Interactions between human adipose stromal cells and mouse neural stem cells in vitro.

Transplantation of adult mesenchymal stem cells (MSCs) into adult rat brain has been known to reduce functional deficits associated with stroke and traumatic brain injury. However, in injured brains, there is no evidence that transplanted MSCs replace lost host brain tissue. In this study, we determined in vitro interaction between human adipose tissue stromal cells (hATSCs), a kind of MSC, and neural stem cells (NSCs). hATSCs were isolated and proliferated from human adipose tissues, and NSCs from the subventricular zone of postnatal mice. When NSCs were cultured on mitomycin-treated hATSC monolayers, their proliferation was decreased, but neuronal differentiation was significantly induced. The percentage of neurons significantly increased in 7 days in cultures of NSCs on hATSCs feeder as compared to NSCs cultured on laminin-coated dishes. When the duration of the cultures was extended to 14 days, hATSCs supported the survival of neurons derived from NSCs. To determine the role of soluble factors from hATSCs, NSCs were cultured with hATSCs conditioned medium or co-cultured with permeable filter on which hATSCs were grown. Although proliferation of NSCs significantly decreased and glial differentiation increased under these experimental conditions, their neuronal differentiation was not affected, indicating that direct physical contact between hATSCs and NSCs is required for induction of neuronal differentiation. These data indicate that hATSCs may provide supportive roles on endogenous neural stem cells, when they are transplanted into damaged brain.