title: Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium.
abstract: Cellular cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which is the most promising cell source. Therefore, we investigated and examined the fate and functional impact of bone marrow (BM) cells and embryonic stem cell (ES cell)-derived cardiomyocytes after transplantation into the infarcted mouse heart. This proved particularly challenging for the ES cells, as their enrichment into cardiomyocytes and their long-term engraftment and tumorigenicity are still poorly understood. We generated transgenic ES cells expressing puromycin resistance and enhanced green fluorescent protein cassettes under control of a cardiac-specific promoter. Puromycin selection resulted in a highly purified (>99%) cardiomyocyte population, and the yield of cardiomyocytes increased 6-10-fold because of induction of proliferation on purification. Long-term engraftment (4-5 months) was observed when co-transplanting selected ES cell-derived cardiomyocytes and fibroblasts into the injured heart of syngeneic mice, and no teratoma formation was found (n = 60). Although transplantation of ES cell-derived cardiomyocytes improved heart function, BM cells had no positive effects. Furthermore, no contribution of BM cells to cardiac, endothelial, or smooth muscle neogenesis was detected. Hence, our results demonstrate that ES-based cell therapy is a promising approach for the treatment of impaired myocardial function and provides better results than BM-derived cells.
authors.affiliation: Axiogenesis AG, 50931 Cologne, Germany. eugen.kolossov@axiogenesis.com
authors.forename: Eugen
authors.initials: E
authors.lastname: Kolossov
authors.forename: Toktam
authors.initials: T
authors.lastname: Bostani
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Roell
authors.forename: Martin
authors.initials: M
authors.lastname: Breitbach
authors.forename: Frank
authors.initials: F
authors.lastname: Pillekamp
authors.forename: Jens M
authors.initials: JM
authors.lastname: Nygren
authors.forename: Philipp
authors.initials: P
authors.lastname: Sasse
authors.forename: Olga
authors.initials: O
authors.lastname: Rubenchik
authors.forename: Jochen W U
authors.initials: JW
authors.lastname: Fries
authors.forename: Daniela
authors.initials: D
authors.lastname: Wenzel
authors.forename: Caroline
authors.initials: C
authors.lastname: Geisen
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
authors.forename: Zhongju
authors.initials: Z
authors.lastname: Lu
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Duan
authors.forename: Ralf
authors.initials: R
authors.lastname: Kettenhofen
authors.forename: Stefan
authors.initials: S
authors.lastname: Jovinge
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Heribert
authors.initials: H
authors.lastname: Bohlen
authors.forename: Armin
authors.initials: A
authors.lastname: Welz
authors.forename: Juergen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Sten Eirik
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: Bernd K
authors.initials: BK
authors.lastname: Fleischmann
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D017931:DNA Primers; D004594:Electrophysiology; D053595:Embryonic Stem Cells / Q000166:cytology*; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation*; D011691:Puromycin; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011691:Puromycin