Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: a new biosafety insight

作者：Flavia Bruna, Anita Plaza, Martha Arango, Iris Espinoza, Paulette A. Conget · 发表于：Stem Cell Research & Therapy · 年份：2018 · DOI：10.1186/s13287-018-0878-1 · 被引用次数：20 · 研究领域：Mesenchymal stem cell research、Biological Research and Disease Studies、Cancer Cells and Metastasis

Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal cells currently tested for multiple therapeutic purposes. Their potential to home into tumors, to secrete trophic/vasculogenic factors, and to suppress immune response raises questions regarding their biosafety. Our aim was to evaluate whether systemically administered allogeneic MSCs modify the natural progression of precancerous lesions and whether their putative effect depends on cancer stage and/or cell dose. Oral squamous cell carcinoma (OSCC) was induced in Syrian golden hamsters by topical application of 7,12-dimethylbenz[a]anthracene in one buccal pouch. At hyperplasia, dysplasia, or papilloma stage, animals received intracardially the vehicle or 0.7 × 10 6 , 7 × 10 6 , or 21 × 10 6 allogeneic bone marrow-derived MSCs/kg. OSCC progression was assessed according to the presence of erythroplakia and leukoplakia, extent of inflammation and vascularization, and appearance, volume, and staging of tumors. Also, the homing of donor cells was studied. Precancerous lesions progressed from hyperplasia to dysplasia in 2 weeks, from dysplasia to papilloma in 3 weeks, and from papilloma to carcinoma in 4 weeks. This time course was unmodified by the systemic administration of MSCs at hyperplasia or dysplasia stages. When MSCs were administered at papilloma stage, lesions did not progress to carcinoma stage. Tumors developed in hamsters receiving 0.7 × 10 6 or 7 × 10 6 MSCs/kg at hyperplasia stage were significantl...