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Risk of Teratoma Formation After Transplantation of Induced Pluripotent Stem CellsTeratoma From Induced Pluripotent Stem Cells FREE TO VIEW

Shigeo Masuda, MD, PhD
Author and Funding Information

From the Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology; the Foundation for Biomedical Research and Innovation; and the Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.

Correspondence to: Shigeo Masuda, MD, PhD, Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; e-mail: smasuda-tky@umin.ac.jp


Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(4):1120-1121. doi:10.1378/chest.11-2790
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To the Editor:

I read with great interest the article by Yang et al1 in a recent issue of CHEST (November 2011), which clearly demonstrates that IV administration of induced pluripotent stem (iPS) cells reduces endotoxin-induced acute lung injury in mice. Regarding the possibility of teratoma formation2 after transplantation of iPS cells, I have several concerns from the viewpoint of human clinical application in the future.

First, it would be interesting to know the reason why there would be no teratoma formation in the present study. Recently, it has been revealed that mouse iPS cell-derived cells have immunogenicity and can be rejected immunologically, even when transplanted into syngenic mice,3 because several genes are found to be overexpressed in teratomas, which will induce immune responses. On the other hand, it has been shown that embryonic stem (ES) cell-derived cells have no immunogenicity and can be engrafted as teratomas. In the present study, it is not clear whether the lack of teratoma formation is attributable to the types of cells the authors used or the method they used to inject cells. Control experiments, either by using ES cells or by direct intratracheal injection, would clarify this point.

Second, it would be safer to inject differentiated cells rather than undifferentiated iPS cells in order to avoid potential teratoma formation. Recently, there has been a commentary by Okita et al4 against the article describing immunogenicity of iPS cells.3 The commentary4 mentioned that, for human medical applications, iPS-derived cells (ie, differentiated cells), but not iPS cells themselves (ie, undifferentiated cells), would be injected into patients. Based on this philosophy, is there the same efficacy, even when differentiated cells from iPS cells would be administered into mice with endotoxin-induced acute lung injury?

Finally, as mentioned by the authors, because autologous iPS cells would be hardly available for patients with acute lung injury, allogeneic iPS or ES cells should be applied. How about allogeneic transplantation in mice? The use of immunosuppressants for allotransplantation would be prohibited because of the risk of endotoxin-induced acute lung injury. If acute rejection within 24 or 48 h is not found to be a serious problem for efficacy, allotransplantation without immunosuppressants would be suitable for endotoxin-induced acute lung injury.

Yang K-Y, Shih H-C, How C-K, et al. IV delivery of induced pluripotent stem cells attenuates endotoxin-induced acute lung injury in mice. Chest. 2011;1405:1243-1253 [CrossRef] [PubMed]
 
Masuda S, Hanazono Y. Induced pluripotent stem cells in long-QT syndrome. N Engl J Med. 2011;3642:181-182 [CrossRef] [PubMed]
 
Zhao T, Zhang ZN, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature. 2011;4747350:212-215 [CrossRef] [PubMed]
 
Okita K, Nagata N, Yamanaka S. Immunogenicity of induced pluripotent stem cells. Circ Res. 2011;1097:720-721 [CrossRef] [PubMed]
 

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References

Yang K-Y, Shih H-C, How C-K, et al. IV delivery of induced pluripotent stem cells attenuates endotoxin-induced acute lung injury in mice. Chest. 2011;1405:1243-1253 [CrossRef] [PubMed]
 
Masuda S, Hanazono Y. Induced pluripotent stem cells in long-QT syndrome. N Engl J Med. 2011;3642:181-182 [CrossRef] [PubMed]
 
Zhao T, Zhang ZN, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature. 2011;4747350:212-215 [CrossRef] [PubMed]
 
Okita K, Nagata N, Yamanaka S. Immunogenicity of induced pluripotent stem cells. Circ Res. 2011;1097:720-721 [CrossRef] [PubMed]
 
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