title: Tumourigenesis in the infarcted rat heart is eliminated through differentiation and enrichment of the transplanted embryonic stem cells.
abstract: OBJECTIVE
  The therapeutic potential of embryonic stem cells (ESCs) in ischaemic heart disease has been widely explored. However, tumourigenesis upon implantation interferes with the clinical application of ESC transplantation. This study aims to evaluate the influence of differentiation and enrichment of transplanted ESCs on tumourigenesis in infarcted rat hearts.
  
  
  RESULTS
  Mouse ESCs (mESCs) were cultured using a bioreactor system to develop embryoid bodies, which were then induced with 1% ascorbic acid to differentiate into cardiomyocytes. The mESCs-derived cardiomyocytes (mESCs-CMs) were enriched by Percoll density gradient separation. The specific markers (OCT-4, Sox2, and Nanog) of undifferentiated ESCs were detected by PCR both in mESCs and in mESCs-CMs, but not in the mESC-derived Percoll-enriched cardiomyocytes (mESC-PE-CMs). Immunosuppressed rats with infarcted hearts were randomly injected with the mESCs, mESC-CMs, or mESC-PE-CMs. Eight weeks after cell transplantation, histological and immunohistochemical analysis showed that the transplantation of both mESCs and mESC-CMs caused the formation of teratomas. The incidence of teratoma was markedly lower (P < 0.05) in the mESC-CMs group than in the mESCs group. The average tumour volume was significantly lower (P < 0.05) in the mESC-CMs group than in the mESCs group. Tumour formation was absent in the mESC-PE-CMs group.
  
  
  CONCLUSIONS
  Enrichment of the mESC-differentiated cardiomyocytes inhibited the development of teratoma after cell transplantation in the infarcted rat hearts. These findings offer a new strategy for eliminating teratoma formation in ESCs transplantation and could be a step forward in the development of human ESCs transplantation therapy in ischaemic heart disease.
authors.affiliation: Department of Tissue Engineering, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Road, Beijing, People's Republic of China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Lin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Cuimi
authors.initials: C
authors.lastname: Duan
authors.forename: Yanmeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Kuiwu
authors.initials: K
authors.lastname: Wu
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002499:Centrifugation, Density Gradient; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005260:Female; D006338:Heart Neoplasms / Q000517:prevention & control*; D007150:Immunohistochemistry; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy*; D017202:Myocardial Ischemia / Q000601:surgery; D032383:Myocytes, Cardiac / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013724:Teratoma / Q000517:prevention & control*