BACKGROUND: Hereditary disordered cardiac muscle could be replaced with intact cardiomyocytes derived from genetically intact bone marrow (BM)-derived stem cells. METHODS AND RESULTS: Cardiomyopathic mice with targeted mutation of delta-sarcoglycan gene underwent intra-BM-BM transplantation (IBM-BMT) from transgenic mice expressing green fluorescence protein. The host BM and the peripheral blood were completely reconstituted by donor-derived hematopoietic cells by IBM-BMT. Treatment with granulocyte-colony stimulating factor (G-CSF) markedly increased donor-derived mesenchymal stem cells (MSC) in the BM and their mobilization into the peripheral blood after IBM-BMT. Treatment with isoproterenol (iso) for 7 days caused myocardial damage and left ventricular (LV) dysfunction in the cardiomyopathic mice. Co-treatment with iso and G-CSF increased donor BM cell recruitment to the heart and temporarily improved LV function in the cardiomyopathic mice with or without IBM-BMT. However, the cardiac muscle was not replaced with donor BM-derived cardiomyocytes in the cardiomyopathic mice with or without IBM-BMT, and this was associated with no improvement of LV function of mice aged 20 weeks. CONCLUSIONS: These results suggest that G-CSF enhances engraftment of donor MSC in the BM and their mobilization into the peripheral circulation after IBM-BMT but MSC recruited to the heart do not differentiate into cardiomyocytes and do not repair the dystrophic heart.
BACKGROUND: Hereditary disordered cardiac muscle could be replaced with intact cardiomyocytes derived from genetically intact bone marrow (BM)-derived stem cells. METHODS AND RESULTS:Cardiomyopathicmice with targeted mutation of delta-sarcoglycan gene underwent intra-BM-BM transplantation (IBM-BMT) from transgenic mice expressing green fluorescence protein. The host BM and the peripheral blood were completely reconstituted by donor-derived hematopoietic cells by IBM-BMT. Treatment with granulocyte-colony stimulating factor (G-CSF) markedly increased donor-derived mesenchymal stem cells (MSC) in the BM and their mobilization into the peripheral blood after IBM-BMT. Treatment with isoproterenol (iso) for 7 days caused myocardial damage and left ventricular (LV) dysfunction in the cardiomyopathicmice. Co-treatment with iso and G-CSF increased donor BM cell recruitment to the heart and temporarily improved LV function in the cardiomyopathicmice with or without IBM-BMT. However, the cardiac muscle was not replaced with donor BM-derived cardiomyocytes in the cardiomyopathicmice with or without IBM-BMT, and this was associated with no improvement of LV function of mice aged 20 weeks. CONCLUSIONS: These results suggest that G-CSF enhances engraftment of donor MSC in the BM and their mobilization into the peripheral circulation after IBM-BMT but MSC recruited to the heart do not differentiate into cardiomyocytes and do not repair the dystrophic heart.
Authors: A Marmotti; F Castoldi; R Rossi; S Marenco; A Risso; M Ruella; A Tron; A Borrè; D Blonna; C Tarella Journal: Knee Surg Sports Traumatol Arthrosc Date: 2012-08-08 Impact factor: 4.342
Authors: C Zhang; X-H Chen; X Zhang; L Gao; L Gao; P-Y Kong; X-G Peng; A-H Sun; Y Gong; D-F Zeng; Q-Y Wang Journal: Transfus Med Date: 2010-02-01 Impact factor: 2.019
Authors: Martin J Elliott; Paolo De Coppi; Simone Speggiorin; Derek Roebuck; Colin R Butler; Edward Samuel; Claire Crowley; Clare McLaren; Anja Fierens; David Vondrys; Lesley Cochrane; Christopher Jephson; Samuel Janes; Nicholas J Beaumont; Tristan Cogan; Augustinus Bader; Alexander M Seifalian; J Justin Hsuan; Mark W Lowdell; Martin A Birchall Journal: Lancet Date: 2012-07-26 Impact factor: 79.321