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Kuang-Yao Yang, MD, PhD; Shih-Hwa Chiou, MD, PhD
Author and Funding Information

Department of Chest Medicine (Dr Yang) and Department of Medical Research and Education (Dr Chiou), Taipei Veterans General Hospital; and Institute of Clinical Medicine (Drs Yang and Chiou) and Institute of Pharmacology (Dr Chiou), School of Medicine, National Yang-Ming University.

Correspondence to: Kuang-Yao Yang, MD, PhD, Department of Chest Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd, Taipei 11217, Taiwan; e-mail: kyyang@vghtpe.gov.tw


Financial/nonfinancial disclosures:The authors have 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):1121. doi:10.1378/chest.11-3093
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To the Editor:

We thank Dr Masuda for his interest in our recent article in CHEST.1 Dr Masuda expressed relevant opinions on the potential mechanism of teratoma formation after transplantation of induced pluripotent stem (iPS) cells.

In a recent study, Zhao et al2 examined the immunogenicity of iPS cells between embryonic stem (ES) cells isolated from inbred C57BL/6 (B6) mice and allogeneic ES cells from 129/SvJ mice. Whereas injection of ES cells from B6 mice induced teratoma formation, allogeneic ES cells derived from 129 SvJ were unable to form teratomas due to immune rejection by the recipients. A subsequent experiment was performed to evaluate teratoma formation in reprogrammed iPS cells from B6 mice by either the retroviral approach (ViPS cells) or a novel episomal approach (EiPS cells). In contrast to teratoma formation in ES cells from B6 mice, teratomas were immune rejected in reprogrammed iPS cells by B6 recipients in both the ViPS cell and EiPS cell methods. A T-cell-dependent immune response was shown in the teratomas that resulted in tissue damage and teratoma regression.2 Although teratoma formation was demonstrated by both methods, the ViPS cells method appeared to be superior at eliciting a greater immune response than the EiPS cells method. In addition, the inflammatory microenvironment and circulatory immune system may facilitate the engraftment of transplanted iPS cells but prevent teratoma formation.

Moreover, to decrease the potential of teratoma formation in iPS cell-based therapy, a recent commentary by Okita et al3 examined the use of iPS cell-derived differentiated cells instead of undifferentiated iPS cells for transplantation in medical applications. Differentiated cells, such as ES cell-derived alveolar epithelial type 2 cells,4 have shown a therapeutic effect in mice with acute lung injury (ALI). However, the immunogenicity of iPS cell-derived differentiated cells in autogenic or allogenic transplantation is still unclear. Therefore, further studies are warranted to explore the immune response among transplanted iPS cell-differentiated cells, inflammatory cells, and host cells in ALI.

Dr Masuda mentioned the therapeutic potential of allotransplantation with or without immunosuppressants for endotoxin-induced ALI. Interestingly, immunosuppressants may enhance the differentiation of iPS cells. Fujiwara et al5 have reported that cyclosporine drastically increases cardiomyocyte induction from human iPS cells, and these cells showed various cardiac marker expressions and ultrastructural features of cardiomyocytes.5

In conclusion, we agree that autologous iPS cell therapy currently offers many technical challenges for the treatment of patients with ALI. However, a better understanding of the reprogramming of iPS cells, graft rejection, and teratoma formation may improve the potential of this technology for the treatment of patients with ALI.

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]
 
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]
 
Wang D, Morales JE, Calame DG, Alcorn JL, Wetsel RA. Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice. Mol Ther. 2010;183:625-634 [CrossRef] [PubMed]
 
Fujiwara M, Yan P, Otsuji TG, et al. Induction and enhancement of cardiac cell differentiation from mouse and human induced pluripotent stem cells with cyclosporin-A. PLoS ONE. 2011;62:e16734 [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]
 
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]
 
Wang D, Morales JE, Calame DG, Alcorn JL, Wetsel RA. Transplantation of human embryonic stem cell-derived alveolar epithelial type II cells abrogates acute lung injury in mice. Mol Ther. 2010;183:625-634 [CrossRef] [PubMed]
 
Fujiwara M, Yan P, Otsuji TG, et al. Induction and enhancement of cardiac cell differentiation from mouse and human induced pluripotent stem cells with cyclosporin-A. PLoS ONE. 2011;62:e16734 [CrossRef] [PubMed]
 
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