Multipotent Progenitor Cells Are Present in Human Peripheral Blood

Abstract

Abstract-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 Ϸ3%, 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.

Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells

“…This step was also necessary to ensure that the cells cultured from both PB and BM had fulfilled the criteria for mesenchymal precursors or stem cells, leaving little doubt that the cells isolated were likely to be MSCs. 12 The implications of this finding are apparent. Future studies using similar techniques must make provisions to ensure that the data, which may demonstrate the presence or absence of CD34 antigens, are appropriately interpreted.…”

“…25 To circumvent this problem, the use of BM mobilization in patients has been described in many literatures. 12,26 This technique involves the stimulation of BM using G-CSF treatment followed by the harvesting of progenitor cells from 1 ml of PB subjected to leukapheresis. This method has inherent limitations which include the low yield obtained following BM mobilization, the non-specific mobilization of mixed type of progenitor cells from BM and, the production of cells which express low MSC-specific gene markers.…”

“…This method has inherent limitations which include the low yield obtained following BM mobilization, the non-specific mobilization of mixed type of progenitor cells from BM and, the production of cells which express low MSC-specific gene markers. 9,12 The long-term consequence of BM stimulation on donors or patients also remains unknown. 26 The report on the success of our ability in isolating MSCs repeatedly from PB would therefore provide greater potential for a wide range of clinical applications, eliminating the need for unwarranted risks to patients while providing an important and easily accessible source of cells for tissue engineering.…”

“…11 In addition, it has also been demonstrated that this technique does not selectively produce MSCs but rather a mix of MSCs, hematopoietic stem cells and, other immature progenitor cells. 12 To ensure that therapeutic applications can be performed using MSCs, a large homogeneous population of cells which can differentiate into specific somatic cells, for example, chondrocytes, may be required. This can be achieved by isolating MSCs from a mixed or heterogenous population of stem cells and expanding their numbers using simple cell culture techniques.…”

Concise Review: Culture Mediated Changes in Fate and/or Potency of Stem Cells

“…The functional differences with MSC (or more mature cell types) and/or embryonic cell types (ESC/EC cells) are also reflected in transcriptome and epigenome studies carried out with MAPC, USSC, MASC, and MPC [43,48,66,69,70]. For example, a transcriptome and epigenetic analysis of human MAPC (hMAPC), human MSC (hMSC), and hEC cells have demonstrated significant differences among the three cell populations [69].…”