Open AccessRole of interleukin‐7 in fusion of rat bone marrow mesenchymal stem cells with cardiomyocytes in vitro and improvement of cardiac function in vivo
Author(s) -
Haneef Kanwal,
Ali Anwar,
Khan Irfan,
Naeem Nadia,
Jamall Siddiqua,
Salim Asmat
Publication year - 2018
Publication title -
cardiovascular therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 46
eISSN - 1755-5922
pISSN - 1755-5914
DOI - 10.1111/1755-5922.12479
Subject(s) - medicine , mesenchymal stem cell , cardiac function curve , transfection , bone marrow , in vivo , stem cell , flow cytometry , andrology , pathology , immunology , microbiology and biotechnology , cell culture , biology , heart failure , genetics
Summary Aims Mesenchymal stem cells ( MSC s) hold significant promise as potential therapeutic candidates following cardiac injury. However, to ensure survival of transplanted cells in ischemic environment, it is beneficial to precondition them with growth factors that play important role in cell survival and proliferation. Aim of this study is to use interleukin‐7 ( IL ‐7), a cell survival growth factor, to enhance the potential of rat bone marrow MSC s in terms of cell fusion in vitro and cardiac function in vivo. Methods Mesenchymal stem cells were transfected with IL ‐7 gene through retroviral vector. Normal and transfected MSC s were co‐cultured with neonatal cardiomyocytes ( CM s) and cell fusion was analyzed by flow cytometry and fluorescence microscopy. These MSC s were also transplanted in rat model of myocardial infarction ( MI ) and changes at tissue level and cardiac function were assessed by histological analysis and echocardiography, respectively. Results Co‐culture of IL ‐7 transfected MSC s and CM s showed significantly higher ( P < 0.01) number of fused cells as compared to normal MSC s. Histological analysis of hearts transplanted with IL ‐7 transfected MSC s showed significant reduction ( P < 0.001) in infarct size and better preservation ( P < 0.001) of left ventricular wall thickness as compared to normal MSC s. Presence of cardiac‐specific proteins, α‐actinin, and troponin‐T showed that the transplanted MSC s were differentiated into cardiomyocytes. Echocardiographic recordings of the experimental group transplanted with transfected MSC s showed significant increase in the ejection fraction and fractional shortening ( P < 0.01), and decrease in diastolic and systolic left ventricular internal diameters ( P < 0.001) and end systolic and diastolic volumes ( P < 0.01 and P < 0.001, respectively). Conclusion Interleukin‐7 is able to enhance the fusogenic properties of MSC s and improve cardiac function. This improvement may be attributed to the supportive action of IL ‐7 on cell proliferation and cell survival contributing to the regeneration of damaged myocardium.