Spherically Symmetric Mesenchymal Stromal Cell Bodies Inherent with Endogenous Extracellular Matrices for Cellular Cardiomyoplasty §

Authors

  • Chung-Chi Wang,

    1. Divisions of Cardiovascular Surgery, Veterans General Hospital, Taichung, Taiwan, Republic of China
    2. College of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
    Search for more papers by this author
  • Chun-Hung Chen,

    1. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China
    Search for more papers by this author
  • Shiaw-Min Hwang,

    1. Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China
    Search for more papers by this author
  • Wei-Wen Lin,

    1. Divisions of Cardiology, Veterans General Hospital, Taichung, Taiwan, Republic of China
    Search for more papers by this author
  • Chih-Hao Huang,

    1. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China
    Search for more papers by this author
  • Wen-Yu Lee,

    1. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China
    Search for more papers by this author
  • Yen Chang,

    Corresponding author
    1. Divisions of Cardiovascular Surgery, Veterans General Hospital, Taichung, Taiwan, Republic of China
    2. College of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China
    • Yen Chang, Division of Cardiovascular Surgery, Veterans General Hospital, Taichung 40705, Taiwan, Republic of China

      Hsing-Wen Sung, Department of Chemical Engineering/Bioengineering Program, National Tsing Hua University, Hsinchu 30013, Taiwan, Republic of China

    Search for more papers by this author
    • Telephone: +886-4-2374-1206; Fax: +886-4-2374-1323

  • Hsing-Wen Sung

    Corresponding author
    1. Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China
    • Yen Chang, Division of Cardiovascular Surgery, Veterans General Hospital, Taichung 40705, Taiwan, Republic of China

      Hsing-Wen Sung, Department of Chemical Engineering/Bioengineering Program, National Tsing Hua University, Hsinchu 30013, Taiwan, Republic of China

    Search for more papers by this author
    • Telephone: +886-3-574-2504; Fax: +886-3-572-6832


  • First published online in STEM CELLSExpress January 8, 2009.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    Author contributions: C.-C.W. and C.-H.C.: collection and assembly of data, data analysis and interpretation, manuscript writing; S.-M.H.: provision of study material, final approval of manuscript; W.-W.L., C.-H.H., and W.-Y.L.: collection and assembly of data, data analysis and interpretation; Y.C. and H.-W.S.: conception and design, manuscript writing, administration support, financial support, final approval of manuscript. C.-C.W. and C.-H.C. contributed equally to this article.

Abstract

Cell transplantation via direct intramyocardial injection is a promising therapy for patients with myocardial infarction; however, retention of the transplanted cells at the injection sites remains a central issue following injection of dissociated cells. Using a thermoresponsive hydrogel system with a multiwell structure, we successfully developed an efficient technique to generate spherically symmetric bodies of mesenchymal stromal cells (MSCs) inherent with endogenous extracellular matrices (ECMs) for direct intramyocardial injection. After injection through a needle and upon transferring to another growth surface, the time required to attach, migrate, and proliferate was significantly shorter for the MSC bodies than the dissociated MSCs. Employing a syngeneic rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n = 10): sham, phosphate-buffered saline, dissociated MSCs, and MSC bodies. The results obtained in the echocardiography and catheterization measurements demonstrated that the MSC body group had a superior heart function to the dissociated MSC group. Histologically, it was found that MSC bodies could provide an adequate physical size to entrap into the interstices of muscular tissues and offer a favorable ECM environment to retain the transplanted cells intramuscularly. Additionally, transplantation of MSC bodies stimulated a significant increase in vascular density, thus improving the cardiac function. These results indicated that the spherically symmetric bodies of MSCs developed in the study may serve as a cell-delivery vehicle and improve the efficacy of therapeutic cell transplantation. STEM CELLS 2009;27:724–732

Ancillary