Am J Stem Cell 2012;1(1):22-30

Review Article
Specific differentiation of mesenchymal stem cells by small molecules

Heesang Song, Woochul Chang, Byeong-Wook Song, Ki-Chul Hwang

Department of Biochemistry and Molecular Biology,Chosun University School of Medicine, Gwangju 501-759, Republic of Korea;
Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA; Severance Biomedical Science Institute,
Cardiovascular Research Institute and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-
752, Republic of Korea

Received July 20, 2011; accepted August 3, 2011; Epub August 18, 2011; published January 1, 2012

Abstract: Mesenchymal stem cells (MSCs) are multipotent, self-renewing cells harboring multi-lineage differentiation potential and
immunosuppressive properties that make them an attractive candidate for biological cell-based regenerative medicine. In addition to its
undoubted clinical interest, controlling the fate and behaviors of MSCs is a crucial prerequisite for their therapeutic applications in
regenerative medicine. Stem cell differentiation and modulation of functional activities are generally controlled by “cocktails” of growth
factors, signaling molecules, and/or genetic manipulations. However, these approaches have several limiting factors, such as undefined
conditions leading to heterogeneous populations of cells and unexpected risks of virus-mediated genetic modifications. Small
molecules targeting specific signaling pathways have been shown to be key modulators in controlling stem cells’ fate and function.
Small molecules are also important tools for understanding mechanistic and developmental processes. Furthermore, the precise mode
of action of small molecules for controlling MSCs fate is still under study. However, Wnt, GSK, and other protein kinases signaling
pathways are likely to be involved. These target-based manipulations of stem cells fate by small molecules provide new insights into
stem cell biology, and facilitate the development of regenerative medicine using stem cells. Here, we review the recent progress in
controlling MSCs fate and functional activities by small molecules. (AJSC1107001).

Keywords: Mesenchymal stem cells, cell fate, differentiation, small molecules

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Address all correspondence to:
Dr. Ki-Chul Hwang
Severance Biomedical Science Institute
Cardiovascular Research Institute and Brain Korea 21 Project for Medical Science
Yonsei University College of Medicine
Seoul 120-752
Republic of Korea
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