Cell therapy: leveraging nature's therapeutic potential.

Abstract

Cell therapy is one of the most exciting fields in translational medicine. It stands at the intersection of a variety of rapidly developing scientific disciplines: stem cell biology, immunology, tissue engineering, molecular biology, biomaterials, transplantation biology, regenerative medicine, and clinical research. Cell-based therapy may develop into a new therapeutic platform to treat a vast array of clinical disorders. Blood transfusions and bone marrow transplantation are prime examples of the successful application of cell-based therapeutics, but recent advances in cellular and molecular biology have expanded the potential applications of this approach. The excitement surrounding this area arises from the successful application of recombinant genetic engineering to produce a variety of therapeutics, such as human erythropoietin and insulin. Although this molecular technology has proven successful, the opportunities to use it have been limited, because most common disease processes are not due to the deficiency of a single protein but develop due to alterations in the complex interactions of a variety of cell components. In these complex situations, cell-based therapy may prove to be a more successful strategy by providing a dynamic, interactive, and individualized therapeutic approach that responds to the pathophysiological condition of the patient. In this regard, cells may provide innovative methods for drug delivery of biologics, immunotherapy, and tissue regenerative or replacement engineering (1,2). The translation of this discipline has tremendous potential, but technological issues need to be overcome in many applications. Many cell-based indications are already being evaluated in the clinic; therefore, the field appears to be on the threshold of a number of successes. In this issue of JASN, Saito et al. (3) present another potential application of cells to degrade an endogenously produced uremic toxin. Beta2-microglobulin (2-m) accumulates in patients with end-stage renal disease (ESRD) because its degradative pathway of glomerular filtration and proximal tubule cell metabolism is severely diminished. The buildup of 2-m as amyloid deposits in the joints of ESRD patients often results in a debilitating arthritis (4). The authors of this article demonstrate that an epithelially derived tumor cell line called L2 cells that was implanted and expanded into tumor nodules in nude mice was able to take up and degrade circulating 2-m in acutely nephrectomized animals. L2 cells possess megalin, a cell surface ligand that binds a large number of low–molecular weight proteins (LMWP), including 2-m, resulting in catabolism of this uremic toxin. The translation of this cell-based approach to the clinic, however, requires solving a number of technological hurdles common to other cell therapeutic approaches. The first broad-based application of cell therapy may be the delivery of biologic compounds as drugs. Current biologic therapy requires multiple steps: production of the protein in cultured cells, purification of the compound, and then administration to a patient. Cell therapy is a more direct approach to biologic treatment and may also be advantageous in delivering higher concentrations with site specificity and improved patient compliance. The biologic may be delivered continuously,