Improving Schwann Cell Differentiation from Human Adipose Stem Cells with Metabolic Glycoengineering

Abstract

Schwann cells (SCs) are myelinating cells that promote peripheral nerve regeneration. When nerve lesions form, SCs are destroyed, ultimately hindering nerve repair. The difficulty in treating nerve repair is exacerbated due to SC’s limited and slow expansion capacity. Therapeutic use of adipose-derived stem cells (ASCs) is emerging in combating peripheral nerve injury due to these cells’ SC differentiation capability and can be harvested easily in large numbers. Despite ASC’s therapeutic potential, their transdifferentiation period typically takes more than two weeks. In this study, we demonstrate that metabolic glycoengineering (MGE) technology enhances ASC differentiation into SCs. Specifically, the sugar analog Ac5ManNTProp (TProp), which modulates cell surface sialylation, significantly improved ASC differentiation with upregulated SC protein S100β and p75NGFR expression and elevated the neurotrophic factors nerve growth factor beta (NGFβ) and glial cell-line-derived neurotrophic factor (GDNF). TProp treatment remarkably reduced the SC transdifferentiation period from about two weeks to two days in vitro, which has the potential to improve neuronal regeneration and facilitate future use of ASCs in regenerative medicine.

Tight Regulation of Mechanotransducer Proteins Distinguishes the Response of Adult Multipotent Mesenchymal Cells on PBCE-Derivative Polymer Films with Different Hydrophilicity and Stiffness

“…The different responses of hBM-MSCs and hASCs might be dependent on the ontogenetic origin of both multipotent cell types, since hBM-MSCs reside in the bone marrow whereas hASCs reside in soft tissue; therefore, the former are more sensitive to the stiffness variations in both films compared to the latter [ 34 , 35 , 36 , 37 , 38 , 40 , 84 ].…”

Glycan Modifications as Regulators of Stem Cell Fate

“…Specifically, the sugar analog tProp significantly enhanced ASC differentiation, leading to elevated expression of SC proteins S100β and p75NGFR, along with heightened levels of neurotrophic factors such as nerve growth factor beta (NGFβ) and glial cell-line-derived neurotrophic factor (GDNF). Remarkably, tProp treatment reduced the SC transdifferentiation period from approximately two weeks to just two days in vitro [125]. This breakthrough holds the potential to significantly improve neuronal regeneration.…”

“…Thereby, advancing the in vivo applications and potentially paving the way for clinical translation of these MGE analogs. Building on the previous studies, the group further expanded the applications of thiol-modified MGE analogs by demonstrating the ability of Ac5ManNTProp (tProp) to facilitate Schwann cells (SCs) differentiation from Adipose-derived stem cells (ASCs) [125]. SCs are myelinating cells essential for peripheral nerve regeneration [126].…”