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Hematology Reports
Volume 5
Issue 2
10.4081/hr.2013.e9
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Hematology Reports is published by MDPI from Volume 14 Issue 1 (2022). Previous articles were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence, and they are hosted by MDPI on mdpi.com as a courtesy and upon agreement with PAGEPress.
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Article

Repression of Factor VIII Inhibitor Development with Apoptotic Factor VIII-Expressing Embryonic Stem Cells

by
Yoshihiko Sakurai
1,2,*,
Shogo Kasuda
3,
Kohei Tatsumi
1,
Tomohiro Takeda
1,
Junko Kato
1,
Atsushi Kubo
4 and
Midori Shima
1
1
Departments of Pediatrics, Nara Medical University School of Medicine, Kashihara 634-8521, Japan
2
Department of Pediatrics, Nara Prefectural Mimuro Hospital, 1-14-16 Mimuro, Sango, Ikoma-gun, Nara 636-0802, Japan
3
Legal Medicine, Nara Medical University School of Medicine, Kashihara 634-8521, Japan
4
First Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8521, Japan
*
Author to whom correspondence should be addressed.
Hematol. Rep. 2013, 5(2), 30-33; https://doi.org/10.4081/hr.2013.e9
Submission received: 7 December 2012 / Revised: 10 April 2013 / Accepted: 29 April 2012 / Published: 1 July 2013

Abstract

Development of factor VIII (fVIII)-neutralizing antibodies, called inhibitors, is a challenging problem in the management of hemophilia A patients. We explored the possibility of pretreatment with apoptotic fVIII-expressing embryonic stem (ES) cells to prevent the development of fVIII inhibitors. Murine ES cells integrated with the human F8 gene were differentiated into embryoid bodies, dissociated to a single cell suspension, subjected to hypo-osmotic shock to induce apoptosis, and intraperitoneally injected into hemophilia A mice. Inhibitors were induced by periodic intraperitoneal injections of recombinant human fVIII (rhfVIII). In the groups in which intraperitoneal injections of rhfVIII began at 1–3 weeks after pretreatment, the titers of inhibitors were significantly lower after the third administration of rhfVIII compared with that in the control group in which apoptotic Ainv18 ES cells (without the human F8 gene) were used for pretreatment, and continued to show lower levels until the sixth administration of rhfVIII. These results suggest that pretreatment with apoptotic hfVIII-expressing ES cells might be promising for the prevention of fVIII inhibitor development in hemophilia A patients.
Keywords: hemophilia; fVIII inhibitors; prevention; embryonic stem cells; apoptosis hemophilia; fVIII inhibitors; prevention; embryonic stem cells; apoptosis

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MDPI and ACS Style

Sakurai, Y.; Kasuda, S.; Tatsumi, K.; Takeda, T.; Kato, J.; Kubo, A.; Shima, M. Repression of Factor VIII Inhibitor Development with Apoptotic Factor VIII-Expressing Embryonic Stem Cells. Hematol. Rep. 2013, 5, 30-33. https://doi.org/10.4081/hr.2013.e9

AMA Style

Sakurai Y, Kasuda S, Tatsumi K, Takeda T, Kato J, Kubo A, Shima M. Repression of Factor VIII Inhibitor Development with Apoptotic Factor VIII-Expressing Embryonic Stem Cells. Hematology Reports. 2013; 5(2):30-33. https://doi.org/10.4081/hr.2013.e9

Chicago/Turabian Style

Sakurai, Yoshihiko, Shogo Kasuda, Kohei Tatsumi, Tomohiro Takeda, Junko Kato, Atsushi Kubo, and Midori Shima. 2013. "Repression of Factor VIII Inhibitor Development with Apoptotic Factor VIII-Expressing Embryonic Stem Cells" Hematology Reports 5, no. 2: 30-33. https://doi.org/10.4081/hr.2013.e9

APA Style

Sakurai, Y., Kasuda, S., Tatsumi, K., Takeda, T., Kato, J., Kubo, A., & Shima, M. (2013). Repression of Factor VIII Inhibitor Development with Apoptotic Factor VIII-Expressing Embryonic Stem Cells. Hematology Reports, 5(2), 30-33. https://doi.org/10.4081/hr.2013.e9

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