Zhen Ma

Publications (11) View all

• Source

  Available from: Bruce Gao

  Article: Mesenchymal Stem Cell-Cardiomyocyte Interactions under Defined Contact Modes on Laser-Patterned Biochips.

  Zhen Ma, Huaxiao Yang, Honghai Liu, Meifeng Xu, Raymond B Runyan, Carol A Eisenberg, Roger R Markwald, Thomas K Borg, Bruce Z Gao
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  ABSTRACT: Understanding how stem cells interact with cardiomyocytes is crucial for cell-based therapies to restore the cardiomyocyte loss that occurs during myocardial infarction and other cardiac diseases. It has been thought that functional myocardial repair and regeneration could be regulated by stem cell-cardiomyocyte contact. However, because various contact modes (junction formation, cell fusion, partial cell fusion, and tunneling nanotube formation) occur randomly in a conventional coculture system, the particular regulation corresponding to a specific contact mode could not be analyzed. In this study, we used laser-patterned biochips to define cell-cell contact modes for systematic study of contact-mediated cellular interactions at the single-cell level. The results showed that the biochip design allows defined stem cell-cardiomyocyte contact-mode formation, which can be used to determine specific cellular interactions, including electrical coupling, mechanical coupling, and mitochondria transfer. The biochips will help us gain knowledge of contact-mediated interactions between stem cells and cardiomyocytes, which are fundamental for formulating a strategy to achieve stem cell-based cardiac tissue regeneration.
  PLoS ONE 01/2013; 8(2):e56554. · 4.09 Impact Factor
• Source

  Available from: Bruce Gao

  Article: Myosin Filament Assembly onto Myofibrils in Live Neonatal Cardiomyocytes Observed by TPEF-SHG Microscopy.

  Honghai Liu, Yonghong Shao, Wan Qin, Raymond B Runyan, Meifeng Xu, Zhen Ma, Thomas K Borg, Roger Markwald, Bruce Z Gao
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  ABSTRACT: AIMS: Understanding myofibrillogenesis is essential for elucidating heart muscle formation, development, and remodeling in response to physiological stimulation. Here, we report the dynamic assembly process of contractile myosin filaments onto myofibrils in a live cardiomyocyte culture during myofibrillogenesis.Methods and ResultsUtilizing a custom built, two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) imaging system equipped with an onstage incubator, we observed new sarcomere additions in rat neonatal cardiomyocytes during 10 hours of on-stage incubation. The new sarcomere additions occurred at the side of an existing myofibrils, where we observed mature myofibrils acting as templates, or at the interstice of several separated myofibrils. CONCLUSIONS: During sarcomeric addition, myosin filaments are assembled onto the premyofibril laterally. This lateral addition, which proceeds stepwise along the axial direction, plays an important role in the accumulation of Z-bodies to form mature Z-disks and in the regulation of sarcomeric alignment during maturation.
  Cardiovascular research 10/2012; · 5.80 Impact Factor
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  Available from: Zhen Ma

  Article: Cardiogenic Regulation of Stem-Cell Electrical Properties in a Laser-Patterned Biochip.

  Zhen Ma, Qiuying Liu, Honghai Liu, Huaxiao Yang, Julie X Yun, Meifeng Xu, Carol A Eisenberg, Thomas K Borg, Roger Markwald, Bruce Z Gao
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  ABSTRACT: Normal cardiomyocytes are highly dependent on the functional expression of ion channels to form action potentials and electrical coupling with other cells. To fully determine the scientific and therapeutic potential of stem cells for cardiovascular-disease treatment, it is necessary to assess comprehensively the regulation of stem-cell electrical properties during stem cell-cardiomyocyte interaction. It has been reported in the literature that contact with native cardiomyocytes induced and regulated stem-cell cardiogenic differentiation. However, in conventional cell-culture models, the importance of cell-cell contact for stem-cell functional coupling with cardiomyocytes has not been elucidated due to insufficient control of the cell-contact mode of individual cells. Using microfabrication and laser-guided cell micropatterning techniques, we created two biochips with contact-promotive and -preventive microenvironments to systematically study the effect of contact on cardiogenic regulation of stem-cell electrical properties. In contact-promotive biochips, connexin 43 expression was upregulated and relocated to the junction area between one stem cell and one cardiomyocyte. Only stem cells in contact with cardiomyocytes were induced by adjacent cardiomyocytes to acquire electrophysiological properties for action-potential formation similar to that of a cardiomyocyte.
  Cellular and Molecular Bioengineering 09/2012; 5(3):327-336. · 1.95 Impact Factor
• Source

  Available from: Bruce Gao

  Article: Quantitatively analyzing the protective effect of mesenchymal stem cells on cardiomyocytes in single-cell biochips.

  Zhen Ma, Bruce Z Gao
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  ABSTRACT: To understand how stem cells benefit native cardiomyocytes is crucial for cell-based therapies to rescue cardiomyocytes (CMCs) damaged during heart infarction and other cardiac diseases. However, the current conclusions on the protective effect of mesenchymal stem cells (MSCs) were obtained by analyzing the overall amount of protein and factor secretion in a conventional co-culture system. These results neglected the heterogeneity of MSC population and failed to determine the importance of cellular contact to the protective effects. To address these issues, we have constructed two biochips by microfabrication methods and laser-guided cell micropatterning technique. Using the biochips, the protective effect of MSCs on CMCs can be quantitatively analyzed at single-cell level with defined cellular contact. The role of cellular contact on protective effect can be clarified according to our statistical results.
  Biotechnology Letters 03/2012; 34(7):1385-91. · 1.68 Impact Factor
• Article: Laser-patterned stem-cell bridges in a cardiac muscle model for on-chip electrical conductivity analyses.

  Zhen Ma, Qiuying Liu, Honghai Liu, Huaxiao Yang, Julie X Yun, Carol Eisenberg, Thomas K Borg, Meifeng Xu, Bruce Z Gao
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  ABSTRACT: Following myocardial infarction there is an irreversible loss of cardiomyocytes that results in the alteration of electrical propagation in the heart. Restoration of functional electrical properties of the damaged heart muscle is essential to recover from the infarction. While there are a few reports that demonstrate that fibroblasts can form junctions that transmit electrical signals, a potential alternative using the injection of stem cells has emerged as a promising cellular therapy; however, stem-cell electrical conductivity within the cardiac muscle fiber is unknown. In this study, an in vitro cardiac muscle model was established on an MEA-based biochip with multiple cardiomyocytes that mimic cardiac tissue structure. Using a laser beam, stem cells were inserted adjacent to each muscle fiber (cell bridge model) and allowed to form cell-cell contact as determined by the formation of gap junctions. The electrical conductivity of stem cells was assessed and compared with the electrical conductivities of cardiomyocytes and fibroblasts. Results showed that stem cell-myocyte contacts exhibited higher and more stable conduction velocities than myocyte-fibroblast contacts, which indicated that stem cells have higher electrical compatibility with native cardiac muscle fibers than cardiac fibroblasts.
  Lab on a Chip 12/2011; 12(3):566-73. · 5.67 Impact Factor