Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis

• Published in: The Journal of immunology (1950) 2017-08, Vol.199 (3), p.1069-1085
• Main Authors: Hooshmand, Mitra J, Nguyen, Hal X, Piltti, Katja M, Benavente, Francisca, Hong, Samuel, Flanagan, Lisa, Uchida, Nobuko, Cummings, Brian J, Anderson, Aileen J
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - physiology; Cell adhesion & migration; Cell Differentiation - physiology; Cell Movement; Cells, Cultured; Central nervous system; Complement C1q - antagonists & inhibitors; Complement C1q - biosynthesis; Complement C1q - genetics; Complement C1q - immunology; Complement C3a - antagonists & inhibitors; Complement C3a - biosynthesis; Complement C3a - genetics; Complement C3a - immunology; Complement component C1q; Conditioning; Culture Media, Conditioned; Gliogenesis; Humans; Humoral immunity; Immunity, Innate; Inflammation; Innate immunity; Innate Immunity and Inflammation; Leukocyte migration; Leukocytes (neutrophilic); Leukocytes (polymorphonuclear); Mice; Neural stem cells; Neural Stem Cells - drug effects; Neural Stem Cells - immunology; Neural Stem Cells - physiology; Neurological diseases; Neutrophils - immunology; Neutrophils - metabolism; Proteins; Spinal cord injuries; Spinal Cord Injuries - immunology; Spinal Cord Injuries - physiopathology; Stem cells; Trauma
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1600064

Inflammatory processes play a key role in pathophysiology of many neurologic diseases/trauma, but the effect of immune cells and factors on neurotransplantation strategies remains unclear. We hypothesized that cellular and humoral components of innate immunity alter fate and migration of human neural stem cells (hNSC). In these experiments, conditioned media collected from polymorphonuclear leukocytes (PMN) selectively increased hNSC astrogliogenesis and promoted cell migration in vitro. PMN were shown to generate C1q and C3a; exposure of hNSC to PMN-synthesized concentrations of these complement proteins promoted astrogliogenesis and cell migration. Furthermore, in vitro, Abs directed against C1q and C3a reversed the fate and migration effects observed. In a proof-of-concept in vivo experiment, blockade of C1q and C3a transiently altered hNSC migration and reversed astroglial fate after spinal cord injury. Collectively, these data suggest that modulation of the innate/humoral inflammatory microenvironment may impact the potential of cell-based therapies for recovery and repair following CNS pathology.