In Vivo Vascularization Chamber for the Implantation of Embryonic Kidneys.

A major obstacle to the implantation of ex vivo engineered tissues is the incorporation of functional vascular supply to support the growth of new tissue and to minimize ischemic injury. Existing prevascularization systems, such as arteriovenous (AV) loop-based systems, require microsurgery, limiting their use to larger animals. We aimed to develop an implantable device that can be prevascularized to enable vascularization of tissues in small rodents, and test its application on the vascularization of embryonic kidneys. Implanting the chamber between the abdominal aorta and the inferior vena cava, we detected endothelial cells and vascular networks after 48 h of implantation. Loading the chamber with collagen I (C), Matrigel (M), or Matrigel + vascular endothelial growth factor) (MV) had a strong influence on vascularization speed: Chambers loaded with C took 7 days to vascularize, 4 days for chambers with M, and 2 days for chambers with MV. Implantation of E12.5 mouse embryonic kidneys into prevascularized chambers (C, MV) was followed with significant growth and ureteric branching over 22 days. In contrast, the growth of kidneys in non-prevascularized chambers was stunted. We concluded that our prevascularized chamber is a valuable tool for vascularizing implanted tissues and tissue-engineered constructs. Further optimization will be necessary to control the directional growth of vascular endothelial cells within the chamber and the vascularization grade. Impact Statement Vascularization of engineered tissue, or organoids, constructs is a major hurdle in tissue engineering. Failure of vascularization is associated with prolonged ischemia time and potential tissue damage due to hypoxic effects. The method presented, demonstrates the use of a novel chamber that allows rapid vascularization of native and engineered tissues. We hope that this technology helps to stimulate research in the field of tissue vascularization and enables researchers to generate larger engineered vascularized tissues.

Bioprinting Scaffolds for Vascular Tissues and Tissue Vascularization.

In recent years, tissue engineering has achieved significant advancements towards the repair of damaged tissues. Until this day, the vascularization of engineered tissues remains a challenge to the development of large-scale artificial tissue. Recent breakthroughs in biomaterials and three-dimensional (3D) printing have made it possible to manipulate two or more biomaterials with complementary mechanical and/or biological properties to create hybrid scaffolds that imitate natural tissues. Hydrogels have become essential biomaterials due to their tissue-like physical properties and their ability to include living cells and/or biological molecules. Furthermore, 3D printing, such as dispensing-based bioprinting, has progressed to the point where it can now be utilized to construct hybrid scaffolds with intricate structures. Current bioprinting approaches are still challenged by the need for the necessary biomimetic nano-resolution in combination with bioactive spatiotemporal signals. Moreover, the intricacies of multi-material bioprinting and hydrogel synthesis also pose a challenge to the construction of hybrid scaffolds. This manuscript presents a brief review of scaffold bioprinting to create vascularized tissues, covering the key features of vascular systems, scaffold-based bioprinting methods, and the materials and cell sources used. We will also present examples and discuss current limitations and potential future directions of the technology.

Contribution of stem cells to kidney repair.

A current explanation for development of chronic renal injury is the imbalance between injurious mechanism and regenerative repair. The possibility that stem cells contribute to the repair of glomerular and tubular damage is of great interest for basic and translational research. Endogenous bone marrow-derived stem cells have been implicated in the repair of renal tissue, although the lineage of stem cells recruited has not been determined. If endogenous bone marrow-derived stem cells repopulate injured nephrons directly or act indirectly over a paracrine/endocrine mechanism remains also controversial. Therapeutic administration of exogenous bone marrow derived stem cells in animal models of acute renal injury suggests that a stem cell-based therapy may improve the recovery of both glomerular and tubular compartments. Whereas the therapeutic benefit of sorted hematopoietic stem cells remains uncertain, several studies showed a beneficial effect of mesenchymal stem cell administration in models of acute tubular injury and of endothelial progenitors in acute glomerular injury. Recent studies demonstrate the presence of resident stem cells within the adult kidney. These cells are capable, when injected in animals with acute tubular injury, to localize to renal compartments and contribute to regeneration. This review summarizes the current literature on the physiological role of endogenous stem cells in renal regeneration and on the therapeutic potential of exogenous stem cell administration. Moreover, critical points that still need clarification, such as the homing mechanisms of stem cells to injured tissue, the secreted factors underlying the paracrine/endocrine mechanisms and the long-term behaviour of in vivo administered stem cells, are discussed.