Multipotent progenitor cells are present in human peripheral blood.
To determine whether the peripheral blood in humans contains a population of multipotent progenitor cells (MPCs), products of leukapheresis were obtained from healthy donor volunteers following the administration of granulocyte colony-stimulating factor. Small clusters of adherent proliferating cells were collected, and these cells continued to divide up to 40 population doublings without reaching replicative senescence and growth arrest. MPCs were positive for the transcription factors Nanog, Oct3/4, Sox2, c-Myc, and Klf4 and expressed several antigens characteristic of mesenchymal stem cells. However, they were negative for markers of hematopoietic stem/progenitor cells and bone marrow cell lineages. MPCs had a cloning efficiency of approximately 3%, and following their expansion, retained a highly immature phenotype. Under permissive culture conditions, MPCs differentiated into neurons, glial cells, hepatocytes, cardiomyocytes, endothelial cells, and osteoblasts. Moreover, the gene expression profile of MPCs partially overlapped with that of neural and embryonic stem cells, further demonstrating their primitive, uncommitted phenotype. Following subcutaneous transplantation in nonimmunosuppressed mice, MPCs migrated to distant organs and integrated structurally and functionally within the new tissue, acquiring the identity of resident parenchymal cells. In conclusion, undifferentiated cells with properties of embryonic stem cells can be isolated and expanded from human peripheral blood after granulocyte colony-stimulating factor administration. This cell pool may constitute a unique source of autologous cells with critical clinical import.
Cesselli
Daniela
D
Center for Regenerative Medicine, University of Udine, Italy.
Beltrami
Antonio Paolo
AP
Rigo
Silvia
S
Bergamin
Natascha
N
D'Aurizio
Federica
F
Verardo
Roberto
R
Piazza
Silvano
S
Klaric
Enio
E
Fanin
Renato
R
Toffoletto
Barbara
B
Marzinotto
Stefania
S
Mariuzzi
Laura
L
Finato
Nicoletta
N
Pandolfi
Maura
M
Leri
Annarosa
A
Schneider
Claudio
C
Beltrami
Carlo Alberto
CA
Anversa
Piero
P
D001773:Blood Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D007937:Leukapheresis; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D016179:Granulocyte Colony-Stimulating Factor