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

ABSTRACT: 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 ×?106, 7 ×?106, or 21?×?106 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 ×?106 or 7?×?106 MSCs/kg at hyperplasia stage were significantly smaller than those found in control animals (25?±?4 or 23?±?4 mm3 versus 72?±?19 mm3, p?

SUBMITTER: Bruna F 

PROVIDER: S-EPMC5948822 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other