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Bioengineering Technique Progress of Direct Cardiac Reprogramming

A New Perspective from Microbubbles and UTMD

  • Living reference work entry
  • First Online:
Handbook of Stem Cell Therapy

  • 60 Accesses

Abstract

The combination of heart-specific transcription factors GATA4, MEF2C, and TBX5 (GMT) has been proven to have the ability to directly reprogram cardiac fibroblasts; this approach is considered a promising regenerative technique. Meanwhile, research on microbubbles as biological vectors has made great progress in recent years. This study describes the loading of GMT lentiviral vectors on cationic microbubbles and the release of these direct-reprogramming vectors into an infarcted myocardium by ultrasound targeted microbubble destruction (UTMD) to repair the cardiac tissue. Lentivirus which encode GATA4, MEF2C, and TBX5 transcription factors were generated via a lentiviral production system and were confirmed to have a direct reprogramming ability in vitro. Combined with the cationic microbubbles, UTMD-mediated gene delivery was evaluated, and the gene transfection efficiency was optimized in an in vitro experiment on rat cardiac fibroblasts. With UTMD-mediated direct reprogramming, the viral vector particles were directly deposited in cardiac tissue and repaired the infarcted myocardium. An immunofluorescence assay and histological examination confirmed newborn cardiomyocytes and neo-angiogenesis after a 4-week follow-up of the treated rats. All treated groups showed ventricular-function improvement according to cardiac magnetic resonance imaging and echocardiography. This chapter reports a novel strategy for the delivery of direct-reprogramming lentiviral vectors to a target acute myocardial infarction zone by using UTMD as a tissue repair therapy.

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Abbreviations

CFs:

Cardiac fibroblasts

cTnI:

Cardiac troponin-I

cTnT:

Cardiac troponin-I

GMT:

Gata4, MEF2c, and TBX5

H&E:

Hematoxylin and Eosin

HDAC:

Histone deacetylase

HIV:

Human immunodeficiency virus

iCMs:

Induced cardiomyocyte-like cells

IHD:

Ischemic heart disease

iPSCs:

Induced pluripotent stem cells

LAD:

Left anterior descending

LV:

Left ventricle

LVEF:

LV-ejection fraction

MCAs:

Microbubble ultrasound contrast agents

MI:

Myocardial infarction

UTMD:

Ultrasound-targeted microbubble destruction

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Authors and Affiliations

  1. Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Dingqian Liu & Changfa Guo

  2. Department of Basic Sciences, Sulaiman AlRajhi Medical School, Al Bukairiyah, Kingdom of Saudi Arabia

    Khawaja Husnain Haider

Authors
  1. Dingqian Liu
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  2. Khawaja Husnain Haider
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  3. Changfa Guo
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Corresponding author

Correspondence to Changfa Guo .

Editor information

Editors and Affiliations

  1. Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukairiyah, Saudi Arabia

    Khawaja H. Haider

Section Editor information

  1. Department of Basic Sciences, Sulaiman AlRajhi University, Al Bukairiyah, Saudi Arabia

    Khawaja H. Haider

  2. University of Modena and Reggio Emilia, Modena, Italy

    Beatrice Aramini

  3. Interamerican Open University, Buenos Aires, Argentina

    Elio A. Prieto Gonzalez

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Liu, D., Haider, K.H., Guo, C. (2022). Bioengineering Technique Progress of Direct Cardiac Reprogramming. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_27-1

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  • DOI: https://doi.org/10.1007/978-981-16-6016-0_27-1

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