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- Title
An acellular matrix-bound ligand enhances the mobilization, recruitment and therapeutic effects of circulating progenitor cells in a hindlimb ischemia model.
- Authors
Suuronen, Erik J.; Pingchuan Zhang; Kuraitis, Drew; Xudong Cao; Melhuish, Angela; McKee, Daniel; Fengfu Li; Mesana, Thierry G.; Veinot, John P.; Ruel, Marc
- Abstract
Circulating progenitor cells home to and engraft to sites of ischemia, mediated in part by the adhesion molecule L-selectin; however, accumulation in tissues such as the heart is low. In this study, an acellular collagen-based matrix containing sialyl LewisX (sLeX), which binds L-selectin, was developed in order to enhance the endogenous progenitor cell therapeutic response. Its effect on progenitor cells and angiogenesis were assessed in vitro and using a hindlimb ischemia model with rats. In culture, the sLeX collagen matrix recruited more CD133+CD34+L-selectin+ cells than collagen-only matrix, with adhesion mediated by L-selectin binding. Increased angiogenic/chemotactic cytokine production and improved resistance to apoptosis appeared in cells cultured on sLeX-collagen matrix. In vivo, mobilization of endogenous circulating progenitor cells was increased, and greater recruitment of these and systemically injected human peripheral blood CXCR4+L-selectin+ cells to sLeX-collagen treated limbs was observed compared to collagen-only. This condition was associated with differences in angiogenic/chemotactic cytokine levels, with greater arteriole density and increased perfusion in sLeX-collagen treated hindlimbs. With these factors taken together, we demonstrated that an acellular matrix-bound ligand approach can enhance the mobilization, recruitment, and therapeutic effects of endogenous and/or transplanted progenitor cells, possibly through paracrine and antiapoptotic mechanisms, and could be used to improve cell-based regenerative therapies.
- Subjects
LIGANDS (Biochemistry); ISCHEMIA; HINDLIMB; CELL adhesion molecules; LABORATORY rats; REGENERATIVE medicine
- Publication
FASEB Journal, 2009, Vol 23, Issue 5, p1447
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.08-111054