title: Injectable PLGA porous beads cellularized by hAFSCs for cellular cardiomyoplasty.
abstract: Cellular cardiomyoplasty has been limited by poor graft retention after cell transplantation. To ensure good retention of the engrafted cells, a microfluidic device was used to fabricate spherical porous beads of poly(D,L-lactic-co-glycolic acid) as a platform for cell delivery. The beads thus obtained had a relatively uniform size, a highly porous structure, and a favorably interconnected interior architecture, to facilitate the transportation of oxygen and nutrients. These porous beads were loaded with human amniotic fluid stem cells (hAFSCs) to generate cellularized microscaffolds. Live/dead assay demonstrated that most of the cells in the porous constructs were viable. The hAFSCs that were grown in beads formed a complex three-dimensional organization with well-preserved extracellular matrices (ECM) according to their porous structure. Retention of the administered beads was clearly identified at the site of engraftment following an experimentally induced myocardial infarction in a rat model. The results of echocardiography, magnetic resonance imaging, and histological analyses suggest that the transplantation of hAFSC beads into an infarcted heart could effectively maintain its gross morphology, prevent successive ventricular expansion, and thereby improve the post-infarcted cardiac function. Immunofluorescent staining revealed that the microenvironment that was provided by the infarcted myocardium might offer cues for the induction of the engrafted hAFSCs into angiogenic and cardiomyogenic lineages. Our results demonstrate that the cellularized beads with endogenously secreted ECM were of sufficient physical size to be entrapped in the interstitial tissues following transplantation, thereby benefiting the infarcted heart.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
authors.forename: Chieh-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Hao-Ji
authors.initials: HJ
authors.lastname: Wei
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Yeh
authors.forename: Jiun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Lin
authors.forename: Ting-Yin
authors.initials: TY
authors.lastname: Lee
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Choi
authors.forename: Younan
authors.initials: Y
authors.lastname: Xia
authors.forename: Yen
authors.initials: Y
authors.lastname: Chang
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000818:Animals; D018421:Cardiomyoplasty / Q000379:methods*; D004452:Echocardiography; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008855:Microscopy, Electron, Scanning; D009203:Myocardial Infarction / Q000628:therapy; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid