Have we hit a wall with whole kidney decellularization and recellularization: A review

Haan, Marlon J.A. de; Witjas, Franca M.R.; Engelse, Marten A.; Rabelink, Ton J.

doi:10.1016/j.cobme.2021.100335

Cited by 12 publications

(12 citation statements)

References 63 publications

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“…Additional efforts have also reported the successful differentiation of embryonic and induced pluripotent stem cells into tubular, glomerular, and whole nephron organoids [60][61][62][63][64][65][66][67]. A greater understanding of the roles of key signaling pathways has also allowed investigators to differentiate stem cell niches into various lineages.…”

Section: Cell and Organoid Transplantationmentioning

confidence: 99%

Still Finding Ways to Augment the Existing Management of Acute and Chronic Kidney Diseases with Targeted Gene and Cell Therapies: Opportunities and Hurdles

Corridon¹

2023

Preprint

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The rising global incidence of acute and chronic kidney diseases has increased the demand for renal replacement therapy. This issue, compounded with the limited availability of viable kidneys for transplantation, has propelled the search for alternative strategies to address the growing health and economic burdens associated with these conditions. In the search for such alternatives, significant efforts have been devised to augment the current and primarily supportive management of renal injury with novel regenerative strategies. For example, gene- and cell-based approaches that utilize recombinant peptides/proteins, gene, cell, organoid, and RNAi technologies have shown promising outcomes primarily in experimental models. Supporting research has also been conducted to improve our understanding of the critical aspects that facilitate the development of efficient gene- and cell-based techniques that the complex structure of the kidney has traditionally limited. This manuscript is intended to communicate efforts that have driven the development of such therapies by identifying the vectors and delivery routes needed to drive exogenous transgene incorporation that may support the treatment of acute and chronic kidney diseases.

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Section: Cell and Organoid Transplantationmentioning

confidence: 99%

Still Finding Ways to Augment the Existing Management of Acute and Chronic Kidney Diseases with Targeted Gene and Cell Therapies: Opportunities and Hurdles

Corridon¹

2023

Preprint

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“…This includes whole organ decellularization using different types of protocols. 111 Critical issues during the process of decellularizing human-sized kidneys from pigs but also human kidneys are to effectively remove all cellular components including cell surface receptors and DNA to avoid immunological rejection, and to maintain the architecture of extracellular matrix components and vasculature after this treatment to permit effective recellularization. 112,113 It should be mentioned that the abundance of discarded human kidneys not useful for transplantation has also spurred attempts to use them as scaffolds for recellularization.…”

Section: Brief Survey On Alternative Approaches To Solve the Problem ...mentioning

confidence: 99%

Wearable and implantable artificial kidney devices for end‐stage kidney disease treatment: Current status and review

et al. 2022

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Background: Chronic kidney disease (CKD) is a major cause of early death worldwide. By 2030, 14.5 million people will have end-stage kidney disease (ESKD, or CKD stage 5), yet only 5.4 million will receive kidney replacement therapy (KRT) due to economic, social, and political factors. Even for those who are offered KRT by various means of dialysis, the life expectancy remains far too low.Observation: Researchers from different fields of artificial organs collaborate to overcome the challenges of creating products such as Wearable and/or Implantable Artificial Kidneys capable of providing long-term effective physiologic kidney functions such as removal of uremic toxins, electrolyte homeostasis, and fluid regulation. A focus should be to develop easily accessible, safe, and inexpensive KRT options that enable a good quality of life and will also be available for patients in less-developed regions of the world.Conclusions: Hence, it is required to discuss some of the limits and burdens of transplantation and different techniques of dialysis, including those performed at home. Furthermore, hurdles must be considered and overcome to develop wearable and implantable artificial kidney devices that can help to improve the quality of life and life expectancy of patients with CKD.

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“…Specifically, it is difficult to remove all cellular components within a whole organ; thus, decellularization thresholds have been proposed to define critical limits for decellularization 28 . Conversely, adequate repopulation of the epithelial compartment still needs to be attainable 29 , particularly in complex organs like the kidney. Current recellularization methods are also plagued by events that lead to incomplete reendothelialization, resulting in structural and functional vulnerabilities.…”

Section: Introductionmentioning

confidence: 99%

Capturing effects of blood flow on the transplanted decellularized nephron with intravital microscopy

Corridon

2023

Sci Rep

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Organ decellularization creates cell-free, collagen-based extracellular matrices that can be used as scaffolds for tissue engineering applications. This technique has recently gained much attention, yet adequate scaffold repopulation and implantation remain a challenge. Specifically, there still needs to be a greater understanding of scaffold responses post-transplantation and ways we can improve scaffold durability to withstand the in vivo environment. Recent studies have outlined vascular events that limit organ decellularization/recellularization scaffold viability for long-term transplantation. However, these insights have relied on in vitro/in vivo approaches that need enhanced spatial and temporal resolutions to investigate such issues at the microvascular level. This study uses intravital microscopy to gain instant feedback on their structure, function, and deformation dynamics. Thus, the objective of this study was to capture the effects of in vivo blood flow on the decellularized glomerulus, peritubular capillaries, and tubules after autologous and allogeneic orthotopic transplantation into rats. Large molecular weight dextran molecules labeled the vasculature. They revealed substantial degrees of translocation from glomerular and peritubular capillary tracks to the decellularized tubular epithelium and lumen as early as 12 h after transplantation, providing real-time evidence of the increases in microvascular permeability. Macromolecular extravasation persisted for a week, during which the decellularized microarchitecture was significantly and comparably compromised and thrombosed in both autologous and allogeneic approaches. These results indicate that in vivo multiphoton microscopy is a powerful approach for studying scaffold viability and identifying ways to promote scaffold longevity and vasculogenesis in bioartificial organs.

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Have we hit a wall with whole kidney decellularization and recellularization: A review

Cited by 12 publications

References 63 publications

Still Finding Ways to Augment the Existing Management of Acute and Chronic Kidney Diseases with Targeted Gene and Cell Therapies: Opportunities and Hurdles

Still Finding Ways to Augment the Existing Management of Acute and Chronic Kidney Diseases with Targeted Gene and Cell Therapies: Opportunities and Hurdles

Wearable and implantable artificial kidney devices for end‐stage kidney disease treatment: Current status and review

Capturing effects of blood flow on the transplanted decellularized nephron with intravital microscopy

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