Contaminated cells force retraction of Blood paper
The article, “Oxygen-regulated expression of the erythropoietin gene in the human renal cell line REPC,” came from a team at Universität Duisburg-Essen, in Germany, and has been cited 21 times, according to Thomson Scientific’s Web of Knowledge. Here’s the abstract:
Erythropoietin (EPO), the key hormone in red blood cell renewal, is mainly produced in the adult kidney. Anemia and hypoxia substantially enhance EPO expression to increase erythropoiesis. Investigations of the cellular physiology of renal EPO production have been hampered by the lack of an adequate human cell line. In the present study, we present the human kidney cell line REPC (for renal Epo-producing cells), established from an explanted human kidney exhibiting EPO gene expression and release of the EPO protein in an oxygen-dependent manner. Hypoxic induction of EPO mRNA showed the typical transient increase and peak in expression after 36 hours under continuous conditions of hypoxia. Bioactive EPO protein accumulated in the culture supernatant. The induction of EPO gene expression in REPCs critically depended on the activation of hypoxia-inducible transcription factors (HIFs). SiRNA treatment revealed that the expression of EPO was largely dependent on the activation of the transcription factor complex HIF-2. In addition, hepatic nuclear factor 4α was shown to be critically involved in hypoxia-induced renal EPO expression. Using the human kidney cell line REPC, we provide for the first time a powerful tool with which to study the cellular and molecular regulation of renal EPO production.
Turns out those cells weren’t what the researchers thought they were. Per the retraction notice:
The Editors of Blood wish to retract the above-mentioned publication. The paper reported on a permanent human renal cell line, which was established from the tumor-free renal tissue of an anonymized male patient suffering from a kidney tumor. The cells were capable of hypoxia-inducible erythropoietin production – therefore termed Renal Erythropoietin Producing Cells (REPC) – showed features of neuronal cells, and were negative hepatitis virus B.
After publication the authors have freely provided the cells to a number of researchers who requested them. One of the collaborators has brought to the authors’ attention that REPC were contaminated with human Hep3B cells. Upon this, the authors have externally tested the cells including frozen aliquots of the youngest passage that was left after treating all REPC for mycoplasma infection. DNA profiling using 8 different and highly polymorphic short tandem repeat (STR) loci revealed that the REPC were cross-contaminated with Hep3B. STR profiles of the used cells were matching the STR reference profile of the cell line Hep3B as indicated by a search of the STR database from cell banks ATCC (USA), HPACC (UK), JCRB (Japan), RIKEN (Japan), KCLB (Korea) and DSMZ (Germany). Upon this, all groups who received cells were immediately informed about the contamination and have been asked to send back aliquots of the cells. These were again externally tested, but the contamination was confirmed. One collaborating group had identified different cell phenotypes in the REPC cultures by immunohistochemistry and tried to isolate single clones from the phenotypically different appearing cells. The latest STR profiling of the two clones, however, also revealed persisting cross-contamination with Hep3B.
Thus, the authors notified Blood that they can currently neither provide cells that were described in the original publication nor reproduce the original results due to the lack of the cells. Because the cells should have served as an important new in vitro model or renal cells to study erythropoietin production, the authors and the Journal feel obliged to retract the above publication to avoid any further confusion about the existence of a permanent human renal erythropoietin-producing cell line. The authors apologize for any inconvenience that the research community may have faced with REPC obtained directly from them or from other sources.
All authors agree to the retraction.