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Umbilical cord blood stem cells can expand hematopoietic and neuroglial progenitors in vitro

Lookup NU author(s): Professor Colin McGuckin, Dr Nicolas Forraz

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Abstract

The ability of hematopoietic tissue-derived adult stem cells to transdifferentiate into neural progenitor cells offers an interesting alternative to central nervous system (CNS)- or embryonic-derived stem cells as a viable source for cellular therapies applied to brain regeneration. Umbilical cord blood (CB) due to its primitive nature and it unproblematic collection appears as a promising candidate for multipotent stem cell harvest. We developed a negative immunomagnetic selection method that depletes CB from hematopoietic lineage marker-expressing cells, hence isolating a discrete lineage negative (LinNeg) stem cell population (0.1% of CB mononucleated cell [MCN] population). In liquid culture supplemented with thrombopoietin, flt-3 ligand, and c-kit ligand (TPOFLK), CB LinNeg stem cells could expand primitive nonadherent hematopoietic progenitors (up to 47-fold) and simultaneously produce slow-dividing adherent cells with neuroglial progenitor cell morphology over 8 weeks. Laser scanning confocal microscopy analysis identified these adherent cells to express glial fibrillary acidic protein (GFAP). Gene expression analysis showed upregulation of primitive neuroglial progenitor cell markers including, GFAP, nestin, musashi-1, and necdin. ELISA quantification of liquid culture supernatant revealed the in vitro release of transforming growth factor beta-1 (TGFbeta1), glial cell line-derived neurotrophic factor (GDNF) suggesting their contribution to CB LinNeg stem cell transdifferentiation into neuroglial progenitors. Our study supports that a single CB specimen can be pre-expanded in TPOFLK to produce both primitive hematopoietic and neuropoietic progenitors, hence widening CB clinical potential for cellular therapies.

Publication metadata

Author(s): McGuckin CP, Forraz N, Allouard Q, Pettengell R

Publication type: Article

Publication status: Published

Journal: Experimental Cell Research

Year: 2004

Volume: 295

Issue: 2

Pages: 350-359

Print publication date: 25/02/2004

ISSN (print): 0014-4827

ISSN (electronic): 1090-2422

Publisher: Academic Press

URL: http://dx.doi.org/10.1016/j.yexcr.2003.12.028

DOI: 10.1016/j.yexcr.2003.12.028

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