Restoration of function by replacement of spinal cord segments in the rat

Abstract

Reconstruction of a severed mammalian spinal cord with restoration of function has so far not been achieved, although structural and functional restitution after spinal transection has been successful in some lower vertebrates. In quail-chick and chick-chick chimaeras, spinal cord segments were found to be functional after replacement by isotopic and isochronic grafting of the neural tube. Here we achieve such a replacement in neonatal rats under less restricted topological and temporal conditions than were necessary for the avian chimaeras. The replaced segments united with the host spinal cord and promoted robust growth and regrowth of axons across the graft, enabling neural connections to be reconstructed that were hardly distinguishable from normal. The animals with replaced segments could walk, run and climb with almost normal hind-forelimb coordination. This functional restoration in these animals appeared to be permanent, raising the possibility of therapeutic application in humans.

Dopaminergic microtransplants into the substantia nigra of neonatal rats with bilateral 6-OHDA lesions. I. Evidence for anatomical reconstruction of the nigrostriatal pathway

“…In particular, highly organized and specific axonal projections have been demonstrated from grafts of fetal cortex implanted into the cerebral cortex (Floeter and Jones, 1984;Castro et al, 1985;Stanfield and O'Leary, 198.5;Hefner et al, 1990), from grafts of hippocampal neurons in the hippocampus (Sunde et al, 1984;Zimmer et al, 1987) and for retinal ganglion cells in the retinotectal system Lund, 1987, 1990;Lund et al, 1988) in neonatal recipients. A similar developmental plasticity has been demonstrated for fetal spinal cord grafts implanted into the neonatally lesioned spinal cord associated with signs of functional restoration (Iwashita et al, 1994).…”

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

“…Among these strategies, cell transplantation is at present considered to be the most effective way of repairing SCIs. 1 So far, several different kinds of cells have been used as transplants for spinal cord regeneration, including Schwann cells, 2 embryonic spinal cord stem cells, 3 olfactory ensheathing cells, 4 macrophages, 5 choroids plexus ependymal cells, 6 neural stem cells 7 and bone marrow stromal cells. 1 SCI does not need to be cured completely for function to return.…”

Freeze-dried poly(d,l-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord

“…One approach to promote axonal regeneration in the injured spinal cord, which has been investigated extensively, is the grafting of three-dimensional cellular transplants bridging the injury gap or cyst (e.g., Schwann cells, peripheral nerves; olfactory ensheathing cells; reviewed by [6][7][8]). Many of these repair strategies limit spinal tissue loss [9,10], promote regeneration/ sparing of spinal and supraspinal axons [9][10][11][12][13], and result in some functional recovery [9][10][11][12][13][14][15][16][17][18]. Due to the ongoing (secondary) tissue loss following an injury, it seems inevitable that repair of the (sub-) chronically injured cord will require strategies that include the transplantation of cellular grafts to replace lost spinal nervous tissue.…”