Original ArticleImplantation of bone marrow stem cells reduces the infarction and fibrosis in ischemic mouse heart☆
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].
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The review process for this manuscript was handled by consulting editor, Stephen F. Vatner, MD.