1.Transplantation of Differentiated Tonsil-Derived Mesenchymal Stem Cells Ameliorates Murine Duchenne Muscular Dystrophy via Autophagy Activation
Saeyoung PARK ; Soyeon JEONG ; Yu Hwa NAM ; Yoonji YUM ; Sung-Chul JUNG
Tissue Engineering and Regenerative Medicine 2022;19(6):1283-1294
BACKGROUND:
Skeletal muscles play many important roles in the human body and any malfunction or disorder of the skeletal muscles can lead to a reduced quality of life. Some skeletal dysfunctions are acquired, such as sarcopenia but others are congenital. Duchenne muscular dystrophy (DMD) is one of the most common forms of hereditary muscular dystrophy and is caused by a deficiency of the protein, Dystrophin. Currently, there is no clear treatment for DMD, there are only methods that can alleviate the symptoms of the disease. Mesenchymal stem cells, including tonsil-derived mesenchymal stem cells (TMSCs) have been shown to differentiate into skeletal muscle cells (TMSC-myocyte) and can be one of the resources for the treatment of DMD. Skeletal muscle cell characteristics of TMSC-myocytes have been confirmed through changes in morphology and expression of skeletal muscle markers such as Myogenin, Myf6, and MYH families after differentiation.MEOTHDS: Based on these characteristics, TMSC-myocytes have been transplanted into mdx mice, a mouse model of DMD, to investigate whether they can help improve the symptoms of DMD. The red fluorescent protein gene was transduced into TMSC (TMSC-R) for tracking transplanted cells.
RESULTS:
Prior to transplantation (TP), it was confirmed whether TMSC-R-myocytes had the same differentiation potential as TMSC-myocytes. Increased expression of dystrophin and autophagy markers in the TP group compared with the sham group was confirmed in the gastrocnemius muscle 12 weeks after TP.
CONCLUSION
These results demonstrate muscle regeneration and functional recovery of mdx via autophagy activation following TMSC-myocyte TP.
2.Therapeutic Effect of Schwann Cell-Like Cells Differentiated from Human Tonsil-Derived Mesenchymal Stem Cells on Diabetic Neuropathy in db/db Mice
Yoonji YUM ; Saeyoung PARK ; Yu Hwa NAM ; Juhee YOON ; Hyeryung SONG ; Ho Jin KIM ; Jaeseung LIM ; Sung-Chul JUNG
Tissue Engineering and Regenerative Medicine 2024;21(5):761-776
BACKGROUND:
Diabetic neuropathy (DN) is the most common complication of diabetes, and approximately 50% of patients with this disease suffer from peripheral neuropathy. Nerve fiber loss in DN occurs due to myelin defects and is characterized by symptoms of impaired nerve function. Schwann cells (SCs) are the main support cells of the peripheral nervous system and play important roles in several pathways contributing to the pathogenesis and development of DN. We previously reported that human tonsil-derived mesenchymal stem cells differentiated into SCs (TMSC-SCs), named neuronal regeneration-promoting cells (NRPCs), which cells promoted nerve regeneration in animal models with peripheral nerve injury or hereditary peripheral neuropathy.
METHODS:
In this study, NRPCs were injected into the thigh muscles of BKS-db/db mice, a commonly used type 2 diabetes model, and monitored for 26 weeks. Von Frey test, sensory nerve conduction study, and staining of sural nerve, hind foot pad, dorsal root ganglia (DRG) were performed after NRPCs treatment.
RESULTS:
Von Frey test results showed that the NRPC treatment group (NRPC group) showed faster responses to less force than the vehicle group. Additionally, remyelination of sural nerve fibers also increased in the NRPC group. After NRPCs treatment, an improvement in response to external stimuli and pain sensation was expected through increased expression of PGP9.5 in the sole and TRPV1 in the DRG.
CONCLUSION
The NRPCs treatment may alleviate DN through the remyelination and the recovery of sensory neurons, could provide a better life for patients suffering from complications of this disease.