title: Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques.
abstract: Skeletal stem cells (SSC) are a sub-population of bone marrow stromal cells that reside in postnatal bone marrow with osteogenic, chondrogenic and adipogenic differentiation potential. SSCs reside only in the bone marrow and have organisational and regulatory functions in the bone marrow microenvironment and give rise to the haematopoiesis-supportive stroma. Their differentiation capacity is restricted to skeletal lineages and therefore the term SSC should be clearly distinguished from mesenchymal stem cells which are reported to exist in extra-skeletal tissues and, critically, do not contribute to skeletal development. SSCs are responsible for the unique regeneration capacity of bone and offer unlimited potential for application in bone regenerative therapies. A current unmet challenge is the isolation of homogeneous populations of SSCs, in vitro, with homogeneous regeneration and differentiation capacities. Challenges that limit SSC isolation include a) the scarcity of SSCs in bone marrow aspirates, estimated at between 1 in 10-100,000 mononuclear cells; b) the absence of specific markers and thus the phenotypic ambiguity of the SSC and c) the complexity of bone marrow tissue. Microfluidics provides innovative approaches for cell separation based on bio-physical features of single cells. Here we review the physical principles underlying label-free microfluidic sorting techniques and review their capacity for stem cell selection/sorting from complex (heterogeneous) samples.
authors.affiliation: Faculty of Physical Sciences and Engineering, Institute for Life Sciences, University of Southampton, SO17 1BJ, United Kingdom.; Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, Southampton General Hospital, Tremona Road, SO16 6YD Southampton, United Kingdom.. Electronic address: j.xavier@soton.ac.uk.
authors.forename: Miguel
authors.initials: M
authors.lastname: Xavier
authors.affiliation: Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, Southampton General Hospital, Tremona Road, SO16 6YD Southampton, United Kingdom.. Electronic address: roco@soton.ac.uk.
authors.forename: Richard O C
authors.initials: ROC
authors.lastname: Oreffo
authors.affiliation: Faculty of Physical Sciences and Engineering, Institute for Life Sciences, University of Southampton, SO17 1BJ, United Kingdom.. Electronic address: hm@esc.soton.ac.uk.
authors.forename: Hywel
authors.initials: H
authors.lastname: Morgan
mesh_terms: D000818:Animals; D002469:Cell Separation / Q000379:methods*; D006801:Humans; D059630:Mesenchymal Stem Cells; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000379:methods*
keywords: Bone regeneration; Cell separation; Cell sorting; Human bone marrow; Label-free; Microfluidics; Skeletal stem cells