KIDNEY TISSUE ENGINEERING
Author: Mridula Vats
The alternatives to replace kidney functions in humans include dialysis and allotransplantation. Transplantation of human kidneys is limited by the availability of donors. During the past few decades, many different approaches have been applied to tissue engineering the kidney. The goals include the recapitulation of renal filtration, resorptive and secretory functions, replacement of endocrine and metabolic activities. Patients with chronic kidney disease with deteriorated renal function are treated by dialysis or undergo surgical intervention for renal transplantation to reduce the risk of mortality. Dialysis is the major treatment modality for end-stage renal disease (ESRD), but it has some limitations in terms of morbidity, mortality, and cost.
Keywords: Human kidney, Cell-based strategies, Organ based strategies, Development of the bioartificial glomerulus.
The kidneys are solid organs critical to body homeostasis. They carry out excretory, regulatory, and endocrinologic functions. The excretory function is initiated by filtration of blood at the glomerulus, which is an enlargement of the proximal end of the tubule (PCT) incorporating a tuft of capillaries. The structure of the glomerulus is designed to remove toxic wastes from the plasma and retain important components. To replace the kidney's excretory function, an implantable kidney requires both a device to replace blood filtration performed by renal glomeruli and a device to replace the transport regulatory function of the renal tubule.
Accordingly, the kidney may be the first solid organ in which tissue engineering concepts can produce an implantable artificial device for in vivo replacement therapy, thereby replacing renal function in patients with ESRD to replace the need for long-term dialytic therapy. This technology can increase life expectancy, mobility and flexibility, increasing quality of life with less risk of infection, and reduced costs. This approach could be considered a cure rather than a treatment. With the advancement of the tissue engineering field, there is a need for the isolation and growth in vitro of specific cells from adult tissue. These cells possess stem cell-like characteristics with a high capacity for self-renewal and the ability to differentiate under specific conditions into specialized cells to develop correct structure and functional components of the organ. Stem cells have been widely studied in three adult mammalian tissues: the hematopoietic system, the epidermis, and the intestinal epithelium.
TISSUE ENGINEERING FORMULATION
To produce an implantable bioartificial kidney some important features of kidney tissue need to be appreciated. development of an artificial kidney using kidney cells and artificial membranes as the scaffold material should be considered a key step in kidney regeneration. The regulatory function of the kidney, especially concerning fluid and electrolyte homeostasis, is provided by the tubules hooked up to the glomerulus. The ultrafiltrate emanating from the glomerulus courses along the renal tubule, which reabsorbs fluid and solutes to finely minimize the excretion of various amounts of solutes and water in the final urine. The functional unit of the kidney is, therefore, composed of the filtering part, the glomerulus, and the regulatory part, the renal tubule. together they form a basic functioning unit of the kidney, called the nephron. To form a kidney a continuous hemofilter has been used as an alternative for glomerulus, and a tubular cell-attached hollow fibre module was used as the renal tubule. Cell-based strategies are based on the manipulation of one or several cell types, in various stages of development, to forming the essential components of the required tissue Organ-Based Strategies. Several laboratories are investigating embryonic organ-based approaches for kidney transplantation. As opposed to purely cell-based strategies, organ-based strategies take advantage of the fact that the multicellular embryonic metanephros has already started the coordinated process of differentiation and is programmed to develop into a fully functioning kidney. These approaches are modified concepts develop from cell-based kidney engineering strategies, and many of the extracellular matrix elements are similar.
Development of a bioartificial glomerulus
A bioartificial glomerulus, made up of a polymeric porous membrane and the endothelial cell layer should have some functional characteristics, including antithrombogenicity and increased permeability, for a long period.
There are several cell-based and organ-based approaches to kidney tissue engineering that take advantage of newly discovered developmental programs and experimental results. These approaches fundamentally begin with cells (either as individual cells or as structured within an organ) that are developed in a coordinated manner by growth factors within a biologically supportive matrix. Normal kidney development combines these various processes, and effective tissue engineering strategies will likely require similar integration.
Cieslinski, D. A., & Humes, H. D. (1994). Tissue engineering of a bioartificial kidney. Biotechnology and Bioengineering, 43 (7), 678–681. doi: 10.1002/bit.260430718 retrieved from onlinelibrary.wiley.com
Hammerman, M. R. (2003). Tissue engineering the kidney - The guest editor for this paper was Adrian Woolf, London, United Kingdom. Kidney International, 63 (4), 1195–1204. doi:10.1046/j.1523-1755.2003.00890.x retrieved from sciencedirect.com
Saito, A. (2014). Kidney tissue engineering. Tissue Engineering Using Ceramics and Polymers Buy Book
Steer, D. L., & Nigam, S. K. (2004). Developmental approaches to kidney tissue engineering. American Journal of Physiology-Renal Physiology, 286 (1). doi:10.1152/ajprenal.00167.2003 retrieved from journals.physiology.org
About the Author:
Mridula Vats, a graduate student of University School of Chemical Technology, GGSIP University, Delhi. She is pursuing her degree in biochemical engineering and is interested in biotechnology.