title: Parthenogenetic stem cells for tissue-engineered heart repair.
abstract: Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.
authors: Institute of Pharmacology, University Medical Center Göttingen, Göttingen, Germany.
authors: Michael
authors: M
authors: Didié
authors: Peter
authors: P
authors: Christalla
authors: Michael
authors: M
authors: Rubart
authors: Vijayakumar
authors: V
authors: Muppala
authors: Stephan
authors: S
authors: Döker
authors: Bernhard
authors: B
authors: Unsöld
authors: Ali
authors: A
authors: El-Armouche
authors: Thomas
authors: T
authors: Rau
authors: Thomas
authors: T
authors: Eschenhagen
authors: Alexander P
authors: AP
authors: Schwoerer
authors: Heimo
authors: H
authors: Ehmke
authors: Udo
authors: U
authors: Schumacher
authors: Sigrid
authors: S
authors: Fuchs
authors: Claudia
authors: C
authors: Lange
authors: Alexander
authors: A
authors: Becker
authors: Wen
authors: W
authors: Tao
authors: John A
authors: JA
authors: Scherschel
authors: Mark H
authors: MH
authors: Soonpaa
authors: Tao
authors: T
authors: Yang
authors: Qiong
authors: Q
authors: Lin
authors: Martin
authors: M
authors: Zenke
authors: Dong-Wook
authors: DW
authors: Han
authors: Hans R
authors: HR
authors: Schöler
authors: Cornelia
authors: C
authors: Rudolph
authors: Doris
authors: D
authors: Steinemann
authors: Brigitte
authors: B
authors: Schlegelberger
authors: Steve
authors: S
authors: Kattman
authors: Alec
authors: A
authors: Witty
authors: Gordon
authors: G
authors: Keller
authors: Loren J
authors: LJ
authors: Field
authors: Wolfram-Hubertus
authors: WH
authors: Zimmermann
mesh_terms: D000200:Action Potentials; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation; D048430:Cell Shape; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D044127:Epigenesis, Genetic; D005838:Genotype; D006321:Heart / Q000502:physiology*; D006648:Histocompatibility / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D009924:Organ Culture Techniques; D009940:Organoids / Q000637:transplantation; D010312:Parthenogenesis; D010641:Phenotype; D033581:Stem Cell Transplantation; D023822:Tissue Engineering; D014184:Transplantation, Homologous
chemical_list: D000943:Antigens, Differentiation; D000949:Histocompatibility Antigens Class II