Neuroectodermal differentiation from mouse multipotent adult progenitor cells

^*Stem Cell Institute and Division of Hematology, Department of Medicine, and ^†Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455

Abstract

We recently showed that a rare cell from murine bone marrow, which we termed multipotent adult progenitor cells (MAPCs), can be expanded for >120 population doublings. Mouse (m)MAPCs differentiate into mesenchymal lineage cells as well as endothelium and endoderm, and, when injected in the blastocyst, mMAPCs contribute to most if not all somatic cell lineages including the different cell types of the brain. Our results, reported herein, demonstrate that mMAPCs can also be induced to differentiate into cells having anatomical and electrophysiological characteristics similar to those of midbrain neurons. Differentiation to a neuronal phenotype was achieved by coculturing mMAPCs with astrocytes, suggesting that neuronal differentiation may require astrocyte-derived factors similar to what is required for the differentiation of embryonic stem cells and neural stem cells to neurons. Differentiation of mMAPCs to neuron-like cells follows similar developmental steps as described for embryonic stem cells and neural stem cells. MAPCs therefore may constitute a source of cells for treatment of central nervous system disorders.

Footnotes

↵ ‡ To whom correspondence should be addressed at: University of Minnesota, MMC 716, 422 Delaware Street SE, Minneapolis, MN 55455. E-mail: verfa001{at}umn.edu.
This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Regenerative Medicine,” held October 18-22, 2002, at the Arnold and Mabel Beckman Center of the National Academies of Science and Engineering in Irvine, CA.
Abbreviations: BM, bone marrow; NSC, neural stem cell; MAPC, multipotent adult progenitor cell; m, mouse; ES, embryonic stem; FGF, fibroblast growth factor; bFGF, basic FGF; SHH, Sonic Hedgehog; BDNF, brain-derived neurotrophic factor; En, embryonic day n; NF, neurofilament; MBP, myelin basic protein; TH, tyrosine hydroxylase; DDC, dopa-decarboxylase; TrH, tryptophan hydroxylase; GABA, γ-aminobutyric acid; GFAP, glial fibrillary acidic protein; TTX, tetrodotoxin; PDGF, platelet-derived growth factor; eGFP, enhanced GFP.