Pre-clinical Evaluation of Therapeutic Efficacy of Human Mesenchymal Stromal Cells on Amyotrophic Lateral Sclerosis

Autor: Yi Hsia, 夏熠
Rok vydání: 2016
Druh dokumentu: 學位論文 ; thesis
Popis: 104
Amyotrophic lateral sclerosis(ALS) is a fatal neurodegenerative disease which is caused by the selective loss of motor neurons in the central nervous system. In this study, I injected human mesenchymal stromal cells (hMSCs) into the ALS model mice intravenously at multiple doses to determine the therapeutic effect. Two different transplantation starting timepoints were chosen before and after disease onset. While both transplantation starting timepoints showed prolonged survival time, significantly delayed motor function disorder was only seen for hMSCs injections starting before symptom onset. Furthermore, more larger motor neurons were found and counted from bilateral ventral horns of lumbar spinal cord section in the hMSC treated group than in the sham group. Using anti-human nucleoli antibody, immuonofluorescent stain helped to confirm migration of intravenously-injected cells into the central nervous system, but only a small amount could be detected. The possiblilty of other therapeutic mechanisms of hMSCs could not be excluded. Besides, two proposed mechanisms for ALS, glial cell activity with related inflammatory response and oxidative stress, were investigated. With immunofluorescent stain in the lumbar spinal cord sections for specific markers, GFAP and Nrf2, it was found that positive cells were less in the hMSC treated group than in the only-PBS treated group, and it indicated multiple doses of hMSCs could reduce the level of neuroinflammation and oxidative stress in ALS model mice. In summary, multiple intravenous injections of hMSCs, especially starting before symptom onset, can delay ALS progression in the animal models. The results of this pre-clinical study support further clinical studies of using MSCs.
Databáze: Networked Digital Library of Theses & Dissertations
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