2004 Fiscal Year Final Research Report Summary
Gene expression profiling and evaluation of physiologic functions in monocyte-derived multipotential cells
| Project/Area Number |
15390307
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Keio University |
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Principal Investigator |
KUWANA Masataka Keio University, Institute for Advanced Medical Research, Assistant Professor, 医学部, 講師 (50245479)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Yasuo Keio University, Department of Medicine, Professor, 医学部, 教授 (00110883)
ASAHI Atsuko Keio University, Institute for Advanced Medical Research, Assistant, 医学部, 助手 (50348265)
SUZUKI Shigeaki Keio University, Department of Medicine, Instructor, 医学部, 助手 (50276242)
INOKO Hidetoshi Tokai University, Department of Molecular Life Science, Professor, 医学部, 教授 (10101932)
INOUE Takafumi Tokyo University, Institute of Medical Science, Department of Basic Medical Sciences, Associate Professor, 医科学研究所, 助教授 (10262081)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Regenerative medicine / Monocyte / Differentiation / Trans-differentiation / Stem cell / Genechip |
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| Research Abstract |
We have recently identified a novel CD14^+ CD45^+ CD34^+ type I collagen^+ cell fraction derived from human circulating CD14^+ monocytes, monocyte-derived multipotential cell (MOMC), which contains progenitors capable of differentiating into a variety of mesenchymal cells, including bone, cartilage, fat and skeletal muscle. To identify MOMC-related genes potentially involved in multipotentiality, gene expression profiling was compared between circulating monocytes and MOMCs by genechip analysis. Six genes, including DLG3, MyoX, SEPT3, EFNA3, ATF-1, and SAP30, were identified as genes preferentially expressed in the MOMC among monocyte-lineage cell types. Next, human MOMCs co-cultivated with primary cultures of rat cardiomyocytes or neurons underwent expression of cardiomyocyte- or neuron-specific transcription factors and structural proteins, respectively. MOMC-derived cardiomyocyte-like cells represented spontaneously beating, and exhibited electrophysiological properties of ventricul
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ar myocytes. MOMCs treated with angiogenic factors underwent a change in their morphology to caudated and upregulated expression of endothelium-specific molecules. Functional characteristics were indistinguishable between MOMC-derived endothelial cells and mature endothelial cells. In xenogenic transplantation studies using a SCID mouse model, in which syngeneic colon carcinoma were injected subcutaneously with human MOMCs, co-transplantation with MOMCs markedly promoted blood vessel formation. More than 50% of blood vessels incorporated human MOMC-derived endothelial cells. Finally, MOMCs were able to expand human hematopoietic stem cells to 100-fold in vitro in 2 weeks, but failed to maintain longterm-culture-initiating cells.
The cellular therapy using MOMCs has considerable advantages over currently proposed strategies using tissue-specific stem cells and embryonic stem cells. Circulating monocytes can be an abundant and easily accessible source for autologous cell transplantation for tissue regeneration, and the ethical dilemma of using ES cells can be bypassed. Our findings suggest that strategies to use MOMCs can be one of practical alternatives to the stem cell-based regenerative therapies. Less
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Research Products
(4 results)
