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  • Title: Multiple administrations of human marrow stromal cells through cerebrospinal fluid prolong survival in a transgenic mouse model of amyotrophic lateral sclerosis.
    Author: Zhang C, Zhou C, Teng JJ, Zhao RL, Song YQ, Zhang C.
    Journal: Cytotherapy; 2009; 11(3):299-306. PubMed ID: 19333801.
    Abstract:
    BACKGROUND AIMS: The blood-brain barrier (BBB) is the main obstacle to cell therapy for neurologic disorders such as amyotrophic lateral sclerosis (ALS). Intrathecal injection is a potential method for cell transplantation because it would bypass the BBB. We investigated the effects of human marrow stromal cells (hMSC) delivered through cerebrospinal fluid (CSF) in a transgenic mouse model of ALS. METHODS: 5 x 10(5) hMSC were delivered into the CSF of SOD1 transgenic mice at the age of 8 weeks (single transplantation group) or 8, 10 and 12 weeks (multiple transplantation group). Clinical observation, weight, hanging wire test and motor neuron count were used to assess the disease progression in the SOD1 mice. Immunohistochemistry was performed with human-specific antibody against HuNu to examine the distribution of hMSC in the lumbar spinal cord parenchyma of SOD1 mice at the age of 15 weeks. RESULTS: Single transplantation of hMSC did not have a beneficial effect in SOD1 mice. Multiple transplantations of hMSC attenuated weight loss, enhanced motor performance, decreased motor neuron loss and, importantly, increased survival in SOD1 transgenic mice. However, only a few hMSC delivered through the CSF migrated into the lumbar spinal cord parenchyma of SOD1 mice. CONCLUSIONS: Multiple administrations of hMSC through CSF may have a therapeutic effect in SOD1 mice, although limited numbers of cells migrate into the lumbar spinal cord parenchyma. It is likely that the hMSC remaining in CSF are responsible for the effect in SOD1 mice.
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