title: Regulatory T cells enhance mesenchymal stem cell survival and proliferation following autologous cotransplantation in ischemic myocardium.
abstract: OBJECTIVE
  We sought to investigate if autologous freshly isolated regulatory T cells (Tregs) provide a protective and supportive role when cotransplanted with mesenchymal stem cells (MSCs).
  
  
  METHODS
  In a porcine model of chronic ischemia, autologous MSCs were isolated and expanded ex vivo for 4 weeks. Autologous Treg cells were freshly isolated from 100 mL peripheral blood and purified by fluorescence-activated cell sorting. MSCs and Treg cells were then cotransplanted into the chronic ischemic myocardium of Yorkshire pigs by direct intramyocardial injection (1.2 × 10(8) MSCs plus an average of 1.5 million Treg cells in 25 injection sites). Animals were killed 6 weeks postinjection to study the fate of the cells and compare the effect of combined MSCs + Treg cells transplantation versus MSCs alone.
  
  
  RESULTS
  The coinjection of MSCs along with Tregs was safe and no deleterious side effects were observed. Six weeks after injection of the cell combination, spherical MSCs clusters with thin layer capsules were found in the injected areas. In animals treated with MSCs only, the MSC clusters were less organized and not encapsulated. Immunofluorescent staining showed CD25+ cells among the CD90+ (MSC marker) cells, suggesting that the injected Treg cells remained present locally, and survived. Factor VIII+ cells were also prevalent suggesting new angiogenesis. We found no evidence that coinjections were associated with the generation of cardiac myocytes.
  
  
  CONCLUSIONS
  The cotransplantation of Treg cells with MSCs dramatically increased the MSC survival rate, proliferation, and augmented their role in angiogenesis, which suggests a new way for future clinical application of cell-based therapy.
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. Electronic address: zhouyifu@mail.nih.gov.
authors: Yifu
authors: Y
authors: Zhou
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Avneesh K
authors: AK
authors: Singh
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Robert F
authors: RF
authors: Hoyt
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Suna
authors: S
authors: Wang
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Zuxi
authors: Z
authors: Yu
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Timothy
authors: T
authors: Hunt
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Bogdan
authors: B
authors: Kindzelski
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Philip C
authors: PC
authors: Corcoran
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Muhammad M
authors: MM
authors: Mohiuddin
authors: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
authors: Keith A
authors: KA
authors: Horvath
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism; D017202:Myocardial Ischemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018919:Neovascularization, Physiologic; D034421:Sus scrofa; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D013997:Time Factors; D014182:Transplantation, Autologous