What is it about?
Our study describes, for the first time, a new regenerative mechanism, driven by the toll-like receptor 2 (TLR2), by which tubular ARPCs induce regeneration of renal proximal tubular epithelial cells (RPTECs). We studied the influence of ARPCs on the regenerative process of cisplatin-injured RPTECs and we found several conceptual advance and mechanistic insights: - tubular ARPCs (tARPCs), but not glomerular ARPCs, protected RPTECs by preventing cisplatin-induced apoptosis and enhancing proliferation of survived cells - tARPCs, but not glomerular ARPCs were resistant to cisplatin apoptotic effect - it is necessary that the damage is detected through the TLR2 to have the regenerative effect by tARPCs. We found that tARPCs operated through the secretion of both inhibin-A chemokines and microvesicle-vehicled decorin, inhibin-A and decorin mRNA, all dependent on the activation of TLR2 expressed by renal progenitors.
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Why is it important?
Our results, identifying a precise tARPC paracrine reparative mechanism, help to conciliate discrepancies, recently emerged in the scientific literature, between the regenerative role of stem/progenitor cells and the latest findings, showing that the regeneration by surviving tubular epithelial cells is the predominant mechanism of repair but not involving renal progenitors dividing in response to injury. Moreover, we assembled a biocompatible polysaccharide core-shell system able to include regenerative molecules, as Inhb-A and decorin, in its alginate hydrogel core. Unexpectedly, in vitro administration of SVs carrying Inhb-A and decorin gave the same functional effect of the two proteins free in the medium. Instead, SVs could be very useful in vivo since they can be decorated with proteins recognized by specific cells (i.e. RPTECs) and can ensure the specificity of the delivery of regenerative molecules
Perspectives
Results of our work support the idea of therapeutic strategies to improve the renal repair ability exploiting the resident renal progenitors, for example acting on the TLR2 signaling or directly shuttling reparative molecules using SVs capable to target specific renal compartments. This concept is alternative to the idea to inject exogenous stem cells and can overcome problems related to the uncontrolled or misdirect growth of stem cells.
Fabio Sallustio
Universita degli Studi di Bari Aldo Moro
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This page is a summary of: Inhibin-A and Decorin Secreted by Human Adult Renal Stem/Progenitor Cells Through the TLR2 Engagement Induce Renal Tubular Cell Regeneration, Scientific Reports, August 2017, Springer Science + Business Media,
DOI: 10.1038/s41598-017-08474-0.
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