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Identification of a candidate human neurohematopoietic stem-cell population
1Division of Hematology/Bone Marrow Transplantation, City of Hope National Medical Center, City of Hope, Duarte, CA 91010-3000, USA. cshih@coh.org
Blood
|October 6, 2001
Summary
Human fetal brain contains distinct neural stem cells responsive to epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2). These cells can generate hematopoietic stem cells, impacting stem cell research and transplantation therapies.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Hematopoiesis
Background:
- Previous research indicated murine neurosphere cells could reconstitute hematopoietic function in allogeneic hosts.
- The existence of a common neurohematopoietic stem cell in the human brain has significant implications for stem cell research and clinical transplantation.
Purpose of the Study:
- To investigate the presence and characteristics of neural stem cells in the human fetal brain.
- To determine if human neural stem cells can contribute to hematopoietic reconstitution.
Main Methods:
- Isolation and culture of neurospheres from human fetal brain using epidermal growth factor (EGF) and/or fibroblast growth factor 2 (FGF-2).
- Characterization of neurosphere cells using neural stem/progenitor cell markers.
- Assessment of multipotency for neuronal, astrocyte, and oligodendrocyte differentiation.
- Transplantation of cultured neural stem cells into SCID-hu mice with intact human bone marrow microenvironments.
Main Results:
- Human fetal brain harbors separate but overlapping EGF- and FGF-2-responsive neural stem cells.
- Over 85% of generated neurosphere cells expressed key neural stem/progenitor markers (nestin, EGF receptor, FGF-2 receptor).
- Neural stem cells demonstrated continuous in vitro expansion and multipotency, generating neurons, astrocytes, and oligodendrocytes.
- Transplanted neural stem cells, irrespective of passage number or donor, established long-term hematopoietic reconstitution in SCID-hu mice.
Conclusions:
- Human fetal neural stem cells possess the capacity for hematopoietic reconstitution.
- These findings support the existence of neurohematopoietic stem cells in the human brain.
- This discovery holds potential for advancing stem cell therapies and regenerative medicine.