Enhanced engraftment and repairing ability of human adipose-derived stem cells, conveyed by pharmacologically active microcarriers continuously releasing HGF and IGF-1, in healing myocardial infarction in rats.
One of the main cause of ineffective cell therapy in repairing the damaged heart is the poor yield of grafted cells. To overcome this drawback, rats with 4-week-old myocardial infarction (MI) were injected in the border zone with human adipose-derived stem cells (ADSCs) conveyed by poly(lactic-co-glycolic acid) microcarriers (PAMs) releasing hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) (GFsPAMs). According to treatments, animals were subdivided into different groups: MI_ADSC, MI_ADSC/PAM, MI_GFsPAM, MI_ADSC/GFsPAM, and untreated MI_V. Two weeks after injection, a 31% increase in ADSC engraftment was observed in MI_ADSC/PAM compared with MI_ADSC (p < 0.05). A further ADSC retention was obtained in MI_ADSC/GFsPAM with respect to MI_ADSC (106%, p < 0.05) and MI_ADSC/PAM (57%, p < 0.05). A 130% higher density of blood vessels of medium size was present in MI_ADSC/GFsPAM compared with MI_ADSC (p < 0.01). MI_ADSC/GFsPAM also improved, albeit slightly, left ventricular remodeling and hemodynamics with respect to the other groups. Notably, ADSCs and/or PAMs, with or without HGF/IGF-1, trended to induce arrhythmias in electrically driven, Langendorff-perfused, hearts of all groups. Thus, PAMs releasing HGF/IGF-1 markedly increase ADSC engraftment 2 weeks after injection and stimulate healing in chronically infarcted myocardium, but attention should be paid to potentially negative electrophysiological consequences.
Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/A, 43124, Parma, Italy.
Monia
M
Savi
Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/A, 43124, Parma, Italy.
Leonardo
L
Bocchi
National Institute for Cardiovascular Research, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy.
Emanuela
E
Fiumana
Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy.|UMR S-1066 F-49933, LUNAM University, Angers, France.|INSERM U1066, MINT "Micro Et Nanomédecines Biomimétiques" F-49933, Angers, France.
Jean-Pierre
JP
Karam
Department of Clinical and Experimental Medicine, University of Parma, Via A. Gramsci 14, 43126, Parma, Italy.
Caterina
C
Frati
National Institute for Cardiovascular Research, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy.
Francesca
F
Bonafé
Department of Clinical and Experimental Medicine, University of Parma, Via A. Gramsci 14, 43126, Parma, Italy.
Stefano
S
Cavalli
Department of Specialist, Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy.
Paolo G
PG
Morselli
National Institute for Cardiovascular Research, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy.
Carlo
C
Guarnieri
National Institute for Cardiovascular Research, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy.
Claudio M
CM
Caldarera
National Institute for Cardiovascular Research, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy.
Claudio
C
Muscari
UMR S-1066 F-49933, LUNAM University, Angers, France.|INSERM U1066, MINT "Micro Et Nanomédecines Biomimétiques" F-49933, Angers, France.
Claudia N
CN
Montero-Menei
Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/A, 43124, Parma, Italy.|National Institute for Cardiovascular Research, Bologna, Italy.
Donatella
D
Stilli
National Institute for Cardiovascular Research, Bologna, Italy.|Department of Clinical and Experimental Medicine, University of Parma, Via A. Gramsci 14, 43126, Parma, Italy.
Federico
F
Quaini
Department of Life Sciences, University of Parma, Parco Area delle Scienze 11/A, 43124, Parma, Italy.|National Institute for Cardiovascular Research, Bologna, Italy.
Ezio
E
Musso
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D040761:Biomimetic Materials / Q000737:chemistry; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D019344:Lactic Acid; D008297:Male; D008422:Materials Testing; D008863:Microspheres; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D020257:Ventricular Remodeling; D014945:Wound Healing / Q000187:drug effects
D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I
adipose-derived stem cell; arrhythmia; hepatocyte growth factor; insulin-like growth factor 1; myocardial infarction; pharmacologically active microcarrier