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Dive into the research topics where Kyoko Sasaki is active.

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Featured researches published by Kyoko Sasaki.


Stem Cells | 2006

Improved safety of hematopoietic transplantation with monkey embryonic stem cells in the allogeneic setting

Hiroaki Shibata; Naohide Ageyama; Yujiro Tanaka; Yukiko Kishi; Kyoko Sasaki; Shinichiro Nakamura; Shin-ichi Muramatsu; Satoshi Hayashi; Yoshihiro Kitano; Keiji Terao; Yutaka Hanazono

Cynomolgus monkey embryonic stem cell (cyESC)‐derived in vivo hematopoiesis was examined in an allogeneic transplantation model. cyESCs were induced to differentiate into the putative hematopoietic precursors in vitro, and the cells were transplanted into the fetal cynomolgus liver at approximately the end of the first trimester (n = 3). Although cyESC‐derived hematopoietic colony‐forming cells were detected in the newborns (4.1%–4.7%), a teratoma developed in all newborns. The risk of tumor formation was high in this allogeneic transplantation model, given that tumors were hardly observed in immunodeficient mice or fetal sheep that had been xeno‐transplanted with the same cyESC derivatives. It turned out that the cyESC‐derived donor cells included a residual undifferentiated fraction positive for stage‐specific embryonic antigen (SSEA)‐4 (38.2% ± 10.3%) despite the rigorous differentiation culture. When an SSEA‐4‐negative fraction was transplanted (n = 6), the teratoma was no longer observed, whereas the cyESC‐derived hematopoietic engraftment was unperturbed (2.3%–5.0%). SSEA‐4 is therefore a clinically relevant pluripotency marker of primate embryonic stem cells (ESCs). Purging pluripotent cells with this surface marker would be a promising method of producing clinical progenitor cell preparations using human ESCs.


Transplantation | 2003

Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells

Takayuki Asano; Naohide Ageyama; Koichi Takeuchi; Mikio Momoeda; Yoshihiro Kitano; Kyoko Sasaki; Yasuji Ueda; Yutaka Suzuki; Yasushi Kondo; Ryuzo Torii; Mamoru Hasegawa; Shigeo Ookawara; Kiyonori Harii; Keiji Terao; Keiya Ozawa; Yutaka Hanazono

Background. To achieve human embryonic stem (ES) cell-based transplantation therapies, allogeneic transplantation models of nonhuman primates would be useful. We have prepared cynomolgus ES cells genetically marked with the green fluorescent protein (GFP). The cells were transplanted into the allogeneic fetus, taking advantage of the fact that the fetus is so immunologically immature as not to induce immune responses to transplanted cells and that fetal tissue compartments are rapidly expanding and thus providing space for the engraftment. Methods. Cynomolgus ES cells were genetically modified to express the GFP gene using a simian immunodeficiency viral vector or electroporation. These cells were transplanted in utero with ultrasound guidance into the cynomolgus fetus in the abdominal cavity (n=2) or liver (n=2) at the end of the first trimester. Three fetuses were delivered 1 month after transplantation, and the other, 3 months after transplantation. Fetal tissues were examined for transplanted cell progeny by quantitative polymerase chain reaction and in situ polymerase chain reaction of the GFP sequence. Results. A fluorescent tumor, obviously derived from transplanted ES cells, was found in the thoracic cavity at 3 months after transplantation in one fetus. However, transplanted cell progeny were also detected (∼1%) without teratomas in multiple fetal tissues. The cells were solitary and indistinguishable from surrounding host cells. Conclusions. Transplanted cynomolgus ES cells can be engrafted in allogeneic fetuses. The cells will, however, form a tumor if they “leak” into an improper space such as the thoracic cavity.


Gene Therapy | 2005

Efficient and stable Sendai virus-mediated gene transfer into primate embryonic stem cells with pluripotency preserved.

Kyoko Sasaki; Makoto Inoue; Hiroaki Shibata; Yasuji Ueda; Shin-ichi Muramatsu; Takashi Okada; Mamoru Hasegawa; Keiya Ozawa; Yutaka Hanazono

Efficient gene transfer and regulated transgene expression in primate embryonic stem (ES) cells are highly desirable for future applications of the cells. In the present study, we have examined using the nonintegrating Sendai virus (SeV) vector to introduce the green fluorescent protein (GFP) gene into non-human primate cynomolgus ES cells. The GFP gene was vigorously and stably expressed in the cynomolgus ES cells for a year. The cells were able to form fluorescent teratomas when transplanted into immunodeficient mice. They were also able to differentiate into fluorescent embryoid bodies, neurons, and mature blood cells. In addition, the GFP expression levels were reduced dose-dependently by the addition of an anti-RNA virus drug, ribavirin, to the culture. Thus, SeV vector will be a useful tool for efficient gene transfer into primate ES cells and the method of using antiviral drugs should allow further investigation for regulated SeV-mediated gene expression.


Cloning and Stem Cells | 2009

Improved efficacy and safety of in utero cell transplantation in sheep using an ultrasound-guided method.

Yoshikazu Nagao; Tomoyuki Abe; Hideaki Hasegawa; Yujiro Tanaka; Kyoko Sasaki; Yoshihiro Kitano; Satoshi Hayashi; Yutaka Hanazono

In the present study, we investigated the suitability of two methods for the transplantation of cells into ovine fetuses. The first method was an ultrasound-guided cell injection via the uterine wall. The second involved hysterotomic cell injection with an incision in the uterine wall exposing the amnion. Monkey embryonic stem (ES) cell-derived hematopoietic cells were used as donor cells. After transplantation, the abortion rate associated with the hysterotomic injection method was significantly higher than that of the ultrasound-guided injection method (8/13 versus 4/24; P < 0.01). The fetuses were delivered to examine the engraftment of transplanted monkey hematopoietic cells. Monkey cells were detected in one of the five animals (20%) in the hysterotomic injection group, and 14 of 20 animals (70%, P < 0.05) in the ultrasound-guided injection group. Therefore, the ultrasound-guided method was effectively shown to be minimally invasive for in utero transplantation and can produce a higher rate of engraftment for transplanted cells.


Annals of Plastic Surgery | 2009

Expanded narrow subcutaneous-pedicled island forehead flap for reconstruction of the forehead.

Mutsumi Okazaki; Kazuki Ueda; Kyoko Sasaki; Tomohiro Shiraishi; Masakazu Kurita; Kiyonori Harii

To reconstruct the subsequent defects after resection of a unilateral large forehead lesion, we devised a revised method, “expanded narrow subcutaneous-pedicled island forehead flap.” After unilateral forehead skin was expanded by a tissue expander, the flap was designed on the upper half of the expanded forehead skin nourished by the subcutaneous adipomuscular pedicle, including the supratrochlear or supraorbital artery. The elevated flap was then transposed or rotated 180 degrees toward the defect. The donor site was closed with upward advancement of the lower half of the expanded skin. Four patients were treated with this method. The flaps survived completely without serious complications, and acceptable results were obtained in all patients. This method has the advantage of increased freedom of flap design and transfer, providing an effective use of unaffected skin, less scars left on the forehead, and less formation of the dog-ear compared with the conventional procedure.


Stem Cells and Development | 2008

Sustained Macroscopic Engraftment of Cynomolgus Embryonic Stem Cells In Xenogeneic Large Animals After In Utero Transplantation

Yujiro Tanaka; Shinichiro Nakamura; Hiroaki Shibata; Yukiko Kishi; Tamako Ikeda; Shigeo Masuda; Kyoko Sasaki; Tomoyuki Abe; Satoshi Hayashi; Yoshihiro Kitano; Yoshikazu Nagao; Yutaka Hanazono

Because embryonic stem (ES) cells are able to proliferate indefinitely and differentiate into any type of cell, they have the potential for providing an inexhaustible supply of transplantable cells or tissues. However, methods for the in vitro differentiation of human ES cells are still quite limited. One possible strategy would be to generate differentiated cells in vivo. In view of future clinical application, we investigated the possibility of using xenogeneic large animals for this purpose. We transplanted nonhuman primate cynomolgus ES cells into fetal sheep at 43-67 gestational days (full term 147 days, n=15). After birth, cynomolgus tissues, which were mature teratomas, had been engrafted in sheep when more than 1 x 10(6) ES cells were transplanted at <50 gestational days. Despite the sustained engraftment, both cellular and humoral immune responses against the ES cells were detected, and additional transplantation was not successful in the animals. At 2 weeks post-transplantation, the ES cell progeny proliferated when transplanted at 48 (<50) gestational days, whereas they were cleared away when transplanted at 60 (>50) gestational days. These results support the rapid development of the xenogeneic immunological barrier in fetal sheep after 50 gestational days. Notably, a large number of Foxp3(+) regulatory T cells were present around the ES cell progeny, but macrophages were absent when the transplant was conducted at <50 gestational days, implying that regulatory T cells and premature innate immunity might have contributed to the sustained engraftment. In conclusion, long-term macroscopic engraftment of primate ES cells in sheep is feasible despite the xenogeneic immunological barrier.


Journal of Plastic Surgery and Hand Surgery | 2010

Standing nail deformity of the great toes with multiple brachymetacarpia and brachyphalangia of the hand.

Mutsumi Okazaki; Ichiro Shiokawa; Kyoko Sasaki; Rei Watanabe; Kiyonori Harii

Abstract We report the surgical treatment of two patients who had rare complex anomalies of the foot and hand. The nails of their great toes curved dorsally as if they were standing on the nail matrix. They had difficulty in flexing the interphalangeal joint of the great toe. Their hands showed multiple and sporadic brachymetacarpia and brachyphalangia.


Methods of Molecular Biology | 2006

In Vivo Tumor Formation From Primate Embryonic Stem Cells

Takayuki Asano; Kyoko Sasaki; Yoshihiro Kitano; Keiji Terao; Yutaka Hanazono


Transplantation | 2005

Hematopoietic microchimerism in sheep after in utero transplantation of cultured cynomolgus embryonic stem cells.

Kyoko Sasaki; Yoshikazu Nagao; Yoshihiro Kitano; Hideaki Hasegawa; Hiroaki Shibata; Masaaki Takatoku; Satoshi Hayashi; Keiya Ozawa; Yutaka Hanazono


Archive | 2004

METHOD OF DIFFERENTIATION FROM EMBRYO-STEM CELL OF PRIMATE TO HEMATOGENOUS CELL

Yutaka Hanazono; Kyoko Sasaki

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Hiroaki Shibata

National Institutes of Health

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Satoshi Hayashi

Children's Hospital of Philadelphia

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Keiya Ozawa

Jichi Medical University

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Keiji Terao

National Institutes of Health

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