Original Article
Implantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart

https://doi.org/10.1016/S0022-2828(03)00211-6Get rights and content

Abstract

Myocardial infarction may cause sudden cardiac death and heart failure. Adult cardiac myocytes do not replicate due to lack of a substantive pool of precursor, stem, or reserve cells in an adult heart. Ventricular myocytes following myocardial infarction are replaced by fibrous tissue and this leads to congestive heart failure in severe cases. Anversa et al. described that resident cardiac stem cells are present in the heart, and can repair the damaged mycardium by myocyte regeneration. Recent findings suggest the feasibility of cardiac repair using cell transplantation. However, it remains controversial which cell types are the best for cell transplantation in the ischemic heart. In this study, we demonstrate that cultured bone marrow stromal cells (MSCs) and Lin bone marrow cells upon transplantation differentiate into myocytes and endothelial cells in the ischemic heart, eventually reducing both infarct size and fibrosis.

Introduction

Several cell types have been transplanted into the heart, including fetal cardiomyocytes [3], [4], autologous [5], [6], [7] or syngeneic [8] skeletal myoblasts, smooth muscle cells [9], immortalized myoblasts [10], fibroblasts [11], embryonic stem cells [12], [13], and bone marrow-derived stem cells [14], [15], [16], [17]. Bone marrow-derived stem cells are capable of functional plasticity. After bone marrow transplantation, donor-derived stem cells have been found in diverse non-hematopoietic tissues, such as skeletal muscle [18], cardiac muscle [14], [16], [17], [19], smooth muscle cells [20], vascular endothelium [14], [16], [17], [21], [22], and liver bile ducts [23], [24]. Recent experimental evidence suggests that they are capable of myocardial repair and induce angiogenesis in the ischemic heart [14], [15], [16], [17].

Section snippets

Isolation and culture of bone marrow stromal cells (MSCs)

Bone marrow cells were extracted from the tibias and femurs of CL57/6 12-week-old mice and were suspended in Iscove’s-modified Dulbecco’s medium (IMDM, GibcoBRL, Gaithersburg, MD, USA) with 2% heat-inactivated fetal calf serum (FCS, GibcoBRL), penicillin G (100 U/ml), and streptomycin (100 μg/ml). After the cells were counted in a hemocytometer, 2–5 × 107 cells were inoculated into 100–mm culture dishes. After culturing cells for 2 d in complete medium, IMDM with 20% FCS, penicillin G

Characterization of bone marrow stromal cells

Bone marrow cells are collected from the tibias and femurs of mice and are plated into a culture dish. Two days after plating, MSCs consisted of heterogeneous cell types as spindle-shaped, round, and a few of polygonal types. Mesenchymal cells are almost spindle shapes and attached to the culture dish, and hematopoietic cells were round and did not attach to the dish. The culture medium was changed every 3 d to wash away the floating hematopoietic cells. Two weeks later, MSCs were relatively

Discussion

In this study, we used two types of bone marrow cells: fresh and directly extracted Lin cells and cultured MSCs and evaluated the effect of their engraftment on infarct size and amount of fibrosis in the ischemic heart. We observed that engrafted bone marrow cells had differentiated into cardiomyocytes and vascular cells and reduced infarct size and fibrosis. Currently MSCs [14], [15], hematopoietic stem cells [16], [17], and bone marrow-derived endothelial progenitor cells have been used for

Uncited references

The following references have been cited in the Abstract, and not in the main text of the article: [1], [2].

References (33)

  • D.A Taylor et al.

    Regenerating functional myocardium: improved performance after skeletal myoblast transplantation

    Nat M

    (1998)
  • D Marelli et al.

    Cell transplantation for myocardial repair: an experimental approach

    Cell Transplant

    (1992)
  • P.D Kessler et al.

    Myoblast cell grafting into heart muscle: cellular biology and potential applications

    Annu Rev Physiol

    (1999)
  • C.E Murry et al.

    Skeletal myoblast transplantation for repair of myocardial necrosis

    J Clin Invest

    (1996)
  • K.A Hutcheson et al.

    Comparison of benefits on myocardial performance of cellular cardiomyoplasty with skeletal myoblasts and fibroblasts

    Cell Transplant

    (2000)
  • M.G Klug et al.

    Genetically selected cardiomyocytes from differentiating embronic stem cells form stable intracardiac grafts

    J Clin Invest

    (1996)
  • Cited by (0)

    The review process for this manuscript was handled by consulting editor, Stephen F. Vatner, MD.

    View full text