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A novel electro-chemotactic approach to impact the directional migration of transplantable retinal progenitor cells.
Exp Eye Res 2019; 185:107688EE

Abstract

Photoreceptor degeneration is a significant cause of visual impairment in the United States and globally. Cell replacement therapy shows great promise in restoring vision by transplanting stem-like cells into the sub-retinal space as substitutes for damaged photoreceptors. However, vision repair via transplantation has been limited, in large part, by low numbers of replacement cells able to migrate into damaged retinal tissue and integrate with native photoreceptors. Projects have used external chemical fields and applied electric fields to induce the chemotaxis and electrotaxis of replacement cells, respectively, with limited success. However, the application of combined electro-chemotactic fields in directing cells within biomaterials and host tissue has been surprisingly understudied. The current work examined the ability of combined electro-chemotactic fields to direct the migration of transplantable retinal progenitor cells (RPCs) in controlled microenvironments. Experiments used our established galvano-microfluidic system (Gal-MμS) to generate tunable chemotactic concentration fields with and without superimposed electric fields. Result illustrate that combination fields increased the distance migrated by RPCs by over three times that seen in either field, individually, and with greater directionality towards increasing gradients. Interestingly, immunofluorescence assays showed no significant differences in the distribution of the total and/or activated cognate receptor of interest, indicating that changes in ligand binding alone were not responsible for the measured increases in migration. Bioinformatics analysis was then performed to identity potential, synergistic mechanistic pathways involved in the electro-chemotaxis measured. Results indicate that increased RPC migration in electro-chemotactic fields may arise from down-regulation of cell adhesion proteins in tandem with up-regulation of cytoskeletal regulation proteins. These comprehensive results point towards a novel migration-targeted treatment that may dramatically improve transplantation outcomes as well as elucidate unreported synergy across biological mechanisms in response to electro-chemotactic fields.

Authors+Show Affiliations

Nix Biosensors, Boston, MA, USA. Electronic address: smishra000@citymail.cuny.edu.Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.Department of Biology, Lehman College, New York, NY, USA.Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA. Electronic address: Maribel.Vazquez@rutgers.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31185219

Citation

Mishra, Shawn, et al. "A Novel Electro-chemotactic Approach to Impact the Directional Migration of Transplantable Retinal Progenitor Cells." Experimental Eye Research, vol. 185, 2019, p. 107688.
Mishra S, Peña JS, Redenti S, et al. A novel electro-chemotactic approach to impact the directional migration of transplantable retinal progenitor cells. Exp Eye Res. 2019;185:107688.
Mishra, S., Peña, J. S., Redenti, S., & Vazquez, M. (2019). A novel electro-chemotactic approach to impact the directional migration of transplantable retinal progenitor cells. Experimental Eye Research, 185, p. 107688. doi:10.1016/j.exer.2019.06.002.
Mishra S, et al. A Novel Electro-chemotactic Approach to Impact the Directional Migration of Transplantable Retinal Progenitor Cells. Exp Eye Res. 2019;185:107688. PubMed PMID: 31185219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel electro-chemotactic approach to impact the directional migration of transplantable retinal progenitor cells. AU - Mishra,Shawn, AU - Peña,Juan S, AU - Redenti,Stephen, AU - Vazquez,Maribel, Y1 - 2019/06/08/ PY - 2019/02/06/received PY - 2019/06/02/revised PY - 2019/06/04/accepted PY - 2020/08/01/pmc-release PY - 2019/6/12/pubmed PY - 2019/6/12/medline PY - 2019/6/12/entrez KW - Bioinformatics KW - Chemotaxis KW - Microfluidics KW - Retinal progenitor cells KW - Transplantation SP - 107688 EP - 107688 JF - Experimental eye research JO - Exp. Eye Res. VL - 185 N2 - Photoreceptor degeneration is a significant cause of visual impairment in the United States and globally. Cell replacement therapy shows great promise in restoring vision by transplanting stem-like cells into the sub-retinal space as substitutes for damaged photoreceptors. However, vision repair via transplantation has been limited, in large part, by low numbers of replacement cells able to migrate into damaged retinal tissue and integrate with native photoreceptors. Projects have used external chemical fields and applied electric fields to induce the chemotaxis and electrotaxis of replacement cells, respectively, with limited success. However, the application of combined electro-chemotactic fields in directing cells within biomaterials and host tissue has been surprisingly understudied. The current work examined the ability of combined electro-chemotactic fields to direct the migration of transplantable retinal progenitor cells (RPCs) in controlled microenvironments. Experiments used our established galvano-microfluidic system (Gal-MμS) to generate tunable chemotactic concentration fields with and without superimposed electric fields. Result illustrate that combination fields increased the distance migrated by RPCs by over three times that seen in either field, individually, and with greater directionality towards increasing gradients. Interestingly, immunofluorescence assays showed no significant differences in the distribution of the total and/or activated cognate receptor of interest, indicating that changes in ligand binding alone were not responsible for the measured increases in migration. Bioinformatics analysis was then performed to identity potential, synergistic mechanistic pathways involved in the electro-chemotaxis measured. Results indicate that increased RPC migration in electro-chemotactic fields may arise from down-regulation of cell adhesion proteins in tandem with up-regulation of cytoskeletal regulation proteins. These comprehensive results point towards a novel migration-targeted treatment that may dramatically improve transplantation outcomes as well as elucidate unreported synergy across biological mechanisms in response to electro-chemotactic fields. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/31185219/A_novel_electro-chemotactic_approach_to_impact_the_directional_migration_of_transplantable_retinal_progenitor_cells L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(19)30068-5 DB - PRIME DP - Unbound Medicine ER -