Flow‐controlled fluoroscopic angiography for the assessment of vascular integrity in bioengineered kidneys

Abstract

Perfusion decellularization has been proposed as a promising method for generating nonimmunogenic organs from allogeneic or xenogeneic donors. Several imaging modalities have been used to assess vascular integrity in bioengineered organs with no consistency in the methodology used. Here, we studied the use of fluoroscopic angiography performed under controlled flow conditions for vascular integrity assessment in bioengineered kidneys. Porcine kidneys underwent ex vivo angiography before and after perfusion decellularization. Arterial and venous patencies were defined as visualization of contrast medium (CM) in distal capillaries and renal vein, respectively. Changes in vascular permeability were visualized and quantified. No differences in patency were detected in decellularized kidneys compared with native kidneys. However, focal parenchymal opacities and significant delay in CM clearance were detected in decellularized kidneys, indicating increased permeability. Biopsy‐induced leakage was visualized in both groups, with digital subtraction angiography revealing minimal CM leakage earlier than nonsubtracted fluoroscopy. In summary, quantitative assessment of vascular permeability should be coupled with patency when studying the effect of perfusion decellularization on kidney vasculature. Flow‐controlled angiography should be considered as the method of choice for vascular assessment in bioengineered kidneys. Adopting this methodology for organs premodified ex vivo under normothermic machine perfusion settings is also suggested.

Generation of vascular chimerism within donor organs

“…We used fluoroscopic angiography to visualize the isolated organs in situ. We recently suggested that this imaging modality should be routinely used for assessing vascular integrity in bioengineered organs 24 . Successful isolated perfusion was confirmed by fluoroscopic angiography (Fig.…”

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

“…Current studies have outlined vascular events that limit whole organ decellularization and recellularization techniques for long-term transplantation. Several microscopic and macroscopic approaches have examined the whole kidney scaffold structure and function in various settings [18][19][20][21][22][23][24][25][26]. Such investigations have proved that the decellularization process successfully removes remnant native cellular/tissue components and decellularizing agents while maintaining the vascular and ECM architectures in various large and small animal models.…”

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

“…Current studies have outlined vascular events that limit whole organ decellularization/recellularization techniques for long-term transplantation. Several microscopic and macroscopic approaches have been employed to examine whole kidney scaffold structure and function in various settings (Nakayama et al, 2010;Bonandrini et al, 2014;Sambi et al, 2017;Zambon et al, 2018;Cohen et al, 2020;Sabetkish et al, 2020;Cohen et al, 2021;Corridon, 2021;Pantic et al, 2022). Such investigations have provided evidence that the decellularization process successfully removes remnant native cellular/tissue components and decellularizing agents while maintaining the vascular and ECM architectures in various large and small animal models.…”