Single-cell hydrogel encapsulation for enhanced survival of human marrow stromal cells

Abstract Inadequate extracellular matrix cues and subsequent apoptotic cell death are among crucial factors currently limiting cell viability and organ retention in cell-based therapeutic strategies for vascular regeneration. Here we describe the use of a single-cell hydrogel capsule to provide enha...

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Bibliographic Details
Published in:Biomaterials 2009-10, Vol.30 (29), p.5445-5455
Main Authors: Karoubi, Golnaz, Ormiston, Mark L, Stewart, Duncan J, Courtman, David W
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Anoikis
Cell Culture Techniques - methods
Cell Survival
Cell therapy
Cells, Cultured
Dentistry
Encapsulation
Humans
Hydrogel
Hydrogels - chemistry
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - physiology
Myocardial ischemia
Peripheral vascular disease
Rats
Rats, Inbred F344
Sepharose - chemistry
Tissue Engineering - methods
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Summary:Abstract Inadequate extracellular matrix cues and subsequent apoptotic cell death are among crucial factors currently limiting cell viability and organ retention in cell-based therapeutic strategies for vascular regeneration. Here we describe the use of a single-cell hydrogel capsule to provide enhanced cell survival of adherent cells in transient suspension culture. Human marrow stromal cells (hMSCs) were singularly encapsulated in agarose capsules containing the immobilized matrix molecules, fibronectin and fibrinogen to ameliorate cell-matrix survival signals. MSCs in the enriched capsules demonstrated increased viability, greater metabolic activity and enhanced cell-cytoskeletal patterning. Increased cell viability resulted from the re-induction of cell-matrix interactions likely via integrin clustering and subsequent activation of the extracellular signal regulated MAPK (ERK)/mitogen activated protein kinase (MAPK) signaling cascade. Proof of principle in-vivo studies, investigating autologous MSC delivery into Fisher 344 rat hindlimb, depicted a significant increase in the number of engrafted cells using the single-cell encapsulation system. Incorporation of immobilized adhesion molecules compensates, at least in part, for the missing cell-matrix cues, thereby attenuating the initial anoikis stimuli and providing protection from subsequent apoptosis. Thus, this single-cell encapsulation strategy may markedly enhance therapeutic cell survival in targeted tissues.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2009.06.035