Phenotypic and functional analysis of human fetal liver hematopoietic stem cells in culture

Rollini, Pierre; Faes-Van't Hull, Eveline; Kaiser, Stefan; Kapp, Ursula; Leyvraz, Serge (2007). Phenotypic and functional analysis of human fetal liver hematopoietic stem cells in culture. Stem cells and development, 16(2), pp. 281-96. Larchmont, N.Y.: Mary Ann Liebert 10.1089/scd.2006.0096

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Steady-state hematopoiesis and hematopoietic transplantation rely on the unique potential of stem cells to undergo both self-renewal and multilineage differentiation. Fetal liver (FL) represents a promising alternative source of hematopoietic stem cells (HSCs), but limited by the total cell number obtained in a typical harvest. We reported that human FL nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells (SRCs) could be expanded under simple stroma-free culture conditions. Here, we sought to further characterize FL HSC/SRCs phenotypically and functionally before and following culture. Unexpanded or cultured FL cell suspensions were separated into various subpopulations. These were tested for long-term culture potential and for in vivo repopulating function following transplantation into NOD/SCID mice. We found that upon culture of human FL cells, a tight association between classical stem cell phenotypes, such as CD34(+) /CD38(-) and/or side population, and NOD/SCID repopulating function was lost, as observed with other sources. Although SRC activity before and following culture consistently correlated with the presence of a CD34(+) cell population, we provide evidence that, contrary to umbilical cord blood and adult sources, stem cells present in both CD34(+) and CD34(-) FL populations can sustain long-term hematopoietic cultures. Furthermore, upon additional culture, CD34-depleted cell suspensions, devoid of SRCs, regenerated a population of CD34(+) cells possessing SRC function. Our studies suggest that compared to neonatal and adult sources, the phenotypical characteristics of putative human FL HSCs may be less strictly defined, and reinforce the accumulated evidence that human FL represents a unique, valuable alternative and highly proliferative source of HSCs for clinical applications.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
UniBE Contributor:	Rollini, Pierre
ISSN:	1547-3287
ISBN:	17521239
Publisher:	Mary Ann Liebert
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:52
Last Modified:	05 Dec 2022 14:16
Publisher DOI:	10.1089/scd.2006.0096
PubMed ID:	17521239
Web of Science ID:	000246713800009
URI:	https://boris.unibe.ch/id/eprint/21861 (FactScience: 16460)