Brief Report: Evaluating the Potential of Putative Pluripotent Cells Derived from Human Testis

Author:

Ko Kinarm123,Reinhardt Peter1,Tapia Natalia1,Schneider Rebekka K.4,Araúzo-Bravo Marcos J.1,Han Dong Wook15,Greber Boris1,Kim Julee1,Kliesch Sabine6,Zenke Martin78,Schöler Hans R.19

Affiliation:

1. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany

2. Center for Stem Cell Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Republic of Korea

3. Department of Neuroscience, School of Medicine, Konkuk University, Seoul, Republic of Korea

4. Institute of Pathology, University Hospital, RWTH Aachen University, Aachen, Germany

5. Department of Stem Cell Biology, SMART Institute of Advanced Biomedical Science, Konkuk University, Seoul, Republic of Korea

6. Department of Clinical Andrology, Centre for Reproductive Medicine and Andrology, University of Münster, Münster, Germany

7. Department of Cell Biology, Institute for Biomedical Engineering, Medical School, RWTH Aachen University, Aachen, Germany

8. Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany

9. Faculty of Medicine, University of Münster, Münster, Germany

Abstract

Abstract Human adult germline stem cells (haGSCs) were established from human testicular biopsies and were claimed to be pluripotent. Recently, the gene expression profile of haGSCs demonstrated that these cells presented with a fibroblast rather than a pluripotent identity. Nevertheless, haGSCs were reported to generate teratomas. In this report, we address this discrepancy. Instead of using haGSCs, which are no longer available for the stem cell community, we used a human testicular fibroblastic cell (hTFC) line that presents with a gene expression profile highly similar to that of haGSCs. Indeed, as shown by microarray analysis, the similarity between hTFCs and haGSCs is comparable to human embryonic stem cell (hESC) lines derived by different laboratories. We argue that the almost identical gene expression profile of hTFCs and haGSCs should result in a very similar if not identical differentiation potential. Strikingly, hTFCs were not able to generate teratomas after injection into nude mice. Instead, they formed a mesenchymal lesion that morphologically resembled the putative haGSC-derived teratomas reported previously. We conclude that haGSCs, which exhibit a profile similar to that of fibroblasts and could not generate teratomas, are not pluripotent. Future work will have to show if pluripotent cells can be derived from human testicular biopsies. Mouse work and certain testicular germ cell tumors indicate that this will be possible.

Funder

Max Planck Society

German Research Foundation

“Pluripotency and Cellular Reprogramming”

Federal Ministry of Education and Research

“Disease-specific iPS cells”

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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