Differentiation of Human Tonsil-Derived Mesenchymal Stem Cells into Schwann-Like Cells Improves Neuromuscular Function in a Mouse Model of Charcot-Marie-Tooth Disease Type 1A

• Published in: International journal of molecular sciences Vol. 19; no. 8; p. 2393
• Main Authors: Park, Saeyoung, Jung, Namhee, Myung, Seoha, Choi, Yoonyoung, Chung, Ki Wha, Choi, Byung-Ok, Jung, Sung-Chul
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.08.2018; MDPI
• Subjects: Animals; Atrophy; Brain-derived neurotrophic factor; Calcium-binding protein; Cell Differentiation; Charcot-Marie-Tooth disease; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - metabolism; Charcot-Marie-Tooth Disease - pathology; Charcot-Marie-Tooth Disease - therapy; Charcot-Marie-Tooth disease type 1A; Demyelination; Differentiation; Disease Models, Animal; Glial cell line-derived neurotrophic factor; Glial fibrillary acidic protein; Growth factors; Heterografts; Humans; Lymphocytes B; Male; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Mesenchyme; Mice; Mice, Mutant Strains; Muscles; Myelination; Nerve growth factor receptors; neuromuscular regeneration; Neuronal-glial interactions; Palatine Tonsil - metabolism; Palatine Tonsil - pathology; Patients; Peripheral myelin protein 22; Phenotypes; Protein B; Proteins; Recovery of Function; Regeneration; remyelination; S100b protein; Schwann cells; Schwann Cells - metabolism; Schwann Cells - pathology; Schwann Cells - transplantation; Stem cell transplantation; Stem cells; Thigh; Tonsil; tonsil-derived mesenchymal stem cells; Transplantation; tonsil-derived mesenchymal stem cells; Charcot-Marie-Tooth disease type 1A; Schwann cells; neuromuscular regeneration; remyelination
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19082393

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited motor and sensory neuropathy, and is caused by duplication of , alterations of which are a characteristic feature of demyelination. The clinical phenotype of CMT1A is determined by the degree of axonal loss, and patients suffer from progressive muscle weakness and impaired sensation. Therefore, we investigated the potential of Schwann-like cells differentiated from human tonsil-derived stem cells (T-MSCs) for use in neuromuscular regeneration in trembler-J (Tr-J) mice, a model of CMT1A. After differentiation, we confirmed the increased expression of Schwann cell (SC) markers, including glial fibrillary acidic protein (GFAP), nerve growth factor receptor (NGFR), S100 calcium-binding protein B (S100B), glial cell-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), which suggests the differentiation of T-MSCs into SCs (T-MSC-SCs). To test their functional efficiency, the T-MSC-SCs were transplanted into the caudal thigh muscle of Tr-J mice. Recipients' improved locomotive activity on a rotarod test, and their sciatic function index, which suggests that transplanted T-MSC-SCs ameliorated demyelination and atrophy of nerve and muscle in Tr-J mice. Histological and molecular analyses showed the possibility of in situ remyelination by T-MSC-SCs transplantation. These findings demonstrate that the transplantation of heterologous T-MSC-SCs induced neuromuscular regeneration in mice and suggest they could be useful for the therapeutic treatment of patients with CMT1A disease.