BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned in view of their relatively low frequency. Here, we hypothesize that the severity of renal damage and the postischemic recovery time are determinants of tubular bone marrow-derived cell (BMDC) engraftment. METHODS: We used a model of unilateral renal I/R in F344 rats reconstituted with R26-human placental alkaline phosphatase (hPAP) transgenic bone marrow, in which we quantified and characterized tubular BMDC engraftment with increasing severity of damage and in time. RESULTS: After I/R injury, BMDC engrafted the tubular epithelium and acquired an epithelial phenotype. Tubular epithelial BMDC engraftment increased with longer ischemic time, indicating that tubular epithelial BMDC engraftment increases with the severity of damage. The number of circulating progenitor cells doubled early after I/R injury and was followed by a transient increase in tubular epithelial BMDC engraftment. The latter positively correlated with morphological recovery of the kidney over time. CONCLUSION. The extent of tubular BMDC engraftment depends on the severity of renal damage and follows a distinct time course after I/R injury. Therefore, the severity of damage and time course need to be taken into account when interpreting data on the role of tubular BMDC engraftment in renal repair after I/R injury.
BACKGROUND:Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned in view of their relatively low frequency. Here, we hypothesize that the severity of renal damage and the postischemic recovery time are determinants of tubular bone marrow-derived cell (BMDC) engraftment. METHODS: We used a model of unilateral renal I/R in F344 rats reconstituted with R26-human placental alkaline phosphatase (hPAP) transgenic bone marrow, in which we quantified and characterized tubular BMDC engraftment with increasing severity of damage and in time. RESULTS: After I/R injury, BMDC engrafted the tubular epithelium and acquired an epithelial phenotype. Tubular epithelial BMDC engraftment increased with longer ischemic time, indicating that tubular epithelial BMDC engraftment increases with the severity of damage. The number of circulating progenitor cells doubled early after I/R injury and was followed by a transient increase in tubular epithelial BMDC engraftment. The latter positively correlated with morphological recovery of the kidney over time. CONCLUSION. The extent of tubular BMDC engraftment depends on the severity of renal damage and follows a distinct time course after I/R injury. Therefore, the severity of damage and time course need to be taken into account when interpreting data on the role of tubular BMDC engraftment in renal repair after I/R injury.
Authors: Arpita Baisantry; Sagar Bhayana; Song Rong; Esther Ermeling; Christoph Wrede; Jan Hegermann; Petra Pennekamp; Inga Sörensen-Zender; Hermann Haller; Anette Melk; Roland Schmitt Journal: J Am Soc Nephrol Date: 2015-10-20 Impact factor: 10.121
Authors: Daniela Zwolanek; María Satué; Verena Proell; José R Godoy; Kathrin I Odörfer; Magdalena Flicker; Sigrid C Hoffmann; Thomas Rülicke; Reinhold G Erben Journal: JCI Insight Date: 2017-10-19
Authors: Eman Mostafa Sadek; Noha Mohamed Afifi; Lamiaa Ibrahim Abd Elfattah; Manal Ali Abd-El Mohsen Journal: Int J Stem Cells Date: 2013-05 Impact factor: 2.500
Authors: George Haddad; Malte Kölling; Urs A Wegmann; Angela Dettling; Harald Seeger; Roland Schmitt; Inga Soerensen-Zender; Hermann Haller; Andreas D Kistler; Anne Dueck; Stefan Engelhardt; Thomas Thum; Thomas F Mueller; Rudolf P Wüthrich; Johan M Lorenzen Journal: J Am Soc Nephrol Date: 2021-01-21 Impact factor: 10.121