Recombinant human megakaryocyte growth and development factor (rHuMGDF), a ligand for c-Mpl, produces functional human platelets in vitro.
Platelet formation, occurring from bone marrow or lung megakaryocytes, has been difficult to study mechanistically. Recombinant human megakaryocyte growth and development factor (rHuMGDF), a recently described cytokine, has now been used to establish an in vitro system in which this important and little understood process occurs. CD34+ cells cultured with rHuMGDF develop into megakaryocytes which form long cytoplasmic extensions (proplatelets) that fragment into platelet-sized particles (in vitro platelets). Morphologically, in vitro and human plasma-derived platelets (control platelets) are virtually identical with respect to size, dense granule distribution and ultrastructural features. Functionally, in vitro and control platelets have similar aggregation and activation responses, and similarly incorporate mepacrine into dense granules. These findings suggest that rHuMGDF is sufficient to generate platelet-synthesizing megakaryocytes from CD34+ cells and provide an experimental setting in which the study of human platelet formation can be adequately performed.
Choi
E S
ES
Amgen Inc., Thousand Oaks, CA 91320, USA.
Hokom
M
M
Bartley
T
T
Li
Y S
YS
Ohashi
H
H
Kato
T
T
Nichol
J L
JL
Skrine
J
J
Knudten
A
A
Chen
J
J
D000244:Adenosine Diphosphate / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D002454:Cell Differentiation; D002478:Cells, Cultured; D005340:Fibrinogen / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis; D011796:Quinacrine / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
D015703:Antigens, CD; D018952:Antigens, CD34; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D013926:Thrombopoietin; D011796:Quinacrine