Tohoku University. Research Profiles

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"D" Researcher - 4 Result(s)

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Induction of Schwann cells from human mesenchymal stem cells and their application to spinal cord injury and demyelinating diseases

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Bone marrow stromal cells have great advantages since they are already applied to patients either by auto- or allo-transplantations, can be harvested in large numbers (10 million cells within several weeks) as adherent cells from bone marrow aspirates, and are with low risk of tumorigenesis. Furthermore, marrow bank is available. Likewise, mesenchymal cells harvested from umbilical cord are also easily accessible from cord bank and are a good source of mesenchymal stem cells. We have established a system to induce functional Schwann cells (peripheral glia) from human bone marrow stromal cells and umbilical cord mesenchymal cells by treating cells with a series of reagents and cytokines. This induction system successfully generates Schwann cells with very high efficiency (~97%). They were confirmed to elicit neural regeneration in peripheral nerve damages and spinal cord injury (Eur, J. Neurosci, 2001; J. Neurosurg, 2004, J. Neuropathol. Exp. Neurol, 2005, Biochem Biophys Res Commun, 2007; Tissue Eng., 2011). The efficiency and safety of induced Schwann cells were demonstrated in monkey by 1 year follow up (Exp. Neurol., 2010). Importantly, induced cells not only elicited neural regeneration in both peripheral and central nervous system, but also contributed to functional recovery by restoring myelin and saltatory conduction. Therefore, these cells are expected to be effective to demyelinating diseases as well. We hope to collaborate with companies and research groups who are willing to utilize our system.

Targeted Application(s)/Industry

Graduate School of Medicine
DEZAWA Mari, Professor Doctor of Medicine

Induction of skeletal muscle cells from human mesenchymal stem cells and their application to muscle degeneration

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Bone marrow stromal cells have great advantages since they are already applied to patients either by auto- or allo-transplantations, can be harvested in large numbers (10 million cells within several weeks) as adherent cells from bone marrow aspirates, and are with low risk of tumorigenesis. We have established a system to induce skeletal muscle cells from human bone marrow stromal cells by treating cells with cytokines followed by Notch intracellular domain gene plasmid introduction. This induction system successfully generates skeletal muscle lineage cells comprised of muscle stem cells, namely, satellite cells, as well as myoblasts and myotubes. Transplantation of satellite cells and myoblasts were effective for muscle regeneration (Science, 2005). Importantly, induced satellite cells integrated into satellite cell location and continuously contributed to muscle regeneration. Our research team is now pursuing the safety and efficiency of these induced cells by using canine muscle degeneration models. We hope to collaborate with companies and research groups who are willing to utilize our system.

Targeted Application(s)/Industry

Graduate School of Medicine
DEZAWA Mari, Professor Doctor of Medicine

Induction of Neural Cells from Human Mesenchymal Stem Cells and their Application to Neurodegenerations

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Bone marrow stromal cells have great advantages since they are already applied to patients either by auto- or allo-transplantations, can be harvested in large numbers (10 million cells within several weeks) as adherent cells from bone marrow aspirates, and are with low risk of tumorigenesis. We have established a system to induce neural precursor cells from human bone marrow stromal cells by introducing cells with Notch intracellular domain gene plasmid followed by culturing in neurosphere method. This induction system successfully generates neural precursors which were effective for stroke (J. Neuropathol. Exp. Neurol. , 2005; J Cereb Blood Flow Metab, 2009). They could be further developed into dopamine producing neurons by treating them with cytokines including GDNF (J. Clin. Invest, 2004). The efficiency and safety of induced dopamine neurons were confirmed by rat and monkey model of Parkinson's disease. Importantly, long-term survival of auto-transplanted induced dopamine neurons were verified by 11C-CFT PET scan (J. Clin. Invest, 2013).

Targeted Application(s)/Industry

We hope to collaborate with companies and research groups who are willing to utilize our system.

Graduate School of Medicine
DEZAWA Mari, Professor Doctor of Medicine

Synthesis of Biologically Active Cyclodepsipeptide Natural Products

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Cyclodepsipeptide natural products include optically active hydroxy acids as well as various unnatural amino acids and exhibit a variety of biological activity depending on the peptide sequence, chirality, and selection of the hydroxy acids. Structure-activity relationships of a synthetic library of natural products could give us significant information of not only biologically important moieties but also intact positions in the biologically active small molecules. On the basis of the former information, more potent compounds and/or peptide mimetics can be designed. The latter information can also be important for making a molecular probe that is used for exploration of a target molecule.

Targeted Application(s)/Industry

We study for combinatorial synthesis of natural product analogues using solid-phase.

Graduate School of Pharmaceutical Sciences
DOI Takayuki, Professor Doctor of Engineering