The Clinical Outcome of Hurler Syndrome after Stem Cell Transplantation

Enzyme delivery to the peripheral tissues and the central nervous system after stem cell transplantation.

In the peripheral tissues, the donor monocytes are able to cross the capillary wall, after which they differentiate into tissue-macrophages and secrete the deficient enzyme for delivery to the various cells. In addition, these peripheral tissues will presumably also benefit from the freely circulating enzymes, secreted by the donor leucocytes, because these enzymes are able to cross these capillary walls as well. Likewise, in enzyme replacement therapy, the intravenously administered enzymes are able to cross the capillary wall of these peripheral tissues.

In the central nervous system (CNS), the donor monocytes cross the blood-brain barrier and differentiate into microglia. These ‘CNS macrophages’ deliver the deficient enzyme to the neurons and other cells in the CNS. As freely circulating enzymes in the bloodstream are not able to cross the blood-brain barrier, the brains depend on these donor monocytes alone. This explains why enzyme replacement therapy is not beneficial for the disease manifestations involving the CNS in contrast to a successful stem cell transplantation.