Functional and Structural Changes in Renal Tissues: Lesson from a Camel Model

Microscopy and Microanalysis, Год журнала: 2021, Номер 27(3), С. 566 - 578

Опубликована: Март 10, 2021

Abstract

Язык: Английский

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