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(Circulation Research. 2009;104:1225.)
© 2009 American Heart Association, Inc.

Clinical Research

Multipotent Progenitor Cells Are Present in Human Peripheral Blood

Daniela Cesselli, Antonio Paolo Beltrami, Silvia Rigo, Natascha Bergamin, Federica D'Aurizio, Roberto Verardo, Silvano Piazza, Enio Klaric, Renato Fanin, Barbara Toffoletto, Stefania Marzinotto, Laura Mariuzzi, Nicoletta Finato, Maura Pandolfi, Annarosa Leri, Claudio Schneider, Carlo Alberto Beltrami, Piero Anversa

From the Center for Regenerative Medicine (D.C., A.P.B., S.R., N.B., F.D., R.F., B.T., S.M., L.M., N.F., M.P., C.A.B.), University of Udine, Italy; National Biotechnology Laboratory (R.V., S.P., E.K., C.S.), Padriciano, Trieste, Italy; and Departments of Anesthesia and Medicine (A.L., P.A.), Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Piero Anversa, MD, Departments of Anesthesia and Medicine, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail panversa{at}partners.org

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 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.

Key Words: stem cells • stem cell plasticity • circulating progenitors • multipotency • gene expression profile