Cell-Based Therapies in Acute Kidney Injury (AKI)

Abstract

Acute kidney injury frequently occurs in hospitalized patients all over the world. The prognosis remains poor since specific therapies for promoting kidney regeneration/repair are still missing. In recent years cell-based strategies have improved AKI outcomes under experimental circumstances. Four groups of cells, each of them displaying certain biological and functional characteristics have been evaluated in AKI, induced Pluripotent Stem Cells (iPSCs), Spermatagonial Stem Cells (SSCs), Proangiogenic Cells (PACs) and Endothelial Colony Forming Cells (ECFCs), and Mesenchymal Stem Cells (MSCs). All of these have been documented to stabilize either parameters of kidney excretory dysfunction and/or certain morphological parameters. The mechanisms responsible for AKI protection include direct (cell incorporation) and indirect processes, the latter being mediated by humoral factors and particularly by the production of so-called extracellular vesicles. Cell-derived vesicular organelles have been shown to carry pro-regenerative micro-RNA molecules which stabilize the vascular and tubular function. The first trials in humans have been initiated, the majority of such trials employs MSCs. However, any transfer of cell-based strategies in the clinical practice is potentially associated with significant difficulties. These include cell availability, tolerance and competence. The article intends to summarize essential informations about all of the four populations mentioned above and to discuss implications for the management of human AKI.

A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury

“…6 Recently, studies on the treatment of AKI using MSCs have gained an increasing interest. [10][11][12][13] Treatment with MSCs has been reported to attenuate renal injury in a paracrine mode by secreting pro-mitotic, antiapoptotic, anti-inflammatory, and immunomodulatory factors. 14,15 As an example, an intravenous administration of IL-17A-pretreated MSCs in mice revealed a therapeutic effect in AKI 16 , demonstrating that immune modulation is one of the main mechanisms in MSCs treatment.…”

Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury

“…The two most important problems are related to the source of EPCs or other cell-types and the timing of cell administration. These aspects have recently been discussed [22].…”

“…Most studies have been performed in animals, however, particularly mesenchymal stem cells (MSCs) are currently being evaluated in human diseases including AKI [21,22]. In parallel, the mechanisms of therapeutic cell actions within the (post)ischemic or inflammatory microenvironment have gained the interest of researchers worldwide.…”

Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury

“…Cell-based therapies of ischemic and inflammatory diseases have increasingly been investigated in recent years. Most studies have been performed in animals, however, particularly mesenchymal stem cells (MSCs) are currently being evaluated in human diseases including AKI [ 21 , 22 ]. In parallel, the mechanisms of therapeutic cell actions within the (post)ischemic or inflammatory microenvironment have gained the interest of researchers worldwide.…”