The quest of cell surface markers for stem cell therapy

Stem cells and their derivatives are novel pharmaceutics that have the potential for use as tissue replacement therapies. However, the heterogeneous characteristics of stem cell cultures have hindered their biomedical applications. In theory and practice, when cell type-specific or stage-specific cell surface proteins are targeted by unique antibodies, they become highly efficient in detecting and isolating specific cell populations. There is a growing demand to identify reliable and actionable cell surface markers that facilitate purification of particular cell types at specific developmental stages for use in research and clinical applications. The identification of these markers as very important members of plasma membrane proteins, ion channels, transporters, and signaling molecules has directly benefited from proteomics and tools for proteomics-derived data analyses. Here, we review the methodologies that have played a role in the discovery of cell surface markers and introduce cutting edge single cell proteomics as an advanced tool. We also discuss currently available specific cell surface markers for stem cells and their lineages, with emphasis on the nervous system, heart, pancreas, and liver. The remaining gaps that pertain to the discovery of these markers and how single cell proteomics and identification of surface markers associated with the progenitor stages of certain terminally differentiated cells may pave the way for their use in regenerative medicine are also discussed.