Characterization of Mesenchymal Stem Cells in Mucolipidosis Type Ii (i-Cell Disease)

Abstract

Mucolipidosis type II (ML-II, I-cell disease) is a fatal inherited lysosomal storage disease caused by a deficiency of theenzyme N-acetylglucosamine-1-phosphotransferase. A characteristic skeletal phenotype is one of the many clinical manifestationsof ML-II. Since the mechanisms underlying these skeletal defects in ML-II are not completely understood, we hypothesized that adefect in osteogenic differentiation of ML-II bone marrow mesenchymal stem cells (BM-MSCs) might be responsible for this skeletalphenotype. Here, we assessed and characterized the cellular phenotype of BM-MSCs from a ML-II patient before (BBMT) and afterBM transplantation (ABMT), and we compared the results with BM-MSCs from a carrier and a healthy donor. Morphologically, wedid not observe differences in ML-II BBMT and ABMT or carrier MSCs in terms of size or granularity. Osteogenic differentiation wasnot markedly affected by disease or carrier status. Adipogenic differentiation was increased in BBMT ML-II MSCs, but chondrogenicdifferentiation was decreased in both BBMT and ABMT ML-II MSCs. Immunophenotypically no significant differences were observedbetween the samples. Interestingly, the proliferative capacity of BBMT and ABMT ML-II MSCs was increased in comparison to MSCsfrom age-matched healthy donors. These data suggest that MSCs are not likely to cause the skeletal phenotype observed in ML-II, butthey may contribute to the pathogenesis of ML-II as a result of lysosomal storage-induced pathology.