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  • Article
    Citation - WoS: 16
    Citation - Scopus: 19
    A Pumpless Monolayer Microfluidic Device Based on Mesenchymal Stem Cell-Conditioned Medium Promotes Neonatal Mouse in Vitro Spermatogenesis
    (Bmc, 2023) Onen, Selin; Atik, Ali Can; Gizer, Merve; Kose, Sevil; Yaman, Onder; Kulah, Haluk; Korkusuz, Petek
    BackgroundChildhood cancer treatment-induced gonadotoxicity causes permanent infertility/sub-infertility in nearly half of males. The current clinical and experimental approaches are limited to cryopreservation of prepubertal testicular strips and in vitro spermatogenesis which are inadequate to achieve the expanded spermatogonial stem/progenitor cells and spermatogenesis in vitro. Recently, we reported the supportive effect of bone marrow-derived mesenchymal cell co-culture which is inadequate after 14 days of culture in static conditions in prepubertal mouse testis due to lack of microvascular flow and diffusion. Therefore, we generated a novel, pumpless, single polydimethylsiloxane-layered testis-on-chip platform providing a continuous and stabilized microfluidic flow and real-time cellular paracrine contribution of allogeneic bone marrow-derived mesenchymal stem cells.MethodsWe aimed to evaluate the efficacy of this new setup in terms of self-renewal of stem/progenitor cells, spermatogenesis and structural and functional maturation of seminiferous tubules in vitro by measuring the number of undifferentiated and differentiating spermatogonia, spermatocytes, spermatids and tubular growth by histochemical, immunohistochemical, flow cytometric and chromatographic techniques.ResultsBone marrow-derived mesenchymal stem cell-based testis-on-chip platform supported the maintenance of SALL4(+) and PLZF(+) spermatogonial stem/progenitor cells, for 42 days. The new setup improved in vitro spermatogenesis in terms of c-Kit(+) differentiating spermatogonia, VASA(+) total germ cells, the meiotic cells including spermatocytes and spermatids and testicular maturation by increasing testosterone concentration and improved tubular growth for 42 days in comparison with hanging drop and non-mesenchymal stem cell control.ConclusionsFuture fertility preservation for male pediatric cancer survivors depends on the protection/expansion of spermatogonial stem/progenitor cell pool and induction of in vitro spermatogenesis. Our findings demonstrate that a novel bone marrow-derived mesenchymal stem cell-based microfluidic testis-on-chip device supporting the maintenance of stem cells and spermatogenesis in prepubertal mice in vitro. This new, cell therapy-based microfluidic platform may contribute to a safe, precision-based cell and tissue banking protocols for prepubertal fertility restoration in future.
  • Book Part
    Citation - Scopus: 1
    Boundary-Element Method in Microfluidics
    (Springer Science+Business Media, 2015) Çetin, Barbaros; Baranoğlu, Besim
  • Article
    Citation - WoS: 22
    Citation - Scopus: 28
    Modeling of Dielectrophoretic Particle Motion: Point Particle Versus Finite-Sized Particle
    (Wiley, 2017) Cetin, Barbaros; Oner, S. Dogan; Baranoglu, Besim
    Dielectrophoresis (DEP) is a very popular technique for microfluidic bio-particle manipulation. For the design of a DEP-based microfluidic device, simulation of the particle trajectory within the microchannel network is crucial. There are basically two approaches: (i) point-particle approach and (ii) finite-sized particle approach. In this study, many aspects of both approaches are discussed for the simulation of direct current DEP, alternating current DEP, and traveling-wave DEP applications. Point-particle approach is implemented using Lagrangian tracking method, and finite-sized particle is implemented using boundary element method. The comparison of the point-particle approach and finite-sized particle approach is presented for different DEP applications. Moreover, the effect of particle-particle interaction is explored by simulating the motion of closely packed multiple particles for the same applications, and anomalous-DEP, which is a result of particle-wall interaction at the close vicinity of electrode surface, is illustrated.
  • Conference Object
    Citation - WoS: 1
    Citation - Scopus: 3
    Boundary Element Method for Optical Force Calibration in Microfluidic Dual-Beam Optical Trap
    (Spie-int Soc Optical Engineering, 2015) Solmaz, Mehmet E.; Cetin, Barbaros; Baranoglu, Besim; Serhathoglu, Murat; Biyikh, Neemi
    The potential use of optical forces in microfluidic environment enables highly selective bio-particle manipulation. Manipulation could be accomplished via trapping or pushing a particle due to optical field. Empirical determination of optical force is often needed to ensure efficient operation of manipulation. The external force applied to a trapped particle in a microfluidic channel is a combination of optical and drag forces. The optical force can be found by measuring the particle velocity for a certain laser power level and a multiplicative correction factor is applied for the proximity of the particle to the channel surface. This method is not accurate especially for small microfluidic geometries where the particle size is in Mie regime and is comparable to channel cross section. In this work, we propose to use Boundary Element Method (BEM) to simulate fluid flow within the micro-channel with the presence of the particle to predict drag force. Pushing experiments were performed in a dual-beam optical trap and particle's position information was extracted. The drag force acting on the particle was then obtained using BEM and other analytical expressions, and was compared to the calculated optical force. BEM was able to predict the behavior of the optical force due to the inclusion of all the channel walls.