Abstract
Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell-cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as 'synthetic stem cells' which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biomimetic Materials / chemistry
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Biomimetic Materials / metabolism
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Biomimetic Materials / pharmacology*
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Cell Fractionation
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Cell Membrane / chemistry
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Cell Membrane / metabolism*
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Cell Membrane / transplantation
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Cell-Derived Microparticles / chemistry
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Cell-Derived Microparticles / metabolism*
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Cell-Derived Microparticles / transplantation
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Culture Media, Conditioned / chemistry*
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Culture Media, Conditioned / isolation & purification
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Disease Models, Animal
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Gene Expression
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Hepatocyte Growth Factor / genetics
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Hepatocyte Growth Factor / metabolism
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Humans
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Injections, Intralesional
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / metabolism
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Intercellular Signaling Peptides and Proteins / pharmacology
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Male
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Mice
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Myocardial Infarction / metabolism
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Myocardial Infarction / pathology
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Myocardial Infarction / therapy*
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Myocardium / metabolism
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Myocardium / pathology
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Paracrine Communication
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Recovery of Function / drug effects
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Stem Cells / cytology
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Stem Cells / metabolism*
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Culture Media, Conditioned
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HGF protein, mouse
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Intercellular Signaling Peptides and Proteins
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Vascular Endothelial Growth Factor A
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insulin-like growth factor-1, mouse
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vascular endothelial growth factor A, mouse
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Hepatocyte Growth Factor
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Insulin-Like Growth Factor I