title: Functional performance of human cardiosphere-derived cells delivered in an in situ polymerizable hyaluronan-gelatin hydrogel.
abstract: The vast majority of cells delivered into the heart by conventional means are lost within the first 24 h. Methods are needed to enhance cell retention, so as to minimize loss of precious material and maximize effectiveness of the therapy. We tested a cell-hydrogel delivery strategy. Cardiosphere-derived cells (CDCs) were grown from adult human cardiac biopsy specimens. In situ polymerizable hydrogels made of hyaluronan and porcine gelatin (Hystem(®)-C™) were formulated as a liquid at room temperature so as to gel within 20 min at 37 °C. CDC viability and migration were not compromised in Hystem-C™. Myocardial infarction was created in SCID mice and CDCs were injected intramyocardially in the infarct border zone. Real-time PCR revealed engraftment of CDCs delivered in Hystem-C™ was increased by nearly an order of magnitude. LVEF (left ventricular ejection fraction) deteriorated in the control (PBS only) group over the 3-week time course. Hystem-C™ alone or CDCs alone preserved LVEF relative to baseline, while CDCs delivered in Hystem-C™ resulted in a sizable boost in LVEF. Heart morphometry revealed the greatest attenuation of LV remodeling in the CDC + Hystem-C™ group. Histological analysis suggested cardiovascular differentiation of the CDCs in Hystem-C™. However, the majority of functional benefit is likely from paracrine mechanisms such as tissue preservation and neovascularization. A CDC/hydrogel formulation suitable for catheter-based intramyocardial injection exhibits superior engraftment and functional benefits relative to naked CDCs.
authors.affiliation: The Cedars-Sinai Heart Institute, Los Angeles, CA 90048, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Blusztajn
authors.forename: Deliang
authors.initials: D
authors.lastname: Shen
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.forename: Baiming
authors.initials: B
authors.lastname: Sun
authors.forename: Giselle
authors.initials: G
authors.lastname: Galang
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Zarembinski
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Smith
authors.forename: Linda
authors.initials: L
authors.lastname: Marbán
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005780:Gelatin / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D058105:Polymerization / Q000187:drug effects*; D018874:Spheroids, Cellular / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation*; D014021:Tissue Preservation
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin; D006820:Hyaluronic Acid