The much greater apparent cortical tension found by filtration may thus reflect the contribution of the MSC nucleus to resisting deformation upon entry into a pore, as suggested by the micropipette studies of Ribeiro and Dahl47

The much greater apparent cortical tension found by filtration may thus reflect the contribution of the MSC nucleus to resisting deformation upon entry into a pore, as suggested by the micropipette studies of Ribeiro and Dahl47. of MSCs may be mitigated. Thus it is suggested that selecting fractions of the MSC population according to cell deformability may permit optimization of entrapment at sites targeted for tissue regeneration. by a variety of techniques: micropipette aspiration41, 44, 47, Sulfaphenazole optical tweezers41, 55 and optical stretching36, 42, capillary-based microfluidic systems36, 37, analysis of diffraction patterns (ektacytometry) of suspensions under shear60, cell manipulation using atomic force microscopy12, 33, 42, imaging cell stretching in extensional flows within a microfluidic chamber9, 28, transit time through a microfluidic chamber32, mechanical manipulation through artificial microscale barriers63, and pressure driven filtration through porous filters56. It is now well accepted that SCs are viscoelastic in nature, since the more rapid the deformation the stiffer the cell appears, and similar Sulfaphenazole to leukocytes, the cell nucleus contributes overwhelmingly to its resistance to deformation during passage through capillary sized pores11, 47. It is well recognized that SC differentiation can be directed by the extracellular stiffness of its surroundings, and SC differentiation is often accompanied by alteration of structural properties of the nucleus11, 12, 42, 43 and the cell membrane55. Deformability has been identified as an early biomarker for pluripotent stem cell differentiation and is likely linked to nuclear structural changes28. Thus, it has been hypothesized that the therapeutic efficacy of mesenchymal stem cells (MSCs) in tissue engineering and regenerative medicine is determined by their unique biological, mechanical, and physicochemical characteristics, which remain to be fully elucidated55. To elucidate the potential Sulfaphenazole for cell sequestration within the microvasculature, studies of blood cell deformability have aimed to simulate the passage of blood cells through capillary sized pores in filters. The seminal studies of Gregersen et al.29 using polycarbonate sieves with uniform cylindrical pores (typically on the order of 5 m) have been followed by numerous studies using either steady state or transient filtration methods to characterize cell deformability. It is generally recognized that the initial cell deformation of a cell entering an orifice of a given size is the primary determinant of the ease with which a blood cell may enter a capillary10, 46, 52. Quantitative indices of cell deformability have been derived from measurement of the flow of a suspension of cells through a filter in terms of the resistance to flow for a specified pore density and pore diameter. Using steady-flow filtration methods, a quantitative index of cell deformability has been defined in terms of the ratio () of the resistance to flow (R = P/Q) through a filter pore Sulfaphenazole in the presence and absence of cells ( = RCELLS/RBUFFER)52. In contrast, transient filtration techniques7, 16, 17 have demonstrated the ability to elucidate the heterogeneity of cell properties within a given sample. To explicitly describe the heterogeneous properties F2R of a population of cells, prior studies have extended the bolus filtration technique described by Downey and Worthen17, to assess the average deformability of the circulating population of WBCs in terms of the yield pressure (within a WBC suspension21. These studies also suggested that the cortical shell model22 of a WBC may provide a single parameter, the cortical tension (0), that is representative of cell deformability. As shown therein, this analysis was extended to describe the filterability of a population Sulfaphenazole of WBCs of heterogeneous diameter through the capillary network of the cremaster muscle (hamster) with a known heterogeneous distribution of capillary diameters to determine a comparable measure of (cannot pass through a filter pore of diameter DPORE unless a.

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