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

Abstract

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.

Live-cell time-lapse imaging and single-cell tracking of in vitro cultured neural stem cells – Tools for analyzing dynamics of cell cycle, migration, and lineage selection

“…In comparison to rodent cells, hNSC require a longer time for in vitro differentiation. Our previous data suggest that a small proportion of hNSC remain uncommitted even after a 14 day in vitro differentiation period [15], however, evaluation of GFAP + cells in combination of stem cell markers Sox2 and Nestin indicates that by this timepoint GFAP expression correlates with astroglial lineage commitment rather than maintenance of neural progenitors [6]. After the last image acquisition at the 14 day timepoint, cells were fixed and triple-immunostained for lineage characterization using astroglial marker GFAP, oligodendroglial maker nuclear Olig2, or neuronal marker Map2 (Fig.…”

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

“…Astrocytes have a variety of functions, including formation and maintenance of neuronal synapses and the blood–brain barrier. However, many NS/PCs present in damaged CNS tissue differentiate into reactive astrocytes, which create a glial scar and, when in excess, likely contribute to a chronic inflammatory environment thought to prevent regeneration …”

“…However, many NS/PCs present in damaged CNS tissue differentiate into reactive astrocytes, which create a glial scar and, when in excess, likely contribute to a chronic inflammatory environment thought to prevent regeneration. [4][5][6][7][8][9][10] Over the past two decades, many studies have evaluated the therapeutic potential of transplanting human NS/PCs or oligodendrocyte progenitor cells (OPCs), the intermediary progenitors between NS/PCs and mature oligodendrocytes ( Fig. 1), to regenerate CNS tissues after injury.…”

Pathological significance of C3aR signaling in the tumor cells of clear cell renal cell carcinoma: a clinical observation

“…However, increasing evidence from the last two decades has demonstrated that C3aR is also expressed by many non-immune cells and participates in various physiological and pathological processes. For examples, C3aR signaling was reported to participate in the regulation of eye morphogenesis [16], neural development [17][18], embryonic chick retina [19] and cardiac resident cell [20] regeneration, astroglial cell differentiation [21] and survival [22], diet-induced obesity and metabolic dysfunction [23], and tau hyperphosphorylation in Alzheimer's Disease [24]. Also, C3aR signaling was found to be involved in the induction of in ammatory cytokines [25], proliferation of mesangial [11] and carcinoma cells [12] and EMT of tubular epithelial cells [10].…”