Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System
Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transpla...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-10-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/8/10/1301 |
| _version_ | 1827847270458982400 |
|---|---|
| author | Caroline D. Pena Stephanie Zhang Robert Majeska Tadmiri Venkatesh Maribel Vazquez |
| author_facet | Caroline D. Pena Stephanie Zhang Robert Majeska Tadmiri Venkatesh Maribel Vazquez |
| author_sort | Caroline D. Pena |
| collection | DOAJ |
| description | Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insufficient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to our understanding of retinogenesis and the development of effective, cell-based approaches to retinal replacement. The current article describes a new bio-engineering approach to investigate the migratory responses of innate collections of RPCs upon extracellular substrates by combining microfluidics with the well-established invertebrate model of <i>Drosophila melanogaster</i>. Experiments utilized microfluidics to investigate how the composition, size, and adhesion of RPC clusters on defined extracellular substrates affected migration to exogenous chemotactic signaling. Results demonstrated that retinal cluster size and composition influenced RPC clustering upon extracellular substrates of concanavalin (Con-A), Laminin (LM), and poly-L-lysine (PLL), and that RPC cluster size greatly altered collective migratory responses to signaling from Fibroblast Growth Factor (FGF), a primary chemotactic agent in <i>Drosophila</i>. These results highlight the significance of examining collective cell-biomaterial interactions on bio-substrates of emerging biomaterials to aid directional migration of transplanted cells. Our approach further introduces the benefits of pairing genetically controlled models with experimentally controlled microenvironments to advance cell replacement therapies. |
| first_indexed | 2024-03-12T09:28:06Z |
| format | Article |
| id | doaj.art-3f2c600bb31b4df9b335f6fc1af73b99 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T09:28:06Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3f2c600bb31b4df9b335f6fc1af73b992023-09-02T14:02:24ZengMDPI AGCells2073-44092019-10-01810130110.3390/cells8101301cells8101301Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic SystemCaroline D. Pena0Stephanie Zhang1Robert Majeska2Tadmiri Venkatesh3Maribel Vazquez4Department of Biomedical Engineering, City College of New York, New York, NY 10031, USADepartment of Biomedical Engineering, The State University of New York at Binghamton, NY 13902, USADepartment of Biomedical Engineering, City College of New York, New York, NY 10031, USADepartment of Biology, City College of New York, New York, NY 10031, USADepartment of Biomedical Engineering, Rutgers University, The State University of New Jersey, New Brunswick, NJ 08854, USARegenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insufficient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to our understanding of retinogenesis and the development of effective, cell-based approaches to retinal replacement. The current article describes a new bio-engineering approach to investigate the migratory responses of innate collections of RPCs upon extracellular substrates by combining microfluidics with the well-established invertebrate model of <i>Drosophila melanogaster</i>. Experiments utilized microfluidics to investigate how the composition, size, and adhesion of RPC clusters on defined extracellular substrates affected migration to exogenous chemotactic signaling. Results demonstrated that retinal cluster size and composition influenced RPC clustering upon extracellular substrates of concanavalin (Con-A), Laminin (LM), and poly-L-lysine (PLL), and that RPC cluster size greatly altered collective migratory responses to signaling from Fibroblast Growth Factor (FGF), a primary chemotactic agent in <i>Drosophila</i>. These results highlight the significance of examining collective cell-biomaterial interactions on bio-substrates of emerging biomaterials to aid directional migration of transplanted cells. Our approach further introduces the benefits of pairing genetically controlled models with experimentally controlled microenvironments to advance cell replacement therapies.https://www.mdpi.com/2073-4409/8/10/1301<i>drosophila</i>collective migrationneuronsgliafibroblast growth factor |
| spellingShingle | Caroline D. Pena Stephanie Zhang Robert Majeska Tadmiri Venkatesh Maribel Vazquez Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System Cells <i>drosophila</i> collective migration neurons glia fibroblast growth factor |
| title | Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System |
| title_full | Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System |
| title_fullStr | Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System |
| title_full_unstemmed | Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System |
| title_short | Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System |
| title_sort | invertebrate retinal progenitors as regenerative models in a microfluidic system |
| topic | <i>drosophila</i> collective migration neurons glia fibroblast growth factor |
| url | https://www.mdpi.com/2073-4409/8/10/1301 |
| work_keys_str_mv | AT carolinedpena invertebrateretinalprogenitorsasregenerativemodelsinamicrofluidicsystem AT stephaniezhang invertebrateretinalprogenitorsasregenerativemodelsinamicrofluidicsystem AT robertmajeska invertebrateretinalprogenitorsasregenerativemodelsinamicrofluidicsystem AT tadmirivenkatesh invertebrateretinalprogenitorsasregenerativemodelsinamicrofluidicsystem AT maribelvazquez invertebrateretinalprogenitorsasregenerativemodelsinamicrofluidicsystem |