Erratum to: J Nephrol DOI 10.1007/s40620-017-0384-z

Unfortunately, during the typesetting the word “MSC” has been removed in the original publication.


Page 3, under heading “Stem cell therapies” Para 2 should read as:


MSC migration in injured tissues is mediated by different mechanisms: CD44 binds hyaluronic acid thus recognizing any site of endothelial injury and basal membrane exposure [20]. Togel et al. demonstrated that VCAM-1 expression on activated endothelial cells is responsible for MSC localization in glomeruli and peritubular capillaries after renal ischemia [21]; the same authors investigated the chemokine axis CXCL12/CXCR4 as a possible trigger of MSC migration [21]. However, several authors questioned the relevance of MSC engrafting in injured organs and highlighted the release of endocrine/paracrine factors or transient membrane contact as mediators of MSC action [19]. Different studies support the endocrine theory: Bi et al. demonstrated that MSC conditioned medium is effective as stem cell infusion in IRI-AKI [22]; exploiting a similar model, it has been demonstrated that MSC release several vasculotrophic factors including vascular endothelial growth factor (VEGF)-alpha and hepatocyte growth factor (HGF) [23]. Other groups pointed out the relevance of contact-dependent conditioning of immune cells. These authors observed that MSC injected intravenously in healthy or organ-injured mice did not pass into the lung capillary system and disappeared after 24 h [24, 25]. Moreover, heat-inactivated MSC (i.e. unable to secrete paracrine factors) still modulated monocyte function and induced regulatory cytokine release similarly to normal MSC; nevertheless inactivated cells were not able to influence the B- and T-lymphocyte fate [25]. The role of monocytes/macrophages as mediators of MSC action has been further demonstrated by Geng et al. in a murine model of rhabdomyolysis: MSC were able to induce M2 regulatory macrophages and to preserve renal function. AKI was also prevented by injection of in vitro induced M2 cells but not in mice treated with MSC after macrophage depletion [26].


Page 7, under heading “Stem cell therapies” Para 3 should read as:


MSC have consistent regenerative and immune-modulatory proprieties and have been used as a therapeutic agent in several disease models including autoimmune disorders, tissue ischemia and degenerative diseases. Interestingly in onco-hematological patients who underwent HSC transplants, MSC from a third party donor were able to completely resolve drug resistant graft vs. host disease (GVHD). In vitro it has been observed that MSC inhibited patient lymphocyte proliferation by about 90% [46]. In KT, although strong preclinical data on MSC administration have been published [47], clinical evidence is still lacking. In a pilot study, Perico and colleagues infused autologous MSC as induction therapy at day 7 post-KT in 2 patients; unexpectedly, both patients developed a transient graft dysfunction associated with renal neutrophil infiltration and complement deposition as a consequence of a transitory intra-graft inflammatory state [48]. In a following study the same group assessed the safety of pre-transplant MSC infusion. Both protocols were associated with the long-term increase of circulating T regulatory cells and with the concomitant down-regulation of T memory and cytotoxic cells [48]. Several other studies on MSC infusion in KT patients are currently ongoing (see Tables 2, 3) and a few preliminary data are currently available. Reinders and coworkers used allogeneic MSC to treat patients with TCMR at early protocol biopsies (4 weeks and 6 months): 4/6 patients recovered without any functional or pathological impairment. However 3/6 patients experienced viral infections including 1 case of BK virus nephropathy [49].


Page 15, under heading “Conclusion” Para 3 should read as:


MSC are the most studied stem cell population in regenerative medicine and have been successfully applied to several preclinical AKI models; preliminary clinical data are encouraging but still inconclusive. Interestingly, some cell products such as growth factors and particularly extracellular vesicles are effective in vitro and in vivo and could represent a valuable alternative to cell infusion. In KT MSC are safe and effectively modulate the patient’s immune system; however, strong clinical outcomes are still far from being achieved. Some encouraging data about MSC come from other transplant models such as HCT. Additionally, HSC have been successfully used in KT to obtain immune chimerism and graft tolerance in small trials. Finally, immune regulatory cells are a further way to achieve immune tolerance in transplantation, and several protocols are available to induce ex vivo T-, B-, and M-reg cells; the clinical literature is growing in this field with encouraging data coming from different transplant models such as liver, kidney and hematopoietic cells. We can hypothesize that in the near future this fascinating “bench to bedside” journey of cell therapies may limit AKI mortality and promote KT tolerance leading to an improvement of graft survival.


The publisher would like to apologize for this error. The original article was corrected.