title: Marrow stromal cells differentiate into vasculature after allogeneic transplantation into ischemic myocardium.
abstract: BACKGROUND
  Marrow stromal cells (MSCs) are reportedly able to improve ventricular function after myocardial infarction through the paracrine effect or regenerating myocytes. However, the evidence to prove that is scant. In this animal study, we employed MSCs isolated from transgenic pigs designed to express enhanced green fluorescent proteins as the donor to study the fate of the cells after allogeneic transplantation.
  
  
  METHODS
  Green MSCs prepared from transgenic pigs were allogeneically transplanted into chronic ischemic myocardium of 8 Yorkshire pigs by direct intramyocardial injection (total 1.2 × 10(8) cells in 2.5 mL saline, with 25 injection sites). Cohorts of 2 animals were sacrificed at 1, 2, 4, and 6 weeks, and 3 months after injection to study the fate of the injected cells.
  
  
  RESULTS
  Allogeneic injection of the green MSCs is safe; no observable side effects or signs of graft versus host disease were observed. By 4',6-diamidino-2-phenylindole (DAPI) counterstained frozen sections, the green cells were found migrating from the injected area into deeper layers of myocardium over the course of 1 to 6 weeks. By immunofluorescent staining, the green cells were associated with smooth muscle actin or von Willebrand factor positive cells, suggesting that the transplanted cells were contributing to the formation of new vessels. We found no evidence that these cells were associated with the new generation of cardiac myocytes. Three months after injection, clusters of MSCs still can be found in the middle layer of ischemic myocardium; however, no unlimited cell growth was found.
  
  
  CONCLUSIONS
  Allogeneic transplantation of green MSCs can be safely used to elucidate the mechanisms of cell-based therapy. The benefits of this therapy appear mainly due to the angiogenesis, not the regeneration, of cardiac myocytes.
authors.affiliation: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1550, USA. zhouyifu@mail.nih.gov
authors.forename: Yifu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.forename: Zuxi
authors.initials: Z
authors.lastname: Yu
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hoyt
authors.forename: Xuan
authors.initials: X
authors.lastname: Qu
authors.forename: Keith A
authors.initials: KA
authors.lastname: Horvath
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001808:Blood Vessels / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D017202:Myocardial Ischemia / Q000601:surgery*; D017154:Stromal Cells / Q000166:cytology* / Q000637:transplantation*; D013552:Swine