A strategy to optimize mesenchymal stem cell function pertinent to bone tissue engineering

Date
2011
Authors
Creecy, Courtney Michelle
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Abstract

The present research study is motivated by intriguing, but limited, information reported in the literature of phenomenological studies showing enhanced bone-fracture healing in animals under electric stimulation. However, the underlying mechanisms at the cellular- and molecular-levels are not fully understood. The present in vitro research aims to overcome such limitations by establishing the presently undefined conditions that expedite the process of adult human mesenchymal stem cell (MSC) differentiation into osteoblasts.

For this purpose, a multidisciplinary approach, which encompassed aspects of cellular engineering, molecular biology, biochemistry, and tissue engineering, was implemented. Specifically, molecular and biochemical assays were used to determine the effects of alternating electric current on MSCs cultured in three-dimensional constructs; these effects were further validated through comparisons of the effects of alternating electric current on MSC differentiation to those of a well-established biochemical stimulus, bone morphogenetic proteins.

The present research study is the first to provide evidence that alternating electric current accelerated and enhanced the differentiation of adult human mesenchymal stem cells toward the osteoblastic pathway. Specifically, exposure of mesenchymal stem cells to either 10 or 40 µA alternating electric current for six hours per day, for various periods of time up to 14 days, enhanced gene expression of select proteins pertinent to the osteogenic differentiation pathway. Most importantly, gene expression of proteins pertinent to either the adipogenic or chondrogenic pathways was not detected when MSCs were exposed to the aforementioned alternating electric current conditions tested in the present study. These in vitro results elucidated aspects of the molecular-level mechanisms through which this stem cell differentiation may occur in vivo under alternating electric current.

In addition to providing fundamental information pertinent to bone physiology, the results of the present study provided evidence that alternating current, a biophysical stimulus, alone has the yet untapped potential to achieve successful tissue engineering alternatives to traditional bone grafts; such novel methodologies are needed to meet the projected clinical demands for bone tissue repair and healing applications. In this respect, the present study could have major impact on the bioengineering, biotechnology, and clinical milieu.

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Keywords
alternating electric current, bone morphogenetic proteins, collagen hydrogels, mesenchymal stem cells, osteoblasts, osteogenic differentiation
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Department
Biomedical Engineering