Reprogramming the Stem Cell Behavior by Shear Stress and Electric Field Stimulation: Lab-on-a-Chip Based Biomicrofluidics in Regenerative Medicine

AbstractThe biophysical cues of endogenous origin, i.e., shear stress and electric field, are known to significantly modulate cell functionality, in vitro. While this has been relatively well investigated in conventional petri dish culture, it is important to validate such important phenomenon in physiologically simulated cellular microenvironment. In this perspective, this review critically discusses the importance of lab-on-a-chip (LOC)-based microfluidic devices to probe into this aspect to develop an insight towards the application in regenerative medicine. While reviewing several literature reports, an emphasis has been placed to unravel the intriguing aspects of shear and electric field modulated differentiation of stem cells in the biomicrofluidics devices. The potential application focusing the stem cell culture was emphasized in this article as the stem cells are the foundation of tissue regeneration. Several challenges in tissue regeneration and introduction of personalized medicine could be addressed through microfluidic technology. Culturing of organ-specific multiple cell types within lab-on-a-chip and biophysical stimulation mediated activations of intracellular signal transduction under gradient shear/electric field are highlighted in this review.Lay SummaryConceptually, regenerative medicine is considered as an emerging approach for treating traumatized, malfunctional anatomical parts of the patients with stem cells to establish normal functionality of the tissue. The regenerated tissue should preferably be the patients’ autologous tissue, grown under artificially created in vivo physiological environment. Biomicrofluidic-based lab-on-a-chip technology enables to perform in vitro cell/tissue engineering under endogenous cues, like shear and electric field.Therefore, this review discusses two aspects of regenerative medicine in terms of autologous transplantation of cells/tissues to improvise personalized regenerative medicine and to recreate an organ-specific tissue under the influence of biophysical stimulation in an attempt to improve the physiological functionality. Graphical abstractBiomicrofluidics based Lab-on-a-Chip devices have improvised the tissue regenerative approaches towards into the direction of personalised medicine.

[1]  Marco Rasponi,et al.  Controlled electromechanical cell stimulation on-a-chip , 2015, Scientific Reports.

[2]  Ivar Giaever,et al.  Use of Electric Fields to Monitor the Dynamical Aspect of Cell Behavior in Tissue Culture , 1986, IEEE Transactions on Biomedical Engineering.

[3]  T. Krieg,et al.  Inflammation in wound repair: molecular and cellular mechanisms. , 2007, The Journal of investigative dermatology.

[4]  H. Sorg,et al.  Wound Repair and Regeneration , 2012, European Surgical Research.

[5]  Gang Li,et al.  Highly sensitive enumeration of circulating tumor cells in lung cancer patients using a size-based filtration microfluidic chip. , 2014, Biosensors & bioelectronics.

[6]  A. Redaelli,et al.  Electrical conditioning of adipose‐derived stem cells in a multi‐chamber culture platform , 2014, Biotechnology and bioengineering.

[7]  M Kokoris,et al.  Rare cancer cell analyzer for whole blood applications: automated nucleic acid purification in a microfluidic disposable card. , 2005, Methods.

[8]  M. W. Vaughn,et al.  Microfluidic-based diagnostics for cervical cancer cells. , 2006, Biosensors & bioelectronics.

[9]  A. Franco-Obregón,et al.  Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields , 2017, Scientific Reports.

[10]  Bikramjit Basu,et al.  Electrically driven intracellular and extracellular nanomanipulators evoke neurogenic/cardiomyogenic differentiation in human mesenchymal stem cells. , 2016, Biomaterials.

[11]  Aaron R Wheeler,et al.  A microfluidic membrane device to mimic critical components of the vascular microenvironment. , 2011, Biomicrofluidics.

[12]  Nitish Thakor,et al.  Investigation of nerve injury through microfluidic devices , 2014, Journal of The Royal Society Interface.

[13]  Xuena Zhu,et al.  Lab-on-chip device for single cell trapping and analysis , 2014, Biomedical microdevices.

[14]  Roland Zengerle,et al.  Microfluidic platforms for lab-on-a-chip applications. , 2007, Lab on a chip.

[15]  M. Brueckner,et al.  Cilia are at the heart of vertebrate left-right asymmetry. , 2003, Current opinion in genetics & development.

[16]  Jun-Ha Hwang,et al.  Shear Stress Induced by an Interstitial Level of Slow Flow Increases the Osteogenic Differentiation of Mesenchymal Stem Cells through TAZ Activation , 2014, PloS one.

[17]  Falk Wottawah,et al.  Oral cancer diagnosis by mechanical phenotyping. , 2009, Cancer research.

[18]  N. Yuldasheva,et al.  Piezo1 integration of vascular architecture with physiological force , 2014, Nature.

[19]  L K Chin,et al.  Production of reactive oxygen species in endothelial cells under different pulsatile shear stresses and glucose concentrations. , 2011, Lab on a chip.

[20]  Michael R Hamblin,et al.  Microfluidic systems for stem cell-based neural tissue engineering. , 2016, Lab on a chip.

[21]  Stephen R Quake,et al.  Microfluidic single-cell mRNA isolation and analysis. , 2006, Analytical chemistry.

[22]  Richard Nuccitelli,et al.  A role for endogenous electric fields in wound healing. , 2003, Current topics in developmental biology.

[23]  F. Fregni,et al.  Noninvasive Brain Stimulation with Low-Intensity Electrical Currents: Putative Mechanisms of Action for Direct and Alternating Current Stimulation , 2010, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[24]  Wenming Liu,et al.  Construction of single-cell arrays and assay of cell drug resistance in an integrated microfluidic platform. , 2016, Lab on a chip.

[25]  A. Kouzani,et al.  Microfluidic devices for cell cultivation and proliferation. , 2013, Biomicrofluidics.

[26]  Rajeev J Ram,et al.  Microfluidic chemostat and turbidostat with flow rate, oxygen, and temperature control for dynamic continuous culture. , 2011, Lab on a chip.

[27]  G. Whitesides,et al.  Fabrication of microfluidic systems in poly(dimethylsiloxane) , 2000, Electrophoresis.

[28]  Gwo-Bin Lee,et al.  A microfluidic cell culture platform for real-time cellular imaging , 2009, Biomedical microdevices.

[29]  Pamela Habibovic,et al.  Regeneration-on-a-chip? The perspectives on use of microfluidics in regenerative medicine. , 2013, Lab on a chip.

[30]  H. Abrahamse,et al.  Influence of Low Intensity Laser Irradiation on Isolated Human Adipose Derived Stem Cells Over 72 Hours and Their Differentiation Potential into Smooth Muscle Cells Using Retinoic Acid , 2011, Stem Cell Reviews and Reports.

[31]  T. Park,et al.  Integration of Cell Culture and Microfabrication Technology , 2003, Biotechnology progress.

[32]  Yi-Shiuan Liu,et al.  Mechanosensitive TRPM7 mediates shear stress and modulates osteogenic differentiation of mesenchymal stromal cells through Osterix pathway , 2015, Scientific Reports.

[33]  Roger D Kamm,et al.  Microfluidic devices for studying heterotypic cell-cell interactions and tissue specimen cultures under controlled microenvironments. , 2011, Biomicrofluidics.

[34]  J. Freund,et al.  Anisotropic shear stress patterns predict the orientation of convergent tissue movements in the embryonic heart , 2017, Development.

[35]  Beerend P. Hierck,et al.  The development of the heart and microcirculation: role of shear stress , 2008, Medical & Biological Engineering & Computing.

[36]  D. Beebe,et al.  Biological implications of polydimethylsiloxane-based microfluidic cell culture. , 2009, Lab on a chip.

[37]  Joel Voldman,et al.  nDEP microwells for single-cell patterning in physiological media. , 2007, Lab on a chip.

[38]  S. Chien,et al.  Interplay between integrins and FLK-1 in shear stress-induced signaling. , 2002, American journal of physiology. Cell physiology.

[39]  Erin M. Schuman,et al.  Microfluidic Local Perfusion Chambers for the Visualization and Manipulation of Synapses , 2010, Neuron.

[40]  David J. Anderson,et al.  Molecular Distinction and Angiogenic Interaction between Embryonic Arteries and Veins Revealed by ephrin-B2 and Its Receptor Eph-B4 , 1998, Cell.

[41]  Douglas A Lauffenburger,et al.  Microfluidic shear devices for quantitative analysis of cell adhesion. , 2004, Analytical chemistry.

[42]  J. Tarbell,et al.  Shear stress-induced release of PGE2 and PGI2 by vascular smooth muscle cells. , 1996, Biochemical and biophysical research communications.

[43]  Guanbin Song,et al.  High-level Shear Stress Stimulates Endothelial Differentiation and VEGF Secretion by Human Mesenchymal Stem Cells , 2013 .

[44]  F. Kudo,et al.  Differential effects of orbital and laminar shear stress on endothelial cells. , 2005, Journal of vascular surgery.

[45]  C. Holding.  Lab on a chip , 2004, Genome Biology.

[46]  Jiang Li,et al.  Application of microfluidic gradient chip in the analysis of lung cancer chemotherapy resistance. , 2009, Journal of pharmaceutical and biomedical analysis.

[47]  Shinji Sugiura,et al.  Pressure‐driven perfusion culture microchamber array for a parallel drug cytotoxicity assay , 2008, Biotechnology and bioengineering.

[48]  M. Poo,et al.  Orientation of neurite growth by extracellular electric fields , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  R. Nuccitelli,et al.  Endogenous electric fields in embryos during development, regeneration and wound healing. , 2003, Radiation protection dosimetry.

[50]  Yongquan Gu,et al.  Response of mesenchymal stem cells to shear stress in tissue-engineered vascular grafts , 2009, Acta Pharmacologica Sinica.

[51]  G. Madras,et al.  Intermittent electrical stimuli for guidance of human mesenchymal stem cell lineage commitment towards neural-like cells on electroconductive substrates. , 2014, Biomaterials.

[52]  Andreas Manz,et al.  Micromachining of monocrystalline silicon and glass for chemical analysis systems A look into next century's technology or just a fashionable craze? , 1991 .

[53]  Teodor Veres,et al.  Cell culture chips for simultaneous application of topographical and electrical cues enhance phenotype of cardiomyocytes. , 2009, Lab on a chip.

[54]  B. Chung,et al.  Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. , 2005, Lab on a chip.

[55]  F. Han,et al.  Cellular modulation by the elasticity of biomaterials. , 2016, Journal of materials chemistry. B.

[56]  Francis E H Tay,et al.  A quantitative observation and imaging of single tumor cell migration and deformation using a multi-gap microfluidic device representing the blood vessel. , 2006, Microvascular research.

[57]  K. Neoh,et al.  Electrical stimulation of adipose-derived mesenchymal stem cells in conductive scaffolds and the roles of voltage-gated ion channels. , 2016, Acta biomaterialia.

[58]  Numrin Thaitrong,et al.  Integrated microfluidic bioprocessor for single-cell gene expression analysis , 2008, Proceedings of the National Academy of Sciences.

[59]  Ashutosh Sharma,et al.  Vertical electric field stimulated neural cell functionality on porous amorphous carbon electrodes. , 2013, Biomaterials.

[60]  Qin Tu,et al.  An integrated microfluidic system for studying cell-microenvironmental interactions versatilely and dynamically. , 2010, Lab on a chip.

[61]  Jin Kim,et al.  Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system. , 2015, Biomaterials.

[62]  S. Tay,et al.  Microfluidic cell culture. , 2014, Current opinion in biotechnology.

[63]  B. Basu.  Biomaterials for Musculoskeletal Regeneration: Concepts , 2017 .

[64]  Ferdinand le Noble,et al.  What determines blood vessel structure? Genetic prespecification vs. hemodynamics. , 2006, Physiology.

[65]  Michael Levin,et al.  Left–right asymmetry in embryonic development: a comprehensive review , 2005, Mechanisms of Development.

[66]  S. Quake,et al.  Versatile, fully automated, microfluidic cell culture system. , 2007, Analytical chemistry.

[67]  Stefano Piccolo,et al.  Transduction of mechanical and cytoskeletal cues by YAP and TAZ , 2012, Nature Reviews Molecular Cell Biology.

[68]  Chih-Ming Ho,et al.  DNA Diagnostics: Nanotechnology-Enhanced Electrochemical Detection of Nucleic Acids , 2010, Pediatric Research.

[69]  S. Ostrovidov,et al.  Stretchable and micropatterned membrane for osteogenic differentation of stem cells. , 2014, ACS applied materials & interfaces.

[70]  Jina Ko,et al.  Smartphone-enabled optofluidic exosome diagnostic for concussion recovery , 2016, Scientific Reports.

[71]  Ronan M. T. Fleming,et al.  Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices. , 2015, Biosensors & bioelectronics.

[72]  Michael T Longaker,et al.  Regenerative medicine. , 2011, Current problems in surgery.

[73]  J. Rossant,et al.  Cell fate decisions in early blood vessel formation. , 2003, Trends in cardiovascular medicine.

[74]  Jeremy J Mao,et al.  Shear stress induces osteogenic differentiation of human mesenchymal stem cells. , 2010, Regenerative medicine.

[75]  Daniel T Chiu,et al.  A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[76]  Thomas Benjamin,et al.  TAZ, a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation , 2005, Science.

[77]  S. Roberts,et al.  The influence of nutrient supply and cell density on the growth and survival of intervertebral disc cells in 3D culture. , 2011, European cells & materials.

[78]  S. Werner,et al.  Regulation of wound healing by growth factors and cytokines. , 2003, Physiological reviews.

[79]  Sirio Dupont.  Role of YAP/TAZ in mechanotransduction , 2011 .

[80]  Jinfu Wang,et al.  Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress , 2010, Biomechanics and modeling in mechanobiology.

[81]  Wen-I Wu,et al.  Transport of particles and microorganisms in microfluidic channels using rectified ac electro-osmotic flow. , 2011, Biomicrofluidics.

[82]  Hung-Jen Wu,et al.  Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine. , 2017, Lab on a chip.

[83]  C. Siedlecki,et al.  Proteins, platelets, and blood coagulation at biomaterial interfaces. , 2014, Colloids and surfaces. B, Biointerfaces.

[84]  B. Basu,et al.  On The Origin of Shear Stress Induced Myogenesis Using PMMA Based Lab-on-Chip. , 2017, ACS biomaterials science & engineering.

[85]  Ashok Kumar,et al.  Advanced Biomaterials: Fundamentals, Processing, and Applications , 2009 .

[86]  S. Bose,et al.  Synergistic effect of polymorphism, substrate conductivity and electric field stimulation towards enhancing muscle cell growth in vitro , 2016 .

[87]  Kevin J. Staley,et al.  Microfluidics and multielectrode array-compatible organotypic slice culture method , 2009, Journal of Neuroscience Methods.

[88]  D. Irvine,et al.  Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine , 2010, MRS bulletin.

[89]  K. Hotary,et al.  Evidence of a role for endogenous electrical fields in chick embryo development. , 1992, Development.

[90]  W. Blau,et al.  The electrical stimulation of carbon nanotubes to provide a cardiomimetic cue to MSCs. , 2012, Biomaterials.

[91]  Nahm-Gyoo Cho,et al.  A novel microfluidic biosensor based on an electrical detection system for alpha-fetoprotein. , 2008, Biosensors & bioelectronics.

[92]  M. Messerli,et al.  Extracellular Electrical Fields Direct Wound Healing and Regeneration , 2011, The Biological Bulletin.

[93]  B R Ringeisen,et al.  Biochip∕laser cell deposition system to assess polarized axonal growth from single neurons and neuron∕glia pairs in microchannels with novel asymmetrical geometries. , 2011, Biomicrofluidics.

[94]  P. Janmey,et al.  Bone marrow-derived human mesenchymal stem cells become quiescent on soft substrates but remain responsive to chemical or mechanical stimuli. , 2009, Tissue engineering. Part A.

[95]  Ling-Sheng Jang,et al.  Electrical characteristics analysis of various cancer cells using a microfluidic device based on single-cell impedance measurement , 2012 .

[96]  Songhee Jeon,et al.  Sound Waves Induce Neural Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells via Ryanodine Receptor-Induced Calcium Release and Pyk2 Activation , 2016, Applied Biochemistry and Biotechnology.

[97]  Bob S. Carter,et al.  Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma , 2015, Nature Communications.

[98]  Andreas Manz,et al.  Micro total analysis systems: latest achievements. , 2008, Analytical chemistry.

[99]  Beerend P Hierck,et al.  Development‐related changes in the expression of shear stress responsive genes KLF‐2, ET‐1, and NOS‐3 in the developing cardiovascular system of chicken embryos , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[100]  Greeshma Thrivikraman,et al.  Magnetic field assisted stem cell differentiation - role of substrate magnetization in osteogenesis. , 2015, Journal of materials chemistry. B.

[101]  N. Schork.  Personalized medicine: Time for one-person trials , 2015, Nature.