title: Thymosin β4 increases the potency of transplanted mesenchymal stem cells for myocardial repair.
abstract: BACKGROUND
  Thymosin β4 (Tβ4) has been shown to enhance the survival of cultured cardiomyocytes. Here, we investigated whether the cytoprotective effects of Tβ4 can increase the effectiveness of transplanted swine mesenchymal stem cells (sMSCs) for cardiac repair in a rat model of myocardial infarction (MI).
  
  
  RESULTS
  Under hypoxic conditions, cellular damage (lactate dehydrogenase leakage), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelingc cells), and caspase-8 activity were significantly lower, whereas B-cell lymphoma-extra large protein expression was significantly higher, in sMSCs cultured with Tβ4 (1 μg/mL) than in sMSCs cultured without Tβ4, and Tβ4 also increased sMSC proliferation. For in vivo experiments, animals were treated with basal medium (MI: n=6), a fibrin patch (Patch: n=6), a patch containing sMSCs (sMSC: n=9), or a patch containing sMSCs and Tβ4 (sMSC/Tβ4: n=11); Tβ4 was encapsulated in gelatin microspheres to extend Tβ4 delivery. Four weeks after treatment, echocardiographic assessments of left-ventricular ejection fraction and fractional shortening were significantly better (P<0.05) in sMSC/Tβ4 animals (left-ventricular ejection fraction=51.7 ± 1.1%; fractional shortening=26.7 ± 0.7%) than in animals from MI (39 ± 3%; 19.5 ± 1.7%) and Patch (43 ± 1.4%; 21.6 ± 0.9%) groups. Histological assessment of infarct wall thickness was significantly higher (P<0.05) in sMSC/Tβ4 animals (50%, [45%, 80%]) than in animals from MI (25%, [20%, 25%]) group. Measurements in sMSC (left-ventricular ejection fraction=45 ± 2.6%; fractional shortening=22.9 ± 1.6%; TH = 43% [25%, 45%]), Patch, and MI animals were similar. Tβ4 administration also significantly increased vascular growth, the retention/survival of the transplanted sMSCs, and the recruitment of endogenous c-Kit(+) progenitor cells to the infarcted region.
  
  
  CONCLUSIONS
  Extended-release Tβ4 administration improves the retention, survival, and regenerative potency of transplanted sMSCs after myocardial injury.
authors.affiliation: Division of Cardiology, Department of Medicine (L.Y., P.Z., S.D., L.S., Q.X., J.Z.), Stem Cell Institute (L.Y., J.Z.), and Department of Biomedical Engineering (J.Z.), University of Minnesota, Minneapolis, MN.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Zhang
authors.forename: Sue
authors.initials: S
authors.lastname: Duval
authors.forename: Liping
authors.initials: L
authors.lastname: Su
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiong
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008840:Microfilament Proteins / Q000502:physiology* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D013552:Swine; D013947:Thymosin / Q000502:physiology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000502:physiology*; D000099201:Thymosin beta(4)
chemical_list: D008840:Microfilament Proteins; D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: angiogenesis; microsphere; myocardial infarction; stem cell; tissue engineering
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