title: Alginate micro-encapsulation of mesenchymal stromal cells enhances modulation of the neuro-inflammatory response.
abstract: OBJECTIVE
  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.affiliation: Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Stucky
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
authors.forename: Rene S
authors.initials: RS
authors.lastname: Schloss
authors.affiliation: 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.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Yarmush
authors.affiliation: Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA. Electronic address: shreiber@rci.rutgers.edu.
authors.forename: David I
authors.initials: DI
authors.lastname: Shreiber
mesh_terms: D000328:Adult; D000464:Alginates; D000818:Animals; D001930:Brain Injuries / Q000601:surgery*; D002214:Capsules; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D007249:Inflammation / Q000601:surgery*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D020723:Glucuronic Acid; D015232:Dinoprostone
keywords: co-culture; inflammation mediators; mesenchymal stromal cells; organ culture; traumatic brain injury