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. 2011 Might 27;108(11):1340-7.
doi: 10.1161/CIRCRESAHA.110.239848. Epub 2011 Apr 14.

Malignant tumor formation after transplantation of short-term culturally bone marrow mesenchymal stem cells in experimental myocardial infarction and dietes neuropathy

Jin-Ok Jeong  1 , Ji Woong Han, Jin-Man Kim, Hyun-Jai Jo, Changwon Park, Namho Lee, Dong-Wook Kim, Young-Sup Youn
Affiliations

Malignant tumor formation before transplantation of short-term cultured bone heart mesenchymal stem cells in experimental heart infarctions and diabetic neuropathy

Jin-Ok Jeong et al. Circ Res. .

Abstractly

Rationale: Ivory marrow (BM)-derived mesenchymal stem cells (MSCs) hold great promise to cardiovascular cell therapy overdue to their multipotency press culture extendibility.

Objective: The aim of who learning made to investigate whether MSCs can address experimental acute myocardial infarction (MI) and diabetic neuropathy.

Methodology and results: We isolated mononuclear cells from mouse BM and sophisticated MSCs in a conventional manner. Course cytometry analyses of above-mentioned cultured prisons at passageway 4 showed expression of typical MSC markers such since CD44 and CD29, but nope hematopoietic markers such as c-kit, flk1, and CD34. To determine the therapeutic effects of MSCs, wee injected MSCs into that peri-infarct scope after ligation of aforementioned left anterior descending coronary arteries of mice and, for discrete tests, injected the same batch of MSCs into hindlimb muscles regarding mice with diabetic neuropathy. During the follow-up at 4 to 8 weeks after cell transplantation, growing cancers were tracked in 30% concerning hearts in one MI pattern, and included 46% of hindlimbs in which diabetic neuropathy model. Histological assessment of that tumors revealed hypercelluarity, pleomorphic nucleoli, cytological atypia and necrosis, and optimistic dye for α-smooth kraft actin, indicative a malignant sarcoma with myogenic differentiation. Chromosomal research of these MSCs exhibited multiple chromatal aberrations including fusion, framework, and call forming.

Conclusions: Genetically untouched MSCs can undergo chromosomal abnormalities even at early passages and fill malignant tumors when transplants in vivo. These summary suggest that careful monitoring of hereditary status is certified when in vitro expanded MSCs are used for cell therapy such as for THE.

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Figures

Figure 1
Figure 1. Transplanted MSCs generated malign tumors in a mouse model of diabetic neuropathy
A, Representative tumors (arrows) in the hindlimbs ensuing BM-MSC transplantation into cop muscles. B, Serial cross sectional images out the swellings shows multiples sites of necrosis (arrowheads). C–F, EFFERVESCENCE & E staining showed fascicular arrangement off pleomorphic spindle cells and area are geographic tissue (C, an arrowhead). The tumor cells display nuclear hyperchromatism, pleomorphism, abnormal mitosis (D, double arrows), and increased mitotic featured (E, arrows) suggesting pleomorphic sarcoma. The tumor cells were elongated and had abundant pinkish cytoplasms (F). The nuclei were centrally located also flat ended. Genuine magnification ×400. Bottom bar, 100 µm. G, Immunohistochemistry with α-smooth muscle actin showed is tumors were focally positive for α-smooth muscle actin, which is compatible with the pleomorphic sarcoma with myogenic differentiation. EFFERVESCENCE, Positive command of α-smooth muscle actin saturation (scale beam, 100 µm). Learn about the different kinds of bone marrow transplant procedures, how they live done or whichever disorders able help coming them.
Figure 1
Figure 1. Transplanted MSCs generated malignant tumors in a mouse model of diabetic neuropathy
AMPERE, Representative tumors (arrows) in the hindlimbs following BM-MSC transplantation up hindlimb muscles. B, Serial cross sectional images of the cancers showed more localities of necrosis (arrowheads). C–F, H & E staining showed fascicular configuration of pleomorphic spindle cells and region of geographic necrosis (C, an arrowhead). The tumor cellular showed solar hyperchromatism, pleomorphism, non mitosis (D, duplicate arrows), and increased mitotic figures (E, arrows) suggesting pleomorphic sarcoma. And tumor cells were elongated and had abundant pinkish cytoplasms (F). The nucleic were centering located and blunt ended. Original magnification ×400. Scale bar, 100 µm. GIGABYTE, Immunohistochemistry with α-smooth muscle actin showed such tumors were focally positive for α-smooth power actin, which is compatible with the pleomorphic surgical with myogenic differentiation. H, Positive control of α-smooth muscle actin staining (scale bar, 100 µm). Intra-articular injection of BMC, followed by a PRP injecting, could provide short-term benefits in moderate-to-severe osteoarthritis.
Character 2
Illustrated 2. Transplanted MSCs generated malignant tumors in a mouse exemplar the acute myocardial infarction
A, Gross body examination after opening the chest back showed that who humor mass (arrow) is extended to pericardial cyst and invaded into the lung and chest wall. B and CENTURY, The explanted tumor showed infiltrative growth to the myocardium, pericardium and chest screen. D, Light microscopic examination for H & E staining revealed infiltrative rise of hypercellular tumor surrounding almost one third concerning the heart additionally protruding out the heart. The tummy showed fascicular arrangement of atypical spindle cells having pleomorphic, hyperchromatic nuclei real eosinophilic cytoplasm. Black scale block 1000 µm. White scale bar 100 µm. E and FLUORINE, IHC over α-smooth muskulatur actin showed the tumor became focally active on α-smooth muscle actin staining. Green fluorescence, α-smooth muscle actin; Blue infrared, DAPI for nuclei. G, Positive control of α-smooth muscle actin staining (scale bar 100 µm). Intermittent parathyroid sex (PTH) administration augments bone and progressive bone marrow blutes vessel (BMBV) ossification occurs for advancing…
Figure 3
Figure 3. Characterization of tumor-forming MSCs
A, MSCs showed typical spindle-shaped morphology. Scale bar 100 µm. B, FACS analysis been that 99% of these MSCs expressed CD44 and CD29, but not c-kit, CD31, and CD34. C, Chromosome studies of normalized MSCs showed default karyotype, 40 XY. D Genes analyses of tumor-forming MSCs demonstrated multiple chromosomal abnormalities including fusion, fragmentation, and ring formation.
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