Introduction: Cellular therapy is being discussed as novel therapeutic option for the treatment of neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Cell therapy for ALS currently focuses on the generation of a protective environment for motor neurons instead of cell replacement. Mesenchymal stromal cells (MSC) have already been shown to secrete different growth factors and have anti-apoptotic properties. They therefore appear suitable to create a neuroprotective microenvironment. As they can easily and safely be isolated from human bone marrow, MSC are promising candidates for further preclinical and clinical evaluation. Methods: Human bone marrow derived mesenchymal stromal cells (hMSCs) are isolated by a previously established GMP-conform protocol. In the first study, SOD1G93A transgenic ALS mice (B6.SJL-Tg(SOD1-G93A)1Gur/J) receive intraspinal injections of either hMSCs (bilateral injections of 1x105 cells per side in a volume of 1µl as described), or saline as vehicle control before symptom onset (day 40). In a second study, mice are treated by intraspinal injections before and after symptom onset (day 40 and day 90). One group of animals receives saline on both days, one receives hMSCs at day 40 and saline at day 90 and the third group hMSCs at both days. Possible protective effects of hMSCs are evaluated by survival analysis, measurement of body weight and daily assessment of general condition according to a behavioral score. Motor performance is monitored via rotarod and footprint analysis. Results/Conclusions: The results of our in vivo studies reveal a significant effect of hMSC injections at day 40 on weight loss and on step length (in male animals only) as well as a trend towards increased survival and improvement in general condition and motor performance. Preliminary results of the double injection study show significant effects of repeated intraspinal hMSC injections on motor performance (runtime analysis) and weight loss. Ongoing studies contain histological analyses of spinal cord tissue and further animal studies comparing intraspinal injection and intrathecal injections.