Biodistribution, Long-term Survival, and Safety of Human Adipose Tissue-derived Mesenchymal Stem Cells Transplanted in Nude Mice by High Sensitivity Non-invasive Bioluminescence Imaging

Abstract

Cultivated murine bone marrow mesenchymal stem cells (MSCs) frequently accumulate chromosome abnormalities, become oncogenically transformed, and generate sarcomas when transplanted in mice. Although human MSCs appear to be more resistant, oncogenic transformation has also been observed in MSCs cultivated past the senescence phase. Cell therapy for tissue regeneration using human autologous MSCs requires transplantation of cells previously expanded in vitro. Thus, an important concern is to determine if oncogenic transformation is a necessary outcome of the expansion procedures. We have analyzed the proliferation capacity, organ colonization, and oncogenicity of enhanced green fluorescent protein and luciferase-labeled human adipose tissue-derived mesenchymal stem cells (hAMSCs), implanted in immunocompromised mice during a prolonged time period (8 months) using a non-invasive bioluminescence imaging procedure. Our data indicates that the liver was the preferred target organ for colonization by intramuscular or intravenous implantation of hAMSCs. The implanted cells tended to maintain a steady state, population did not proliferate rapidly after implantation, and no detectable chromosomal abnormalities nor tumors formed during the 8 months of residence in the host's tissues. It would appear that hAMSCs, contrary to their murine correlatives, could be safe candidates for autologous cell therapy procedures since in our experiments they show undetectable predisposition to oncogenic transformation after cultivation in vitro and implantation in mice.

Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

“…Unlike hNSCs and hMSCs, human adipose tissue-derived stem cells (hADSCs) represent an abundant and easily accessible autologous source of stem cells, with fewer ethical concerns associated with their use. Additionally, unmodified hADSCs remain free of oncogenic transformation for at least 8 mo when injected into immunocompromised mice, demonstrating more oncogenic resistance than human bone marrowderived stem cells (9). Therefore, hADSCs derived from fat tissue could represent a better alternative for stem cell-based cancer gene therapy.…”

Regeneration of Skin Surface by Multipotent Mesenchymal Stem Cells of Adipose Tissue in Laboratory Animals with Infected Wounds

“…MSCs of adipose tissue transplantation has shown great promise in other areas including oncology [40], hepathology [21], orthopedic surgery [35], stroke and neurological diseases, cardiovascular disease, urology [23].…”

Uncultured Autogenous Adipose-derived Regenerative Cells Promote Bone Formation During Distraction Osteogenesis in Rats

“…For example, after intravenous injection, ADSCs were found to persist in mice even after 8 months [24]. In contrast, in other models, in which simple subcutaneous injection was used, ADSCs dissipated after as few as 5 days [26].…”