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Decellularized Kidney: A New Boost towards the Development of Bioartificial Transplantable Humanized Organ. Sandeep Kumar Vishwakarma 1 , Avinash Bardia 1 , P. Ganga Bhavani 1 , Nusrath Fathima 1 , Parveen N 1 , Mohd . Ishaq 1 , J . Venkateshwarulu 2 , Aleem Ahmed Khan 1
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Decellularized Kidney: A New Boost towards the Development of Bioartificial Transplantable Humanized Organ • Sandeep Kumar Vishwakarma1, AvinashBardia1, P. GangaBhavani1, Nusrath Fathima1, Parveen N1, Mohd. Ishaq1, J. Venkateshwarulu2, AleemAhmed Khan1 • 1Salar-E-MillatSultan Salahuddin Owaisi Centre for Cellular and Molecular Medicine, • 2 Department of Radiology, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500 058, Andhra Pradesh, INDIA. • aleem_a_khan@rediffmail.com • Introduction • Transplantation remains the only available curative treatment for patients with end stage renal diseases however, hemodialysis has increased the survival rate little longer. • Stagnant donor organ (Kidney) numbers have increased waiting times to over 3 years and waitlist mortality to 5–10%. • Despite advances in renal transplant immunology, 20% of recipients experience an episode of acute rejection within 5 years of transplantation, and approximately 40% of recipients die or lose graft function within 10 years after transplantation. • Creation of a bioengineered kidney could theoretically bypass these problems by providing an autologous graft on demand. • Technology of removing cells and its components from the organ followed by repopulation of cells within the organ scaffold is termed as Decellularization and Recellularization. • This technology produces 3-D architecture and vascular tree which provides inducing factors for the engraftment, proliferation and survival of the cells. • Advantages of decellularized organs • Solves the problem for life long use of immunosuppressant after organ transplant. • Reduces the risk of rejection. • Provides important signal for the engraftment, survival and function of transplanted cells in new borne organ. • Allows rapid delivery of oxygen and nutrients after recellularization and reconnection to the circulation. • Materials and methods • Perfusion decellularization of rat kidneys were performed in accordance with Animal Welfare Act and approved by institutional ethics committee. • Kidney was retrieved from rat abdomen after systemic heparinization and transection of renal artery, vein and ureter. • Kidney decellularization was performed through renal artery using a combination of SDS and Triton-X-100 at 30mm Hg pressure. • Vascular integrity of whole decellularized kidney was checked by contrast imaging (angiogram). • Further the decellularized Kidney bioscaffold was characterized to ensure complete removal of cells retaining the complete vascular architecture and connective tissues as scaffold. • Results • The decellularized Kidney vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. • Kidney capsule was found to be intact after decellularization . • Extracellular matrix and vascular network within the decellularized kidney was retained intact without damage. Major challenges • Refinement of treatments to preserve the ECM • Appropriate 3-D spatial organization of cells • Innervations • Generation of Lymphatic system • Maintenance of vascular network • Product standards that assess all scaffold criteria • Optimization of experiments for system of interest • Standardized lab animal testing and quality standard • Differences in specimens, agents and protocols • Post-transplantation analysis Equipment set-up for perfusion decellularization of whole kidney • Conclusion • The study has demonstrated a potential approach for the development of natural whole Kidney scaffold in the fabrication of kidney tissues and whole organ support to provide a resource for the treatment of end stage renal diseases.