Ways and Means of Cellular Reconditioning for Kidney Regeneration

Ishiko S. · Goligorsky M.S.
American Journal of Nephrology, Vol. 53, No. 2-3, April 2022

Abstract

Background: Mitochondrial, lysosomal, and peroxisomal dysfunction; defective autophagy; mitophagy; and pexophagy, as well as the loss of glycocalyx integrity are known contributors to initiation and progression of diverse kidney diseases. Those cellular organelles are tightly interactive in health, and during development of a disease, damage in one may propagate to others. By extension, it follows that restoring an individual defect may culminate in a broader restorative spectrum and improvement of cell and organ functions.

Summary: A novel strategy of reconditioning cellular organellar dysfunction, which we define as refurbishment of pathogenically pivotal intra- or extracellular elements, damaged in the course of disease and impeding restoration, is briefly outlined in this overview. Individual therapeutic reconditioning approaches targeting selected organelles are cataloged. We anticipate that the proposed reconditioning strategy in the future may enrich the arsenal of regenerative medicine and nephrology.

Key Message: The arsenal of regenerative medicine and nephrology consisting of organ transplantation, use of stem cells, cell-free approaches, cell reprogramming strategies, and organ engineering has been enriched by the reconditioning strategy. The latter is based on the recognition of two facts that (a) impairment of diverse cellular organelles contributes to pathogenesis of kidney disease and (b) individual organelles are functionally interactively coupled, which explains the “domino effect” leading to their dysfunction. Reconditioning takes advantage of these facts and, while initially directed to restore the function of individual cellular organelles, culminates in the propagation of a therapeutic intervention to account for improved cell and organ function. Examples of such interventions are briefly summarized along the presentation of defective cellular organelles contributing to pathogenesis of kidney disease.

Excerpt from section Therapeutic Interventions to Preserve and Repair Glycocalyx

Another potentially promising therapeutic approach is represented by Endocalyx ProTM (Microvascular Health Solutions, Salt Lake City, [UT], USA), a combination of natural products each endowed with individual properties to accelerate restoration and prevent excessive degradation of glycocalyx. It contains brown seaweed extract called Laminaria japonica, rich in fucoidan sulfate – a hybrid of HS and CS. The fucoidan repairs the glycocalyx and prevents its breakdown by inhibiting heparanase activity. Another component is a high molecular weight hyaluronan. It is supplemented with glucosamine sulfate, providing the building blocks for glycocalyx synthesis. Further components include a proprietary blend of polyphenol and flavonoids with added superoxide dismutase and catalase (both from bitter melon concentrate).