Some Induced Pluripotent Stem Cell Lines Cause Tumors When Transplanted into Mouse Cochleas


Japanese researchers have been carefully evaluating the safety of different stem cell lines to determine the tendency of these cells to form tumors when transplanted into mice. Such studies have made it abundantly clear that the tendency for cell lines to form tumors depends upon the cell line and where it is transplanted (see Blum & Benvenisty, The Tumorigenicity of Human Embryonic Stem Cells. Advances in Cancer Research, Volume 100, 2008, Pages 133–158). However, little is known about the cochlea and the tendency of stem cells to cause tumors when transplanted into the cochlea. Therefore, Takayuki Nakagawa of Kyoto University and his group examined the results of stem cell transplantation into mouse cochlea.

Nakagawa made it clear that his motivation for this work is to achieve successful stem cell transplantation into the cochlea to treat hearing loss. He said: “Hearing loss affect millions of people world-wide. Recent studies have indicated the potential of stem cell-based approaches for the regeneration of hair cells and associated auditory primary neurons. These structures are essential for hearing and defects result in profound hearing loss and deafness.”

In this study, Nakagawa’s group transplanted embryonic stem cells and three distinct clones of mouse induced pluripotent stem cells into the cochlea of adult mice. According to Nakagawa; “Our study examined using induced-pluripotent stem cells generated from the patient source to determine if they offer a promising alternative to ES (embryonic stem) cells. In addition, the potential for tumor risk from iPS cells needed clarification.”

Upon transplantation into the cochlea, each cell line showed a distinct ability to form neural structures and integrate into the adult cochlea four weeks after transplantation. Some cells showed poor survival in the cochlea and one induced pluripotent stem cell line formed tumors in the cochlea. “To our knowledge, this is the first documentation of teratoma formation in cochleae after cell transplantation,” said Nakagawa.

These data demonstrate the necessity of screen individual iPS cell lines before their use, since some lines have greater tumor-causing potential than others.  Furthermore, it essential for researchers to design and develop screens to eliminate tumorigenic iPS cell lines.

John Sladek from the University of Colorado School of Medicine said: “While this study do not look at the ability of the transplanted cells to repair hearing loss, it does provide insight into the survival and fate of transplanted cells.  It highlights the importance of factors such as knowing the original source of the cells and their degree of differentiation to enable the cells to be ranked in order of their likelihood of forming tumors.”