Neural Stem Cell Transplantation Prolongs Survival and Delays Disease Progression in SOD1 Rats

Transplantation with clinical-grade human stem cells delays disease progression, prolongs life and reduces inflammation in SOD1 rats

The hNSCs that were used in this study have been characterised and produced in the Cell Factory of the Santa Maria Hospital in Terni (Italy), which is authorised by AIFA (the Italian Medicine Agency) to produce hNSCs for clinical trials (aM54/2018). The Neurosphere Assay26 is used to isolate, expand and characterise the lines. This method has also been used in the production of cells for phase I trials with Amyotrophic Lateral Sclerosis (NCT0164006723), as well as Secondary Progressive Multiple Sclerosis (NCT03282760).

AIFA has approved the entire process of production, from tissue procurement through to cryopreservation. The hNSCs were obtained after receiving signed informed consent by the mother from foetal tissue that was derived from fetuses who had undergone miscarriage, or died naturally in utero. The hNSCs are plated 48 hours before implantation in the growth medium with a cell density of 10,000/cm2. The day before surgery, hNSCs are collected using centrifugation. Viable cells are counted according to the Trypan blue exclusion criterion, and then the correct number is re-suspended into HBSS.

Three experimental groups of SOD1 transgenic rats were randomly selected: A control group of 9 non-transgenic littermates was used to evaluate the colony’s symptoms. Tacrolimus and cyclosporine are two of the most common immunosuppressive agents used in solid organ transplantation55. They have also been successfully translated into stem cell therapies for PD57. In animal models, both drugs, despite their differences in potency showed excellent survival rates of grafts over many comparative studies58. In our previous studies44,45, we showed that hNSCs could survive in the brain of rats for up to six months without showing signs of rejection, when treated with transient immunosuppression using cyclosporin. Based on these results, we continued the immunosuppressive therapy with cyclosporine (15 mg/kg/day; Sandimmne Novartis), which was started the day after the surgery and continued for 15 more days.


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