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Published on: September 11, 2020
Cell-Based Therapies in Acute Kidney Injury (AKI)
Daniel Patschan1, Ivo Buschmann2, Oliver Ritter2
1Innere Medizin I, Kardiologie, Angiologie, Nephrologie, Klinikum Brandenburg, Medizinische Hoch-schule Brandenburg, Brandenburg, Germany, d.patschan@gmail.com.
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.
Insights
Cell-based therapies show promise for acute kidney injury (AKI) by promoting kidney repair. While several stem cell types are effective experimentally, challenges remain for clinical application.
Area of Science:
- Nephrology
- Regenerative Medicine
- Cell Biology
Background:
- Acute kidney injury (AKI) is a common and serious condition in hospitalized patients with limited treatment options.
- Current therapies for AKI lack specific treatments to promote kidney regeneration or repair.
- Cell-based strategies have emerged as a promising experimental approach to improve AKI outcomes.
Purpose of the Study:
- To summarize the current understanding of four key cell populations investigated for AKI treatment: induced pluripotent stem cells (iPSCs), spermatogonial stem cells (SSCs), proangiogenic cells (PACs), and endothelial colony-forming cells (ECFCs).
- To discuss the mechanisms by which these cells exert protective effects in AKI, including direct cell incorporation and indirect mechanisms involving extracellular vesicles.
- To review the potential implications and challenges of translating these cell-based strategies into clinical practice for managing human AKI.
Main Methods:
- Review of experimental studies evaluating the efficacy of iPSCs, SSCs, PACs, ECFCs, and Mesenchymal Stem Cells (MSCs) in AKI models.
- Analysis of the documented effects of these cell types on kidney excretory and morphological parameters.
- Investigation of the underlying mechanisms of AKI protection, focusing on cell-mediated processes and extracellular vesicle cargo (e.g., micro-RNAs).
Main Results:
- Multiple stem cell types, including MSCs, have demonstrated the ability to stabilize kidney function and morphology in experimental AKI.
- Cell-derived extracellular vesicles play a crucial role in mediating indirect protective effects by delivering pro-regenerative molecules like micro-RNAs.
- These vesicles contribute to the stabilization of vascular and tubular functions within the damaged kidney.
Conclusions:
- Cell-based therapies, particularly those involving Mesenchymal Stem Cells (MSCs), are advancing towards clinical trials for AKI.
- Significant hurdles, including cell availability, immune tolerance, and functional competence, must be addressed for successful clinical implementation.
- Further research and development are essential to optimize cell-based strategies for the effective management of human AKI.
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