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An acellular matrix‐bound ligand enhances the mobilization, recruitment and therapeutic effects of circulating progenitor cells in a hindlimb ischemia model
Author(s) -
Suuronen Erik J.,
Zhang Pingchuan,
Kuraitis Drew,
Cao Xudong,
Melhuish Angela,
McKee Daniel,
Li Fengfu,
Mesana Thierry G.,
Veinot John P.,
Ruel Marc
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-111054
Subject(s) - progenitor cell , angiogenesis , microbiology and biotechnology , endothelial progenitor cell , paracrine signalling , immunology , extracellular matrix , homing (biology) , stem cell , chemistry , cancer research , medicine , biology , receptor , ecology
Circulating progenitor cells home to and engraft to sites of ischemia, mediated in part by the adhesion molecule Lrselectin; however, accumulation in tissues such as the heart is low. In this study, an acellular collagen‐based matrix containing sialyl Lewis X (sLe X ), 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 sLe X – collagen matrix recruited more CD133 + CD34 + L‐selectm + 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 sLe X ‐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 sLe X ‐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 sLe X ‐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.— Suuronen, E. J., Zhang, P., Kuraitis, D., Cao, X., Melhuish, A., McKee, D., Li, F., Mesana, T. G., Veinot, J. P., Ruel, M. An acellular matrix‐bound ligand enhances the mobilization, recruitment and therapeutic effects of circulating progenitor cells in a hindlimb ischemia model. FASEBJ. 23, 1447–1458 (2009)