Short Article
Mari Paz Quesada, David Garc&i
Abstract
Objective: Mesenchymal stromal cells (MSCs) have powerful immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases leading to significant clinical improvements. The regulatory guidelines specify the need for preclinical studies before any clinical trial, including bio-distribution tests and the exclusion of tumorigenesis. We conducted a preclinical study of human bone marrow MSCs (hBM-MSC) injected intrathecally into immunosuppressed NOD / SCID mice, to explore cellular biodistribution and toxicity as the preferred method of administration for cell therapy in Friedreich's ataxia (FRDA). Methods: To this end, hBM-MSCs were characterized according to ISCT standards and 3 × 105 cells were injected intrathecally into 12 animals (experimental group) and the same volume of culture medium in 6 animals (control group) . Blood samples were taken 24 hours (n = 9) or 4 months (n = 9) to assess toxicity, and eight organs were taken for histological studies. Genomic DNA was isolated from all tissues, and the mouse GAPDH and β2M and human β-actin genes were amplified by qPCR to analyze the biodistribution of hBMMSC. Results: There were no deaths or acute or chronic toxicity. Hematology, biochemistry and body weight were within the range of normal values in all groups. At 24 hours, hBM-MSC were detected in 4/6 vertebral cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumors were found. Conclusion: This study demonstrated that the intrathecal injection of hBM-MSC is safe, non-toxic and does not produce tumors. These results provide additional evidence that hBM-MSC could be used in a clinical trial in patients with FRDA.