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Florence PERRIN"Grafted Human Embryonic Progenitors Expressing Neurogenin-2 in a rat model of spinal cord injury"

Abstract :

Spinal cord injury often induces irreversible lesions leading to para-or tetraplegia.
Even if possible, axonal regeneration in the central nervous system does not occur spontaneously. The absence of spontaneous regeneration is thus due to a non-permissive environment and not to an intrinsic inability of neurons to re-growth. Transplantation in the injured spinal cord of stem cells or progenitor cells derived from these cells has long been considered as a therapeutic strategy for spinal cord repair, with the final aim of reducing or even reversing symptoms. Within a European consortium, we applied a strategy of cell transplantation in a rat model of severe spinal compression. We have grafted human neural progenitors that, for some them, had been genetically modified to express Neurogenin 2 (Ngn2). Human neural progenitor transduced to express Ngn2 transplantation in our model of spinal cord compression leads to an increase in functional recovery. Transient Ngn2 expression is sufficient, this point is important for the development of a protocol in humans. This improvement is not correlated to a modification in lesion extension and only 10% of intact fibers are sufficient for motor function. After transplantation of Ngn2 expressing cells, the partial restoration of the density of serotonergic fibers and localization of one of its receptors in the spinal cord below the lesion is correlated with improved functional recovery. One month after transplantation, no cells are found in the spinal cord parenchyma, the functional gain observed is thus not due to a cell replacement but probably to a greater trophic support caused or induced by the transplanted cells. Moreover, animals grafted with naive cells (not expressing Ngn2) presented a worse functional recovery than the non-grafted group. This is important given the current clinical enthusiasm for the use of stem cells.

Selected publications

N. Lonjon, G. Boniface, R. Feifel, R. Endres, M. Giménez y Ribotta, A. Privat and F.E. Perrin.
Potential adverse effects of Cyclosporin A on Kidneys after Spinal Cord Injuries.
Spinal Cord, 49(3):472-9.
F.E. Perrin.
Greffer pour régénérer (transplantation for regeneration).
Biofutur 332 : 46-49.

F.E. Perrin, Y. Gerber, G. Boniface, M. Teigel, L. Bauchet, and A. Privat.
Anatomical study of serotoninergic innervation and 5HT1A receptors in human spinal cord.
Cell Death and Disease. 2:e218.

D. Mamaeva, C. Ripoll, C. Bony, F.E. Perrin, M. Teigell, I. Bieche, R. Lidereau, A. Privat, V.e Rigau, H. Guillon, D. Noel, L. Bauchet and J. P. Hugnot.
Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord.
BMC Neuroscience. 10;12(1):99.

Sandrine Bertrand