Transplantation of neural stem cells that overexpress SOD1 enhances amelioration of intracerebral hemorrhage in mice

Abstract

Previous studies have shown that intraparenchymal transplantation of neural stem cells (NSCs) ameliorates neurological deficits in animals with intracerebral hemorrhage (ICH). However, massive grafted cell death following transplantation, possibly caused by a hostile host brain environment, lessens the effectiveness of this approach. We focused on the effect of oxidative stress induced by hemoglobin against grafted NSCs and showed genetic manipulation to overexpress copper/zinc-superoxide dismutase (SOD1), which is a specific antioxidant enzyme that counteract superoxide anions, enhances survival of grafted NSCs and accelerates amelioration of ICH. Our results suggest that enhanced antioxidative activity in NSCs improves efficacy of stem cell therapy for ICH.

Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice

“…10 In brief, bilateral subventricular zones were dissected and mechanically dissociated. The cells were collected and suspended in Neurobasal-A medium (Invitrogen, Carlsbad, CA, USA) containing B-27 supplement (Invitrogen), L-glutamine (Invitrogen), 20 ng/ml mouse fibroblast growth factor-basic (PeproTech, Rocky Hill, NJ, USA), and 10 ng/ml mouse epidermal growth factor (PeproTech).…”

“…Hemoglobin was prepared as described. 10 Blood was drawn by cardiac puncture and centrifuged at 1250 g for 5 minutes at 4 C. The supernatant was removed and the pellet was washed, resuspended in sterile saline, and lysed by two freeze-thaw cycles. The sample was then centrifuged and the supernatant was removed.…”

“…Studies have shown the neuroprotection of intraparenchymal cell transplants that can ameliorate primary and secondary injury in animals with ICH, as well as enhance functional recovery. [5][6][7][8][9][10][11][12] At the site of neuroprotection, the transplantation should be performed at the acute stage of ICH, because the irreversible brain damage extends as time goes by. However, the hostile host environment during the acute stage of ICH limits the efficacy of this strategy as more than 85% of transplanted cells are no longer present 8 weeks after transplant.…”

“…A potential solution to this problem is to modify the cells prior to transplant to enhance their ability to survive and facilitate functional recovery. [10][11][12] Several reports have shown that preconditioning induced by sublethal hypoxia or ischemia can markedly improve the tolerance of treated subjects to more severe insults. [13][14][15] However, the effect of hypoxic preconditioning on cell transplantation therapy for ICH remains unclear.…”

Effectiveness of muscle basal lamina carrying neural stem cells and olfactory ensheathing cells in spinal cord repair

“…Because NSCs have the potential to differentiate into neurons (Lee et al, 2012), oligodendrocytes, and axons (Decimo et al, 2011;Yasuda et al, 2011) and also have the ability to fill the spinal cord cavity and blend with host spinal cord tissues (Boido et al, 2011;Li et al, 2011), they may be useful for repairing SCI. Animal experiments have indicated that the regenerated axon has limited ability to cross fiber scars to set up new neural pathways because the internal environment of the organism affects the survival and differentiation of NSCs (Lian Jin et al, 2011;Meng et al, 2011;Su et al, 2011;Wang et al, 2011;Wakai et al, 2014). Therefore, limited effects would be observed for the repair using only NSCs.…”