Fibroblast sheets co-cultured with endothelial progenitor cells improve cardiac function of infarcted hearts

Kobayashi, Hiroshi; Shimizu, Tatsuya; Yamato, Masayuki; Tono, Kayoko; Masuda, Haruchika; Asahara, Takayuki; Kasanuki, Hiroshi; Okano, Teruo

doi:10.1007/s10047-008-0421-8

Cited by 78 publications

(46 citation statements)

References 39 publications

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“…Thus far, one major limitation has been insufficient vascularization of engineered tissues, which is essential for the supply of oxygen, nutrients, and immune cells as well as the removal of cellular by-products and waste. This is particularly important in cardiac tissue engineering approaches, where recent studies have demonstrated the feasibility of engineering functional cardiac muscle in vitro, with promising results after graft implantation in animal models (26,29,37,41,53). These studies indicate that revascularization of an engineered graft is critical for successful graft implantation and regeneration of ischemic cardiac tissue.…”

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confidence: 96%

Complex temporal regulation of capillary morphogenesis by fibroblasts

Hurley

Balaji

Narmoneva

2010

American Journal of Physiology-Cell Physiology

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Interactions between endothelial and stromal cells are important for vascularization of regenerating tissue. Fibroblasts (FBs) are responsible for expression of angiogenic growth factors and matrix metalloproteinases, as well as collagen deposition and fibrotic myocardial remodeling. Recently, self-assembling peptide nanofibers were described as a promising environment for cardiac regeneration due to its synthetic nature and control over physiochemical properties. In this study, peptide nanofibers were used as a model system to quantify the dual role of fibroblasts in mediating angiogenesis chemically via expression of angiogenic factors and mechanically via cell-mediated scaffold disruption, extracellular matrix deposition, and remodeling. Human microvascular endothelial cells (ECs), FBs, or cocultures were cultured in three-dimensional nanofibers for up to 6 days. The peptide nanofiber microenvironment supported cell migration, capillary network formation, and cell survival in the absence of detectable scaffold contraction and proteolytic degradation. FBs enhanced early capillary network formation by "assisting" EC migration and increasing vascular endothelial growth factor and Angiopoietin-1 expression in a temporal manner. EC-FB interactions attenuated FB matrix metalloproteinase-2 expression while increasing collagen I deposition, resulting in greater construct stiffness and a more stable microenvironment in cocultures. Whereas FBs are critical for initial steps of angiogenesis in the absence of external angiogenic stimulation, coordinated efforts by ECs and FBs are required for a balance between cell-mediated scaffold disruption, extracellular matrix deposition, and remodeling at later time points. The findings of this study also emphasize the importance of developing a microenvironment that supports cell-cell interactions and cell migration, thus contributing toward an optimal environment for successful cardiac regeneration strategies.

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confidence: 96%

Complex temporal regulation of capillary morphogenesis by fibroblasts

Hurley

Balaji

Narmoneva

2010

American Journal of Physiology-Cell Physiology

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“…22 Another report showed that a dermal fibroblast sheet co-cultured with endothelial progenitor cells was more effective than either single cell-type sheet for improving damaged heart function, accompanied by the inhibition of fibrotic tissue formation and the acceleration of neovascularization in the infarcted myocardium. 23 Thus, the paracrine effect may be improved by combining different cell sources; however, further investigation focused on determining the optimal combinations of cell sources is needed.…”

Section: Fig 8 Characterization Of Transplanted Cells (A)mentioning

confidence: 99%

Addition of Mesenchymal Stem Cells Enhances the Therapeutic Effects of Skeletal Myoblast Cell-Sheet Transplantation in a Rat Ischemic Cardiomyopathy Model

Shudo

Miyagawa

Ohkura

et al. 2014

Tissue Engineering Part A

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Introduction: Functional skeletal myoblasts (SMBs) are transplanted into the heart effectively and safely as cell sheets, which induce functional recovery in myocardial infarction (MI) patients without lethal arrhythmia. However, their therapeutic effect is limited by ischemia. Mesenchymal stem cells (MSCs) have prosurvival/ proliferation and antiapoptotic effects on co-cultured cells in vitro. We hypothesized that adding MSCs to the SMB cell sheets might enhance SMB survival post-transplantation and improve their therapeutic effects. Methods and Results: Cell sheets of primary SMBs of male Lewis rats (r-SMBs), primary MSCs of human female fat tissues (h-MSCs), and their co-cultures were generated using temperature-responsive dishes. The levels of candidate paracrine factors, rat hepatocyte growth factor and vascular endothelial growth factor, in vitro were significantly greater in the h-MSC/r-SMB co-cultures than in those containing r-SMBs only, by real-time PCR and enzyme-linked immunosorbent assay (ELISA). MI was generated by left-coronary artery occlusion in female athymic nude rats. Two weeks later, co-cultured r-SMB or h-MSC cell sheets were implanted or no treatment was performed (n = 10 each). Eight weeks later, systolic and diastolic function parameters were improved in all three treatment groups compared to no treatment, with the greatest improvement in the co-cultured cell sheet transplantation group. Consistent results were found for capillary density, collagen accumulation, myocyte hypertrophy, Akt-signaling, STAT3 signaling, and survival of transplanted cells of rat origin, and were related to poly (ADP-ribose) polymerase-dependent signal transduction. Conclusions: Adding MSCs to SMB cell sheets enhanced the sheets' angiogenesis-related paracrine mechanics and, consequently, functional recovery in a rat MI model, suggesting a possible strategy for clinical applications.

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“…Whereas the transplantation of HGF overexpressed skeletal myoblast sheets induced effectively a stimulated angiogenesis in the infarcted and non-infarcted areas, cardiac function was hardly enhanced by HGF [76]. Kobayashi et al 138 Cell Therapy for Cardiovascular Disease showed that the transplantation of EPC cocultured fibroblast sheets improved heart function more significantly than only fibroblast sheet implantation or EPC injection [77]. On the basis of these favorable results in various animal models, a clinical trial using autologous skeletal myoblast sheets is now in progress.…”

Section: Three-dimensional Tissues Fabricated By Using Autologous Celmentioning

confidence: 99%