. e5 `3 D, G1 N. m2 U6 O: fFrom the Division of Cardiovascular Research, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA (J.-O.J., H.-J.C., N.L., Y.-S.Y.); Department of Internal Medicine (J.-O.J.) and Department of Pathology (J.K.), College of Medicine, Chungnam National University, Daejeon, Korea; Department of Internal Medicine, Seoul National University Hospital, Chongno-Gu, Yongon-Dong, Seoul, Korea (H.-J.C.); Division of Cardiology, Kangnam Sacred Heart Hospital, Hallym University School of Medicine, Seoul, Korea (N.L.); Department of Pharmacology, University of Illinois at Chicago, Chicago, IL (C.P.); Stem Cell Research Center, 21C R&D Program of Ministry of Education, Science, and Technology, Yonsei University Medical Center, Seoul, Korea (D.-W.K.); and Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA (J.W.H., C.P., Y.-S.Y.). 1 C6 X7 \% J" z
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Correspondence to Young-Sup Yoon, MD, PhD, Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, WMB 3009, Atlanta, GA 30322. E-mail yyoon5@emory.edu C& i! Y4 Q3 y: X1 H ' r) a' J. N j% zAbstract : V. s& j& B( K3 k" n" C0 k* k5 A! q6 j9 F# J! N3 Y+ B
Rationale:Bone marrow (BM)–derived mesenchymal stem cells (MSCs) hold great promise for cardiovascular cell therapy owing to their multipotency and culture expandability. # R+ ]9 \: I0 N0 V ; {* J# s! Z6 Y+ |, @6 XObjective:The aim of the study was to investigate whether MSCs can treat experimental acute myocardial infarction (MI) and diabetic neuropathy. ) S3 X/ m4 A5 p! Q" T
' J8 a% Z) @0 c" JMethods and Results:We isolated mononuclear cells from mouse BM and cultured MSCs in a conventional manner. Flow cytometry analyses of these cultured cells at passage 4 showed expression of typical MSC markers such as CD44 and CD29, but not hematopoietic markers such as c-kit, flk1, and CD34. To determine the therapeutic effects of MSCs, we injected MSCs into the peri-infarct area after ligation of the left anterior descending coronary arteries of mice and, as separate experiments, injected the same batch of MSCs into hindlimb muscles of mice with diabetic neuropathy. During the follow-up at 4 to 8 weeks after cell transplantation, growing tumors were observed in 30% of hearts in the MI model, and in 46% of hindlimbs in the diabetic neuropathy model. Histological examination of the tumors revealed hypercelluarity, pleomorphic nucleoli, cytological atypia and necrosis, and positive staining for α-smooth muscle actin, indicative of malignant sarcoma with myogenic differentiation. Chromosomal analysis of these MSCs showed multiple chromosomal aberrations including fusion, fragmentation, and ring formation. 3 e) @- ?' a$ g# K1 }: [! x5 q9 o9 u, R _
Conclusions:Genetically unmodified MSCs can undergo chromosomal abnormalities even at early passages and form malignant tumors when transplanted in vivo. These results suggest that careful monitoring of chromosomal status is warranted when in vitro expanded MSCs are used for cell therapy such as for MI. 3 R. `8 I; u8 q4 s- v: O 结论：未经基因修饰的干细胞在早期传代过程中可发生染色体异常，并且移植后会在体内形成恶性肿瘤。这些结果表明，体外扩增间充质干细胞用于心肌梗死治疗等疾病的细胞治疗时必须严格考察染色体的状态。# }( f. e2 t8 A: C* n. N ]5 D
Key Words: bone marrow • mesenchymal stem cells • malignant tumors • transplantation • ischemia) E6 s1 Q) X$ n& ?$ o http://circres.ahajournals.org/c ... RESAHA.110.239848v12 Z2 V% I) t0 {6 X, r
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5楼原文 感谢longer 提供作者: nightvsday 时间: 2011-5-3 20:30