Abstract 467: Neural Stem Cells Contribute to Peripheral Nerve Repair by Coordinated Angiogenesis and Neurogenesis
Background: Neural stem cells (NSC) are believed to participate in tissue repair and regeneration after injury. Recent studies have indicated that NSC can differentiate not only into neurons, but also into endothelial cells (EC), suggesting a potentially novel role for NSC in nerve recovery. In the present study, we performed experiments to explore the potential of NSC in the setting of peripheral nerve injury and to test the hypothesis that neurogenesis and vasculogenesis can cooperatively participate in nerve repair.
Methods and results: NSC were isolated from Rosa 26 mice (in which all cells constitutively express b-galactosidase) and expanded ex vivo into neurospheres. Since Estradiol (E2) is known to favorably affect neovascularization after ischemic injury, E2 treatment was used to promote neovascularization. After unilateral sciatic nerve crush injury, C57/BL6 mice were randomized to one of 4 treatments: E2 administered locally via biodegradable polymer Poly Lactide-CO Glycoside (PLGA), NSC administered locally, combination of NSC and E2, or PLGA control. All treatment groups showed significant increases in intraneural angiogenesis and motor conduction velocity (MCV) ratio (P<0.05 vs. cont), with combination of NSC and E2 being the most effective treatment (P<0.05 vs. other groups). Furthermore, NSC treated animals showed higher nerve voltage amplitude (P<0.05 vs. cont and E2) indicating increased neurogenesis. NSC homing was studied in mice injected via tail vein with NSC. Immunostaining of crushed sciatic nerves showed that NSCs migrate to the injury site; moreover some NSC differentiated into EC (CD31 staining) or Schwann cells (S100 staining). Study of NSC differentiation in vitro indicated that NSC can differentiate into multiple lineages, including EC (acLDL, BS-1 lectin, eNOS, CD31 staining), and smooth muscle (α-SM actin) as well as neural lineage. In vitro, E2 promoted NSC differentiation into EC (as acLDL and BS1- lectin double positive cells).
Conclusions: NSC promote angiogenesis and nerve recovery after injury. Both in vivo and in vitro experiments provide evidence that NSC can differentiate into endothelial cells. This study reveals the potential for NSCs to contribute to repair of injured peripheral nerves.