Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration

Abstract

Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.

Application of differentiated human tonsil–derived stem cells to trembler‐J mice

“…Furthermore, MSCs show immunomodulatory ability both in vitro and in vivo . Tonsil‐derived MSCs (T‐MSCs) show typical features of MSCs, including the ability to differentiate into tissues of the 3 primary germ layers . They also exhibit similar characteristics to bone marrow–derived MSCs (BM‐MSCs) and adipose tissue–derived MSCs (ASCs) .…”

“…[18][19][20]22 Tonsilderived MSCs (T-MSCs) show typical features of MSCs, including the ability to differentiate into tissues of the 3 primary germ layers. 17,[24][25][26][27] They also exhibit similar characteristics to bone marrowderived MSCs (BM-MSCs) and adipose tissuederived MSCs (ASCs). 28 Nevertheless, the effects of donor age, long-term culture (15 passages), and cryopreservation on T-MSCs showed that they were maintained in terms of morphology, cell surface markers, and differentiation potential.…”

Application of Tonsil-Derived Mesenchymal Stem Cells in Tissue Regeneration: Concise Review

“…In addition to their mesodermal differentiation potential (bone, cartilage, and fat), it was verified that TMSCs have the capacity to differentiate into endodermal lineage, expressing markers of parathyroid cells . Subsequently, other studies also identified differentiation capacities of TMSCs into various cell types, including myocytes , insulin‐releasing cells , neuron‐like or glial cells , tenocytes , and hepatocytes (Fig. ).…”

“…Among various mesodermal differentiation capacities, osteogenesis is by far the most thoroughly studied functional phenotype of TMSCs . TMSCs cultured under osteogenic differentiation factors for 21 days increased the gene and protein expression levels of osteocalcin (OC) and alkaline phosphatase (ALP) as well as matrix mineralization as visualized by Alizarin red S staining . However, the expression of both OC and ALP was lower in osteogenically differentiated TMSCs compared with those of osteogenically differentiated BM‐MSCs .…”

“…Similar to BM‐MSCs, TMSCs have a potential to differentiate into either neuron‐like or glial cells . In a 3D hybrid thermogel that fabricates growth factor‐releasing microspheres, TMSCs expressed phenotypes similar to immature neurons, exhibiting multipolar elongation with weak expression of neuronal markers such as neuronal growth factor, nuclear receptor‐related protein, and neuron‐specific enolase .…”