RRC ID 36669
Author Sakashita K, Kato I, Daifu T, Saida S, Hiramatsu H, Nishinaka Y, Ebihara Y, Ma F, Matsuda K, Saito S, Hirabayashi K, Kurata T, Uyen LT, Nakazawa Y, Tsuji K, Heike T, Nakahata T, Koike K.
Title In vitro expansion of CD34(+)CD38(-) cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia.
Journal Leukemia
Abstract Using serum-containing culture, we examined whether AGM-S3 stromal cells, alone or in combination with hematopoietic growth factor(s), stimulated the proliferation of CD34(+) cells from patients with juvenile myelomonocytic leukemia (JMML). AGM-S3 cells in concert with stem cell factor plus thrombopoietin increased the numbers of peripheral blood CD34(+) cells to approximately 20-fold of the input value after 2 weeks in nine JMML patients with either PTPN11 mutations or RAS mutations, who received allogeneic hematopoietic transplantation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) also augmented the proliferation of JMML CD34(+) cells on AGM-S3 cells. The expansion potential of CD34(+) cells was markedly low in four patients who achieved spontaneous hematological improvement. A large proportion of day-14-cultured CD34(+) cells were negative for CD38 and cryopreservable. Cultured JMML CD34(+)CD38(-) cells expressed CD117, CD116, c-mpl, CD123, CD90, but not CXCR4, and formed GM and erythroid colonies. Day-7-cultured CD34(+) cells from two of three JMML patients injected intrafemorally into immunodeficient mice stimulated with human GM-CSF after transplantation displayed significant hematopoietic reconstitution. The abilities of OP9 cells and MS-5 cells were one-third and one-tenth, respectively, of the value obtained with AGM-S3 cells. Our culture system may provide a useful tool for elucidating leukemogenesis and for therapeutic approaches in JMML.
Volume 29(3)
Pages 606-14
Published 2015-3-1
DOI 10.1038/leu.2014.239
PII leu2014239
PMID 25102944
MeSH ADP-ribosyl Cyclase 1 / genetics ADP-ribosyl Cyclase 1 / metabolism Adolescent Animals Antigens, CD34 / genetics Antigens, CD34 / metabolism Cell Proliferation / drug effects Clone Cells Coculture Techniques Embryonic Stem Cells / drug effects* Embryonic Stem Cells / metabolism Embryonic Stem Cells / pathology GTP Phosphohydrolases / genetics GTP Phosphohydrolases / metabolism Gene Expression Regulation, Leukemic* Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology* Hematopoietic Stem Cells / drug effects* Hematopoietic Stem Cells / metabolism Hematopoietic Stem Cells / pathology Humans Leukemia, Myelomonocytic, Juvenile / genetics* Leukemia, Myelomonocytic, Juvenile / metabolism Leukemia, Myelomonocytic, Juvenile / pathology Membrane Proteins / genetics Membrane Proteins / metabolism Mice Mice, Inbred NOD Mice, SCID Mutation Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Neoplastic Stem Cells / transplantation Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins p21(ras) Signal Transduction Stromal Cells / drug effects* Stromal Cells / metabolism Stromal Cells / pathology ras Proteins / genetics ras Proteins / metabolism
IF 8.665
Times Cited 15
Cord blood stem cells for research 研究用ヒト臍帯血幹細胞
Human and Animal Cells OP9(RCB1124)