The properties of human Schwann cells: Lessons from in vitro culture and transplantation studies

Abstract

Human Schwann cells (hSCs) can be isolated directly from peripheral nerve and cultured using methods similar to those used for SCs from other species. Yet, important interspecies differences are revealed when the primary or expanded hSCs are compared to their nonhuman counterparts. This review addresses the special properties of nerve-derived hSCs that have resulted to date from both in vitro studies and in vivo research on cell transplantation in animal models and human subjects. A consensus has yet to emerge about the essential attributes of cultured normal hSCs. Thus, an emphasis is placed on the importance of validating hSC cultures by means of purity, identity, and biological activity to reliably use them as in vitro models of the SC phenotype and cell therapy products for injury repair. Combining traditional immunological methods, high-resolution omics approaches, and assorted cell-based assays is so far the best approach to unequivocally identify hSC populations obtained by direct isolation or derivation from stem cells. Special considerations are required to understand and manage the variability and heterogeneity proper of donor batches, as well as to evaluate risk factors. This is particularly important if the intended use of the hSCs is implantation in the human body, diagnosis of disease, or drug testing aimed at targeting any aspect of SC function in human patients. To conclude, in view of their unique properties, new concepts and methods are needed to better understand the biology of hSCs and exploit their full potential in basic science and regenerative medicine.

Magnetic separation of peripheral nerve-resident cells underscores key molecular features of human Schwann cells and fibroblasts: an immunochemical and transcriptomics approach

“…For practical purposes, and considering the fact that normal nerve tissues were used to derive our cultures, we have regarded S100β and p75 NGFR equally suitable for human SC identification regardless of the cellular localization of the antigenic signal. However, caution should be taken in interpreting S100β immunostaining results in other types of cultures such as those suspected of CNS glia contamination because S100β positive cells that are not SCs are likely to emerge 13 , 28 .…”

“…Overall, these results indicate the need for cell type-specific immunolabeling in order to unequivocally discern SCs and non-glial cells. This is important considering the morphological variability and the antigenic heterogeneity that lies within SCs and fibroblasts of human origin 13 , 14 .…”

“…Nevertheless, it is possible that our cultures contain perineurial cells that have lost typical cell adhesion markers such as Claudin-1. Whether different nerves render cultures with different characteristics or levels of purity is unknown, as many sources of variability can affect the quality and quantity of the human SC cultures 13 . The heterogeneity of the populations may reflect the influence of extracellular factors in gene expression profiles or an unintended selection of the most aggressive phenotypes.…”

“…The heterogeneity of the populations may reflect the influence of extracellular factors in gene expression profiles or an unintended selection of the most aggressive phenotypes. Yet, we assume that basic characteristics, such as the expression of lineage-specific genes, are rather constant and not artefactual from the culture conditions 13 , 28 . To this end, more studies are needed to trace the SCs and non-glial cells from the nerve to the culture.…”

“…1 ) that was validated using > 10 different cultures. In addition, we present an in-depth analysis of purified SCs and fibroblasts of human origin, which have been understudied when compared to cells from experimental animals 13 . Our workflow can suit the needs of assorted basic and translational projects in which understanding human SC function, or using the cells themselves as a cell product, has relevance to investigations on peripheral nerve development, therapy, or neurodegenerative disease.…”