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Tissue engineered cardiac stem cell grafts for repairing heart with myocardial infarction
Author(s) -
Kim DeokHo,
Smith Rachel,
Gupta Kshitiz,
Kim Pilnam,
Suh KahpYang,
Marban Eduardo,
Levchenko Andre
Publication year - 2010
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/fasebj.24.1_supplement.599.11
Subject(s) - stem cell , myocardial infarction , transplantation , regeneration (biology) , in vivo , microbiology and biotechnology , mesenchymal stem cell , myocyte , cardiology , chemistry , medicine , biology
Recently, putative adult cardiac stems cells have been isolated and investigated in the laboratory and clinical settings. In spite of demonstrated repair potential, the utility of transplantation of these cells remains in doubt due to high cell mortality and low tissue integration. Here we demonstrate that the scalable (>1 cm 2 ) nanostructured scaffold of biocompatible hydrogels can produce structurally aligned cardiac stem cell sheets, which mimic the aligned cardiophysiological architecture seen in normal heart tissue in vivo. Through in vitro characterization, we also demonstrate that topographically‐controlled cardiac stem cells grown on the scaffolds show significant increase in cell adhesion, migration, and proliferation compared to the control group. Furthermore, in vitro co‐culture of neonatal rat ventricular myocytes with lentivirally transduced cardiac stem cells expressing NCX promoter‐GFP exhibited enhanced cardiac differentiation on nanofabricated scaffolds. To test the therapeutic potential in vivo, we engrafted the monolayered cardiac stem cell patches onto the infarcted heart of adult rats. We found that engrafted GFP‐labelled cardiac stem cells migrated into and integrated with host cardiac tissue. This was evidenced by formation of stable gap junctions and expression of the cardiac specific marker Troponin I. There was a clear improvement in tissue repair as indicated by thicker infarct walls in those animals that received the stem cell graft. Overall, we argue that our method not only enables development of functional cardiac grafts, but also provides a novel therapeutic approach to promote cardiac regeneration and improve healing in a rat myocardial infarction model.