Elizabeth C Stucky1, Rene S Schloss2, Martin L Yarmush3, David I Shreiber4. 1. Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA. 2. Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA. 3. Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA; Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA; Center for Engineering in Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: yarmush@rci.rutgers.edu. 4. Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA. Electronic address: shreiber@rci.rutgers.edu.
Abstract
BACKGROUND AIMS: Modulation of inflammation after brain trauma is a key therapeutic goal aimed at limiting the consequences of the subsequent injury cascade. Mesenchymal stromal cells (MSCs) have been demonstrated to dynamically regulate the inflammatory environment in several tissue systems, including the central nervous system. There has been limited success, however, with the use of direct implantation of cells in the brain caused by low viability and engraftment at the injury site. To circumvent this, we encapsulated MSCs in alginate microspheres and evaluated the ability of these encapsulated MSCs to attenuate inflammation in rat organotypic hippocampal slice cultures (OHSC). METHODS: OHSC were administered lipopolysaccharide to induce inflammation and immediately co-cultured with encapsulated or monolayer human MSCs. After 24 h, culture media was assayed for the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) produced by OHSC, as well as MSC-produced trophic mediators. RESULTS: Encapsulated MSCs reduced TNF-α more effectively than did monolayer MSCs. Additionally, there was a strong correlation between increased prostaglandin E2 (PGE2) and reduction of TNF-α. In contrast to monolayer MSCs, inflammatory signals were not required to stimulate PGE2 production by encapsulated MSCs. Further encapsulation-stimulated changes were revealed in a multiplex panel analyzing 27 MSC-produced cytokines and growth factors, from which additional mediators with strong correlations to TNF-α levels were identified. CONCLUSIONS: These results suggest that alginate encapsulation of MSCs may not only provide an improved delivery vehicle for transplantation but may also enhance MSC therapeutic benefit for treating neuro-inflammation.
BACKGROUND AIMS: Modulation of inflammation after brain trauma is a key therapeutic goal aimed at limiting the consequences of the subsequent injury cascade. Mesenchymal stromal cells (MSCs) have been demonstrated to dynamically regulate the inflammatory environment in several tissue systems, including the central nervous system. There has been limited success, however, with the use of direct implantation of cells in the brain caused by low viability and engraftment at the injury site. To circumvent this, we encapsulated MSCs in alginate microspheres and evaluated the ability of these encapsulated MSCs to attenuate inflammation in rat organotypic hippocampal slice cultures (OHSC). METHODS:OHSC were administered lipopolysaccharide to induce inflammation and immediately co-cultured with encapsulated or monolayer human MSCs. After 24 h, culture media was assayed for the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) produced by OHSC, as well as MSC-produced trophic mediators. RESULTS: Encapsulated MSCs reduced TNF-α more effectively than did monolayer MSCs. Additionally, there was a strong correlation between increased prostaglandin E2 (PGE2) and reduction of TNF-α. In contrast to monolayer MSCs, inflammatory signals were not required to stimulate PGE2 production by encapsulated MSCs. Further encapsulation-stimulated changes were revealed in a multiplex panel analyzing 27 MSC-produced cytokines and growth factors, from which additional mediators with strong correlations to TNF-α levels were identified. CONCLUSIONS: These results suggest that alginate encapsulation of MSCs may not only provide an improved delivery vehicle for transplantation but may also enhance MSC therapeutic benefit for treating neuro-inflammation.
Authors: Ashley M Fenn; John P Skendelas; Daniel N Moussa; Megan M Muccigrosso; Phillip G Popovich; Jonathan Lifshitz; Daniel S Eiferman; Jonathan P Godbout Journal: J Neurotrauma Date: 2014-11-13 Impact factor: 5.269
Authors: Evelyn Kendall Williams; José R García; Robert G Mannino; Rebecca S Schneider; Wilbur A Lam; Andrés J García Journal: Integr Biol (Camb) Date: 2019-04-01 Impact factor: 2.192
Authors: Robert A Pouliot; Patrick A Link; Nabil S Mikhaiel; Matthew B Schneck; Michael S Valentine; Franck J Kamga Gninzeko; Joseph A Herbert; Masahiro Sakagami; Rebecca L Heise Journal: J Biomed Mater Res A Date: 2016-04-06 Impact factor: 4.396
Authors: Bjarke Follin; Morten Juhl; Smadar Cohen; Anders Elm Pedersen; Jens Kastrup; Annette Ekblond Journal: Tissue Eng Part B Rev Date: 2016-03-16 Impact factor: 6.389
Authors: Jesús Ciriza; Laura Saenz Del Burgo; Haritz Gurruchaga; Francesc E Borras; Marcella Franquesa; Gorka Orive; Rosa Maria Hernández; José Luis Pedraz Journal: Drug Deliv Date: 2018-11 Impact factor: 6.419