Production of monocytic cells from bone marrow stem cells: therapeutic usage in Alzheimer’s disease

• Published in: Journal of cellular and molecular medicine Vol. 16; no. 5; pp. 1060 - 1073
• Main Authors: Magga, Johanna, Savchenko, Ekaterina, Malm, Tarja, Rolova, Taisia, Pollari, Eveliina, Valonen, Piia, Lehtonen, Šárka, Jantunen, Esa, Aarnio, Jussi, Lehenkari, Petri, Koistinaho, Milla, Muona, Anu, Koistinaho, Jari
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2012; John Wiley & Sons, Inc
• Subjects: Alzheimer Disease - therapy; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animal models; Animals; Bone marrow; Brain research; Cell culture; Cell differentiation; Cell Separation; Colony-stimulating factor; Cytokines; Cytokines - biosynthesis; Disease Models, Animal; Enzymes; Gene expression; Gene Expression Profiling; Green fluorescent protein; haematopoietic stem cells; Hematopoietic stem cells; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Humans; Inflammation; Macrophage Colony-Stimulating Factor - pharmacology; Macrophages; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Monocytes; Monocytes - drug effects; Monocytes - physiology; Monocytes - transplantation; Neurodegenerative diseases; Original; Peptides; Peripheral blood; Phagocytes; phagocytosis; Phagocytosis - drug effects; Proteins; R&D; Recruitment; Research & development; Stem cells; Therapeutic applications; Transgenic mice; Tumor necrosis factor-TNF; viral transduction; β-Amyloid; United Kingdom > UK; United States > US
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/j.1582-4934.2011.01390.x

Accumulation of amyloid β (Aβ) is a major hallmark in Alzheimer’s disease (AD). Bone marrow derived monocytic cells (BMM) have been shown to reduce Aβ burden in mouse models of AD, alleviating the AD pathology. BMM have been shown to be more efficient phagocytes in AD than the endogenous brain microglia. Because BMM have a natural tendency to infiltrate into the injured area, they could be regarded as optimal candidates for cell‐based therapy in AD. In this study, we describe a method to obtain monocytic cells from BM‐derived haematopoietic stem cells (HSC). Mouse or human HSC were isolated and differentiated in the presence of macrophage colony stimulating factor (MCSF). The cells were characterized by assessing the expression profile of monocyte markers and cytokine response to inflammatory stimulus. The phagocytic capacity was determined with Aβ uptake assay in vitro and Aβ degradation assay of natively formed Aβ deposits ex vivo and in a transgenic APdE9 mouse model of AD in vivo. HSC were lentivirally transduced with enhanced green fluorescent protein (eGFP) to determine the effect of gene modification on the potential of HSC‐derived cells for therapeutic purposes. HSC‐derived monocytic cells (HSCM) displayed inflammatory responses comparable to microglia and peripheral monocytes. We also show that HSCM contributed to Aβ reduction and could be genetically modified without compromising their function. These monocytic cells could be obtained from human BM or mobilized peripheral blood HSC, indicating a potential therapeutic relevance for AD.