Multipotent mesenchymal stromal cells (MSCs) play an important role in stromal support for hematopoietic stem cells, immune modulation, and tissue regeneration. We investigated their potential as cellular therapeutic tools in neurometabolic diseases as a growing number of affected children undergo to
bone marrow transplantation. MSCs were isolated from bone marrow aspirates and expanded ex vivo under various culture conditions. MSCs under optimal good medical practice (GMP)-conform culture conditions showed the typical morphology, immunophenotype, and plasticity. Biochemically, the activities of
beta-hexosaminidase A, total
beta-hexosaminidase,
arylsulfatase A (ASA), and
beta-galactosidase measured in MSCs were comparable to those in fibroblasts of healthy donors. These four
enzymes were interesting for their expression in MSCs, as each of them is defective, respectively, in well-known neurometabolic diseases. We found that MSCs released significant amounts of ASA into the media. In coculture experiments, fibroblasts from patients with
metachromatic leukodystrophy, who are deficient for ASA, took up a substantial amount of ASA that was released into the media from MSCs.
Mannose-6-phosphate (M6P) inhibited this uptake, which was in accordance with the M6P receptor-mediated uptake of lysosomal
enzymes. Taken together, we show that MSCs produce appreciable amounts of lysosomal
enzyme activities, making these cells first-choice candidates for providing metabolic correction when given to
enzyme-deficient patients. With the example of ASA, it was also shown that an
enzyme secreted from MSCs is taken up by
enzyme-deficient patient fibroblasts. Given the plasticity of MSCs, these cells represent an interesting add-on option for cellular
therapy in children undergoing
bone marrow transplantation for
lysosomal storage diseases and other neurometabolic diseases.