Recent Patents and Advances on Tag-Less Microfluidic Stem Cell Sorting Methods: Applications for Perinatal Stem Cell Isolation

Interest in stem cell separation and purification from easily accessible clinical specimens is booming due to the increase of cell therapy applications. The recovery of pluripotent or multipotent stem cells in human sources different from the embryo requires the use of effective methods of cell sorting/enrichment. Among these sources, perinatal tissues retain cells with pivotal stem cell features such as high self-renewal ability, wide differentiation potential and immunomodulatory properties. In this perspective, methods exploiting cell biophysical differences in a less dependent process of identification based on specific markers are therefore promising. These methods allow cell isolation irrespective of the broad and diversified surface antigenic panel that usually limits the ability to easily distinguish cells as in the case of mesenchymal stromal/stem cell separation. In addition, the use of non- or minimally invasive tag-less techniques might be a way to preserve stem cell features of the selected product and reduce regulatory issues related to their use in regenerative applications. In this review, non-invasive cell sorting techniques based on microfluidic systems and relevant patents are described. In particular applications of emerging separation approach, Field-Flow Fractionation (FFF), for perinatal stem cell sorting are cited. Protocols and applications based on FFF-derived techniques are detailed.