Thèse (M.Sc.)--Université Laval, 2007. / Bibliogr.: f. 77-83. Publié aussi en version électronique dans la Collection Mémoires et thèses électroniques.

Freiburg, Univ., Diss., 2000.

Konstanz, Univ., Diss., 2006.

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Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of the transcription factors OCT4, SOX2, KLF4, and c-Myc holds great promise for the development of personalized cell replacement therapies. In an attempt to minimize the risk of chromosomal disruption and to simplify reprogramming, several studies demonstrated that a reduced set of reprogramming factors is sufficient to generate iPSC. We recently showed that a reduction of reprogramming factors in murine cells not only reduces reprogramming efficiency but also may worsen subsequent differentiation. To prove whether this is also true for human cells, we compared the efficiency of neuronal differentiation of iPSC generated from fetal human neural stem cells with either one (OCT4; hiPSC1F-NSC) or two (OCT4, KLF4; hiPSC2F-NSC) reprogramming factors with iPSC produced from human fibroblasts using three (hiPSC3F-FIB) or four reprogramming factors (hiPSC4F-FIB). After four weeks of coculture with PA6 stromal cells, neuronal differentiation of hiPSC1F-NSC and hiPSC2F-NSC was as efficient as iPSC3F-FIB or iPSC4F-FIB. We conclude that a reduction of reprogramming factors in human cells does reduce reprogramming efficiency but does not alter subsequent differentiation into neural lineages. This is of importance for the development of future application of iPSC in cell replacement therapies.

Ce projet visait à 1) déterminer, chez des personnes en santé et des personnes ayant subi un accident vasculaire cérébral (AVC), la fidélité test-retest des paramètres associés aux stimulations magnétiques transcrâniennes (TMS) et 2) décrire la modulation de l’excitabilité corticospinale reliée au tibial antérieur (TA) à l’aide des TMS ainsi que sa relation avec des mesures cliniques de récupération locomotrice. Les paramètres démontrant une fidélité acceptable chez les deux groupes de participants étaient le seuil moteur, le plateau et la valeur maximale des réponses motrices évoquées et la période de silence maximale. Une réorganisation cérébrale a été observée au stade aigu post-AVC: durant la période de réadaptation active, l’hyperexcitablilité de l’hémisphère non lésé s’est résorbée et l’excitabilité de l’hémisphère lésé a augmentée, suggérant un meilleur contrôle contralatéral du TA parétique. Parallèlement, une augmentation de la vitesse de marche a été documentée suggérant un lien entre le contrôle contralatéral et la récupération fonctionnelle. / The project aimed to 1) determine, in healthy subjects and persons with chronic stroke, the test-retest reliability of outcome measures related to transcranial magnetic stimulations (TMS) and 2) describe, by means of TMS, the modulation of the corticospinal excitability of the tibialis anterior (TA) as well as test its relationship with clinical measures of locomotor recovery. The TMS outcome measures presenting acceptable reliability level in both groups of participants were the motor threshold, the plateau and maximal values of the motor evoked potentials and the maximal silent period. Cerebral reorganization was observed in the acute stage post-stroke: during the active rehabilitation period, the non lesioned hemisphere’s hyperexcitability decreased and there was a gradual increase of the lesioned hemisphere’s excitability, suggesting a greater control of the paretic TA via the contralateral tracts. A parallel increase in gait speed was also documented thus suggesting a link between a contralateral control and functional recovery.

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