Forced Expression of Transcription Factors in Human Mesenchymal Cells to Promote Proliferation and Osteogenic Differentiation

Mesenchymal stromal cells (MSCs) derived from human bone marrow have capability to differentiate into cells of mesenchymal lineage (7). Especially, the differentiation capability towards osteogenic cells is very well known. We have already used the patient's MSCs for the treatments of osteoarthritis (8), bone necrosis (2) and bone tumor cases (5). In most cases, the MSCs were culture- expanded from patient's fresh bone marrow cells, and then combined with porous ceramics. The MSCs/ceramics composites were further cultured in a medium containing dexamethasone to promote osteogenic differentiation of the MSCs. In this culture condition, we could detect bone forming osteoblasts together with mineralized bone matrix on the ceramics (7); therefore, we could fabricate cultured bone using patient's bone marrow and ceramics. However, the proliferation and differentiation capability of the MSCs are variable and many lose their capabilities after several passages. With the aim of conferring higher capability on human bone marrow MSCs, some of transcription factors could be introduced into the MSCs. This review paper demonstrates the importance of the transcription factors to promote the osteogenesis as well as proliferation capabilities of human MSCs.

[1]  Katsuhisa Horimoto,et al.  Induction of Pluripotent Stem Cells from Human Third Molar Mesenchymal Stromal Cells*♦ , 2010, The Journal of Biological Chemistry.

[2]  H. Ohgushi,et al.  Forced expression of Sox2 or Nanog in human bone marrow derived mesenchymal stem cells maintains their expansion and differentiation capabilities. , 2008, Experimental cell research.

[3]  Shulan Tian,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[4]  T. Ichisaka,et al.  Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2007, Cell.

[5]  H. Ohgushi,et al.  Tissue-engineered approach for the treatment of steroid-induced osteonecrosis of the femoral head: transplantation of autologous mesenchymal stem cells cultured with beta-tricalcium phosphate ceramics and free vascularized fibula. , 2006, Artificial organs.

[6]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[7]  X. Chen,et al.  The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells , 2006, Nature Genetics.

[8]  J. Thomson,et al.  Basic Fibroblast Growth Factor Support of Human Embryonic Stem Cell Self‐Renewal , 2006, Stem cells.

[9]  H. Ohgushi,et al.  Tissue engineering approach to the treatment of bone tumors: three cases of cultured bone grafts derived from patients' mesenchymal stem cells. , 2006, Artificial organs.

[10]  H. Ohgushi,et al.  Tissue engineered ceramic artificial joint--ex vivo osteogenic differentiation of patient mesenchymal cells on total ankle joints for treatment of osteoarthritis. , 2005, Biomaterials.

[11]  R. Williams,et al.  Isolation of embryonic stem (ES) cells in media supplemented with recombinant leukemia inhibitory factor (LIF). , 1990, Developmental biology.

[12]  B. Thiers Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors , 2008 .

[13]  A I Caplan,et al.  Stem cell technology and bioceramics: from cell to gene engineering. , 1999, Journal of biomedical materials research.