Embryonic stem and haematopoietic progenitor cells resist to Aβ oligomer toxicity and maintain the differentiation potency in culture

Abstract

Regenerative medicine deals with the possible use of stem cells to repair tissues damaged by aging and related diseases, including amyloidoses. In the latter case, the toxicity of the amyloid deposits can, in principle, question the possibility to graft specific tissues by undifferentiated cells. To assess whether stem cells are vulnerable to amyloid toxicity, we exposed, in culture, murine embryonic stem (ES) cells and haematopoietic progenitor (HP) cells to oligomers of the amyloidogenic peptide Aβ42 at concentrations previously shown to be cytotoxic to several other cell types. These stem cells did not display any sign of apoptosis and their survival, proliferation and differentiation were not affected by the oligomers although the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed that ES, but not HP, cells displayed some impaired ability to reduce the tetrazole salts possibly as a result of transient oxidative stress. Our results support a remarkable resistance of the investigated stem cells against amyloids and hence their potential use in cell therapy of Alzheimer's disease and, possibly, other amyloid diseases.

Keywords:

• Amyloid oligomer toxicity
• stem cells
• cell therapy

Abbreviations
TEM	=	transmission electron microscopy
ES	=	murine embryonic stem cells
HP	=	haematopoietic progenitor cells
MTT	=	3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
AFM	=	atomic force microscopy
LDPBC	=	light density peripheral blood cells
LDH	=	lactate dehydrogenase
PI	=	propidium iodide

Abbreviations
TEM	=	transmission electron microscopy
ES	=	murine embryonic stem cells
HP	=	haematopoietic progenitor cells
MTT	=	3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
AFM	=	atomic force microscopy
LDPBC	=	light density peripheral blood cells
LDH	=	lactate dehydrogenase
PI	=	propidium iodide

Acknowledgements

This work was supported by: the Italian MIUR (FIRB Project N. RBIP06FH7J, PRIN Project N. 2007XY59ZJ), Fondazione CARIPLO (Projects 2007.5151and 2009-2543), UNIPV-Regione Lombardia (Project on Material Science and Biomedicine), Fondazione I.R.C.C.S. Policlinico San Matteo, Millipore.