- 期刊
Identification of a Candidate Human Neurohematopoietic Stem-Cell Population
並列摘要
It was recently reported that transplantation of clonally derived murine neural stem cells (NSCs) into sublethally irradiated allogeneic hosts lead to a donor-derived hematopoietic reconstitution. The confirmation of the existence of a common neurohematopoietic stem cell in human brain will have a significant impact in stem cell research and in clinical transplantation. In this study, we have investigated if human NSCs possess in vivo hematopoietic potential in SCID-hu mice. Our results demonstrated that human fetal brain tissues contain separate but overlapping EGF-and FGF-2-responsive NSCs. These NSCs derived from human fetal brain tissues express characteristic neural stem/progenitor cell markers including nestin, and receptors for EGF and FGF -2. These human NSCs can be maintained and expanded in vitro for many passages and still retain their self-proliferative and multilineage potential. Results from flow cytometric analyses with CD45 or HLA class 1 antigens demonstrate that cultured human NSCs do not contain any detectable hematopoietic cells. In an in vitro stromal co-culture system optimized for ex vivo expansion of transplantable human hematopoietic stem cells, cultured human NSCs are not able to differentiate into human hematopoietic cells. After transplantation into SCID-hu mice, cultured human NSCs are able to establish a long-term hematopoietic reconstitution in the presence of an intact human bone marrow microenvironment. Our study demonstrates, for the first time, that cultured human NSCs do possess in vivo hematopoietic potential. Furthermore, this study represents the first report to show that differentiation of cultured human NSCs into hematopoietic lineages depends on the presence of an intact human BM microenvironment. The identification of a common human neurohematopoietic stem cell and the cues in the BM microenvironment that direct the neurohematopoietic stem cell to differentiate into hematopoietic lineages will have a significant impact in stem cell research and in clinical transplantation.
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