An image J plugin for the high throughput image analysis of in vitro scratch wound healing assays

In vitro scratch wound healing assay, a simple and low-cost technique that works along with other image analysis tools, is one of the most widely used 2D methods to determine the cellular migration and proliferation in processes such as regeneration and disease. There are open-source programs such as imageJ to analyze images of in vitro scratch wound healing assays, but these tools require manual tuning of various parameters, which is time-consuming and limits image throughput. For that reason, we developed an optimized plugin for imageJ to automatically recognize the wound healing size, correct the average wound width by considering its inclination, and quantify other important parameters such as: area, wound area fraction, average wound width, and width deviation of the wound images obtained from a scratch/ wound healing assay. Our plugin is easy to install and can be used with different operating systems. It can be adapted to analyze both individual images and stacks. Additionally, it allows the analysis of images obtained from bright field, phase contrast, and fluorescence microscopes. In conclusion, this new imageJ plugin is a robust tool to automatically standardize and facilitate quantification of different in vitro wound parameters with high accuracy compared with other tools and manual identification.

[1]  S. Oliaei,et al.  Sterilization of PMMA microfluidic chips by various techniques and investigation of material characteristics , 2016 .

[2]  Axel Meyer,et al.  Asymmetric paralog evolution between the “cryptic” gene Bmp16 and its well-studied sister genes Bmp2 and Bmp4 , 2019, Scientific Reports.

[3]  F. De Filippis,et al.  A Selected Core Microbiome Drives the Early Stages of Three Popular Italian Cheese Manufactures , 2014, PloS one.

[4]  Stefan Posch,et al.  Cell migration analysis: Segmenting scratch assay images with level sets and support vector machines , 2012, Pattern Recognit..

[5]  Håvard Jenssen,et al.  Optimized Scratch Assay for In Vitro Testing of Cell Migration with an Automated Optical Camera. , 2018, Journal of visualized experiments : JoVE.

[6]  J. Hornung,et al.  Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line , 1988, The Journal of cell biology.

[7]  Steffen Nyegaard,et al.  An optimized method for accurate quantification of cell migration using human small intestine cells , 2016, Metabolic engineering communications.

[8]  Alissa M. Weaver,et al.  Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin , 2017, The Journal of cell biology.

[9]  Feng Xu,et al.  An introduction to the wound healing assay using live-cell microscopy , 2014, Cell adhesion & migration.

[10]  Johannes E. Schindelin,et al.  The ImageJ ecosystem: An open platform for biomedical image analysis , 2015, Molecular reproduction and development.

[11]  Jan Feijen,et al.  A microfluidic wound-healing assay for quantifying endothelial cell migration. , 2010, American journal of physiology. Heart and circulatory physiology.

[12]  Ali Khademhosseini,et al.  Patient‐Specific Bioinks for 3D Bioprinting of Tissue Engineering Scaffolds , 2018, Advanced healthcare materials.

[13]  You-guang Huang,et al.  Effects of MicroRNA-206 on Osteosarcoma Cell Proliferation, Apoptosis, Migration and Invasion by Targeting ANXA2 Through the AKT Signaling Pathway , 2018, Cellular Physiology and Biochemistry.

[14]  S MacNeil,et al.  Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays. , 2010, Experimental cell research.

[15]  J. Guan,et al.  Wound-healing assay. , 2005, Methods in molecular biology.

[16]  M Fenu,et al.  A novel magnet-based scratch method for standardisation of wound-healing assays , 2019, Scientific Reports.

[17]  S. Ramakrishna,et al.  In vitro skin models and tissue engineering protocols for skin graft applications. , 2016, Essays in biochemistry.

[18]  A. Petrella,et al.  Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway , 2016, Scientific Reports.

[19]  D. Mooney,et al.  Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs. , 2017, Biomaterials.

[20]  Chunmao Han,et al.  Silver nanoparticle loaded collagen/chitosan scaffolds promote wound healing via regulating fibroblast migration and macrophage activation , 2017, Scientific Reports.

[21]  Petros Koumoutsakos,et al.  TScratch: a novel and simple software tool for automated analysis of monolayer wound healing assays. , 2009, BioTechniques.

[22]  Paul Martin,et al.  Wound Healing--Aiming for Perfect Skin Regeneration , 1997, Science.

[23]  A. Shabbir,et al.  Mesenchymal Stem Cell Exosomes Induce Proliferation and Migration of Normal and Chronic Wound Fibroblasts, and Enhance Angiogenesis In Vitro. , 2015, Stem cells and development.

[24]  Tongmin Wang,et al.  ProNGF siRNA inhibits cell proliferation and invasion of pancreatic cancer cells and promotes anoikis. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[25]  P. He,et al.  Real-time monitoring of skin wound healing on nano-grooves topography using electric cell-substrate impedance sensing (ECIS) , 2017 .

[26]  Mohsen Khosravi Maharlooei,et al.  Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats. , 2011, Diabetes research and clinical practice.

[27]  C. Liang,et al.  In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro , 2007, Nature Protocols.

[28]  W. Vandertop,et al.  Effects of sterilization on the mechanical properties of poly(methyl methacrylate) based personalized medical devices. , 2018, Journal of the mechanical behavior of biomedical materials.

[29]  C Venter,et al.  Rapid quantification of cellular proliferation and migration using ImageJ. , 2019, BioTechniques.

[30]  Joachim Wegener,et al.  Electrical wound-healing assay for cells in vitro. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Francisco Prieto-Castrillo,et al.  Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay. , 2017, The Journal of investigative dermatology.

[32]  H. Jun,et al.  Stem Cell Secretome and Its Effect on Cellular Mechanisms Relevant to Wound Healing. , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[33]  A. Pollard,et al.  Limb proportions show developmental plasticity in response to embryo movement , 2017, Scientific Reports.

[34]  Itali Linero,et al.  Paracrine Effect of Mesenchymal Stem Cells Derived from Human Adipose Tissue in Bone Regeneration , 2014, PloS one.

[35]  Sarah A. Snyder,et al.  Electrical Stimulation Increases Random Migration of Human Dermal Fibroblasts , 2017, Annals of Biomedical Engineering.

[36]  K. Myburgh,et al.  In vitro myoblast motility models: investigating migration dynamics for the study of skeletal muscle repair , 2013, Journal of Muscle Research and Cell Motility.

[37]  V. Chandrasekaran,et al.  The effects of energy beverages on cultured cells. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.