Efficient assay for evaluating human thrombopoiesis using NOD/SCID mice transplanted with cord blood CD34+ cells.
A suitable model for the preclinical study of human platelet production in vivo has not been available. NOD/SCID mice were characterized as representing an efficient engraftment model for human hematopoietic stem cells, which resulted in the production of human platelets. Here, we evaluated in vivo human thrombopoiesis and ex vivo human platelet functions in NOD/SCID mice transplanted with human cord blood (CB) CD34(+) cells. Human platelets and human CD45(+) cells appeared in peripheral blood of NOD/SCID mice from 4 wk after transplantation. Human platelets produced in these mice showed CD62P expression and the activation of GPIIb/IIIa on human platelets on stimulation with an agonist. PEG-rHuMGDF (0, 0.5 and 5 microg/kg/d s.c.) was injected for 14 d into mice that had been confirmed to produce human platelets stably. The number of human platelets increased about twofold at 0.5 microg/kg/d and about fivefold at 5 microg/kg/d after 14 d. Withdrawal of PEG-rHuMGDF administration caused the human platelet count to return to the pretreatment level. Further, re-administration of PEG-rHuMGDF induced a similar human thrombopoietic response as it did on initial administration. These results suggest that NOD/SCID mice engrafted with human CB CD34(+) cells will be useful for the study of human platelet production in vivo.
Suzuki
Ken-ichi
K
Department of Pediatrics, Kyoto University, Kyoto, Japan.
Hiramatsu
Hidefumi
H
Fukushima-Shintani
Mari
M
Heike
Toshio
T
Nakahata
Tatsutoshi
T
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001681:Biological Assay / Q000379:methods*; D001792:Blood Platelets / Q000737:chemistry; D003114:Colony-Forming Units Assay / Q000379:methods*; D036101:Cord Blood Stem Cell Transplantation; D006801:Humans; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000032:analysis; D008533:Megakaryocytes / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019007:P-Selectin / Q000032:analysis; D015539:Platelet Activation / Q000187:drug effects; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D034061:Thrombopoiesis / Q000187:drug effects; D013926:Thrombopoietin / Q000494:pharmacology; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; D019007:P-Selectin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human