Label-free enrichment of primary human skeletal progenitor cells using deterministic lateral displacement

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Label-free enrichment of primary human skeletal progenitor cells using deterministic lateral displacement. / Xavier, Miguel; Holm, Stefan H.; Beech, Jason P.; Spencer, Daniel; Tegenfeldt, Jonas O.; Oreffo, Richard O.C.; Morgan, Hywel.

I: Lab on a Chip, Vol. 19, Nr. 3, 2019, s. 513-523.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Xavier, Miguel ; Holm, Stefan H. ; Beech, Jason P. ; Spencer, Daniel ; Tegenfeldt, Jonas O. ; Oreffo, Richard O.C. ; Morgan, Hywel. / Label-free enrichment of primary human skeletal progenitor cells using deterministic lateral displacement. I: Lab on a Chip. 2019 ; Vol. 19, Nr. 3. s. 513-523.

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TY - JOUR

T1 - Label-free enrichment of primary human skeletal progenitor cells using deterministic lateral displacement

AU - Xavier, Miguel

AU - Holm, Stefan H.

AU - Beech, Jason P.

AU - Spencer, Daniel

AU - Tegenfeldt, Jonas O.

AU - Oreffo, Richard O.C.

AU - Morgan, Hywel

PY - 2019

Y1 - 2019

N2 - Skeletal stem cells (SSCs) are present in bone marrow (BM) and offer great potential for bone regenerative therapies. However, in the absence of a unique marker, current sorting approaches remain challenging in the quest for simple strategies to deliver SSCs with consistent regeneration and differentiation capacities. Microfluidics offers the possibility to sort cells marker-free, based on intrinsic biophysical properties. Recent studies indicate that SSCs are stiffer than leukocytes and are contained within the larger cell fraction in BM. This paper describes the use of deterministic lateral displacement (DLD) to sort SSCs based on cell size and stiffness. DLD is a technology that uses arrays of micropillars to sort cells based on their diameter. Cell deformation within the device can change the cell size and affect sorting - here evidenced using human cell lines and by fractionation of expanded SSCs. Following sorting, SSCs remained viable and retained their capacity to form clonogenic cultures (CFU-F), indicative of stem cell potential. Additionally, larger BM cells showed enhanced capacity to form CFU-F. These findings support the theory that SSCs are more abundant within the larger BM cell fraction and that DLD, or other size-based approaches, could be used to provide enriched SSC populations with significant implications for stem cell research and translation to the clinic.

AB - Skeletal stem cells (SSCs) are present in bone marrow (BM) and offer great potential for bone regenerative therapies. However, in the absence of a unique marker, current sorting approaches remain challenging in the quest for simple strategies to deliver SSCs with consistent regeneration and differentiation capacities. Microfluidics offers the possibility to sort cells marker-free, based on intrinsic biophysical properties. Recent studies indicate that SSCs are stiffer than leukocytes and are contained within the larger cell fraction in BM. This paper describes the use of deterministic lateral displacement (DLD) to sort SSCs based on cell size and stiffness. DLD is a technology that uses arrays of micropillars to sort cells based on their diameter. Cell deformation within the device can change the cell size and affect sorting - here evidenced using human cell lines and by fractionation of expanded SSCs. Following sorting, SSCs remained viable and retained their capacity to form clonogenic cultures (CFU-F), indicative of stem cell potential. Additionally, larger BM cells showed enhanced capacity to form CFU-F. These findings support the theory that SSCs are more abundant within the larger BM cell fraction and that DLD, or other size-based approaches, could be used to provide enriched SSC populations with significant implications for stem cell research and translation to the clinic.

U2 - 10.1039/c8lc01154k

DO - 10.1039/c8lc01154k

M3 - Article

VL - 19

SP - 513

EP - 523

JO - Lab on a Chip - Miniaturisation for Chemistry and Biology

T2 - Lab on a Chip - Miniaturisation for Chemistry and Biology

JF - Lab on a Chip - Miniaturisation for Chemistry and Biology

SN - 1473-0189

IS - 3

ER -