TY - JOUR
T1 - Generation of induced pluripotent stem cells derived from primary and secondary myelofibrosis patient samples
AU - Hosoi, Masataka
AU - Kumano, Keiki
AU - Taoka, Kazuki
AU - Arai, Shunya
AU - Kataoka, Keisuke
AU - Ueda, Koki
AU - Kamikubo, Yasuhiko
AU - Takayama, Naoya
AU - Otsu, Makoto
AU - Eto, Koji
AU - Nakauchi, Hiromitsu
AU - Kurokawa, Mineo
N1 - Funding Information:
We thank K. Tsuji for special advice with experience, and Y. Hokama and Y. Izawa for technical assistance with experiments. Thrombopoietin receptor agonists rHuMGDF and rHuEPO were a kind gift from Kyowa Hakko Kirin. This work was supported by a grant-in-aid from Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan, and the Tokyo Biochemical Research Foundation , Tokyo, Japan.
Publisher Copyright:
© 2014 ISEH - International Society for Experimental Hematology.
PY - 2014
Y1 - 2014
N2 - Induced pluripotent stem cells (iPS) derived from disease cells are expected to provide a new experimental material, especially for diseases from which samples are difficult to obtain. In this study, we generated iPS from samples from patients with primary and secondary myelofibrosis. The primary myelofibrosis cells had chromosome 13q deletions, and the secondary myelofibrosis (SMF) cells had JAK2V617F mutations. The myelofibrosis patient cell-derived iPS (MF-iPS) were confirmed as possessing these parental disease-specific genomic markers. The capacity to form three germ layers was confirmed by teratoma assay. By co-culture with specific feeder cells and cytokines, MF-iPS can re-differentiate into blood progenitor cells and finally into megakaryocytes. We found that mRNA levels of interleukin. -8, one of the candidate cytokines related to the pathogenesis of myelofibrosis, was elevated predominantly in megakaryocytes derived from MF-iPS. Because megakaryocytes from myelofibrosis clones are considered to produce critical mediators to proliferate fibroblasts in the bone marrow and iPS can provide differentiated cells abundantly, the disease-specific iPS we established should be a good research tool for this intractable disease.
AB - Induced pluripotent stem cells (iPS) derived from disease cells are expected to provide a new experimental material, especially for diseases from which samples are difficult to obtain. In this study, we generated iPS from samples from patients with primary and secondary myelofibrosis. The primary myelofibrosis cells had chromosome 13q deletions, and the secondary myelofibrosis (SMF) cells had JAK2V617F mutations. The myelofibrosis patient cell-derived iPS (MF-iPS) were confirmed as possessing these parental disease-specific genomic markers. The capacity to form three germ layers was confirmed by teratoma assay. By co-culture with specific feeder cells and cytokines, MF-iPS can re-differentiate into blood progenitor cells and finally into megakaryocytes. We found that mRNA levels of interleukin. -8, one of the candidate cytokines related to the pathogenesis of myelofibrosis, was elevated predominantly in megakaryocytes derived from MF-iPS. Because megakaryocytes from myelofibrosis clones are considered to produce critical mediators to proliferate fibroblasts in the bone marrow and iPS can provide differentiated cells abundantly, the disease-specific iPS we established should be a good research tool for this intractable disease.
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U2 - 10.1016/j.exphem.2014.03.010
DO - 10.1016/j.exphem.2014.03.010
M3 - Article
C2 - 24859480
AN - SCOPUS:84908599033
SN - 0301-472X
VL - 42
SP - 816
EP - 825
JO - Experimental Hematology
JF - Experimental Hematology
IS - 9
ER -
