Martino S, Cavalieri C, Emiliani C, Dolcetta D, Cusella De Angelis M G, Chigorno V, Severini G M, Sandhoff K, Bordignon C, Sonnino S, Orlacchio A
Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, University of Perugia, Italy.
Neurochem Res. 2002 Aug;27(7-8):793-800. doi: 10.1023/a:1020256924099.
The therapeutic potential of bone marrow-derived stromal cells for the therapy of Tay-Sachs disease is primarily related to the restoration of their own GM2 ganglioside storage. With this aim, we produced bone marrow-derived stromal cells from the adult Tay-Sachs animal model and transduced them with a retroviral vector encoding for the alpha-subunit of the lysosomal enzyme beta-hexosaminidase A (E.C. 3.2.1.52). Our results demonstrate that transduced Tay-Sachs bone marrow-derived stromal cells have beta-hexosaminidase A comparable to that of bone marrow-derived stromal cells from wild-type mice. Moreover, beta-hexosaminidase A in transduced Tay-Sachs bone marrow-derived stromal cells was able to hydrolyze the GM2 ganglioside in a feeding experiment, thus demonstrating the correction of the altered phenotype.
骨髓源性基质细胞用于治疗泰-萨克斯病的治疗潜力主要与其自身GM2神经节苷脂储存的恢复有关。为此，我们从成年泰-萨克斯病动物模型中制备了骨髓源性基质细胞，并用编码溶酶体酶β-己糖胺酶A（E.C. 3.2.1.52）α亚基的逆转录病毒载体对其进行转导。我们的结果表明，转导后的泰-萨克斯病骨髓源性基质细胞具有与野生型小鼠骨髓源性基质细胞相当的β-己糖胺酶A。此外，在喂养实验中，转导后的泰-萨克斯病骨髓源性基质细胞中的β-己糖胺酶A能够水解GM2神经节苷脂，从而证明了改变的表型得到了纠正。
