65complications such as interstitial lung disease and renal failure can complicate the
disease in the long term. Abnormal T cell activation, autoantibody production (anti
SCL-70) and cytokine production have been incriminated in the pathogenesis of the
disease. Extensive studies using hematopoietic stem cells have been studied in the
management of systemic sclerosis and include the ASSIST, ASTIS and SCOT trials
[ 50 ]. While newer small group studies have reported improvement in digital ulcers
and improved blood supply to the digits following intravenous mesenchymal stem
cell infusion, with no significant adverse side effects; larger trials to validate such
findings are pending [ 51 , 52 ].
4.8.3 Inflammatory Myopathies
Dermatomyositis and polymyositis are inflammatory myopathies which are charac-
terized by proximal muscle weakness and elevated muscle enzymes such as creatine
kinase. These are thought to be mediated by complement activation system and
cytotoxic CD8+ T cells respectively, which induce myonecrosis [ 50 ].
Small studies using mesenchymal stem cells in patients refractory to therapy for
these conditions have reported improvement in muscle strength, reduction in cre-
atine kinase levels as well as improvement in interstitial lung disease associated
with these inflammatory myopathies [ 53 ].
4.9 Inborn Errors of Metabolism
4.9.1 Metachromatic Leukodystrophy and Hurler Syndrome:
(MLD)
MLD is an inherited disorder characterized by lack of enzyme arylsulfatase-A that
affects the white matter, resulting in progressive demyelination of both central and
peripheral nervous systems. No definitive cure exists for this disorder that results in
progressive loss of cognitive and motor function.
Several studies have reported the efficacy of hematopoietic stem cell transplanta-
tion in stabilizing the course of the disease with some case reports showing long- term
improvement in MRI appearance of white matter lesions as well as spectroscopy
findings in patients followed for over 2 years after transplantation. However due to
limited availability of matched donors, limited entry of hematopoietic stem into the
brain and greater side effects, alternate cell based therapies such as use of mesenchy-
mal cells have been studied [ 54 ]. Due to their ability to differentiate into neuronal
cells, ability to migrate in the brain, including the “homing” phenomenon where they
selectively accumulate in damaged/inflamed areas of the brain, mesenchymal cells
have been studied in treating MLD. In a small study of patients concomitantly treated
4 Clinical Applications of Stem Cell Transplant in Treating Non-Hematologic...