Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Background: Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, including bone marrow, adipose, and mucosa. MSCs have the capacity for self-renewal and differentiation. Reports have been published on the systemic administration of MSCs leading to functional improvements by engraftment and differentiation, thus providing a new strategy to regenerate damaged tissues. Recently, it has become clear that MSCs possess immunomodulatory properties and can therefore be used to treat diseases. However, the therapeutic effect mechanisms of MSCs are yet to be determined. Here, we investigated these mechanisms using a medication-related osteonecrosis of the jaw (MRONJ)-like mouse model. Methods: To generate MRONJ-like characteristics, mice received intravenous zoledronate and dexamethasone two times a week. At 1 week after intravenous injection, maxillary first molars were extracted, and at 1 week after tooth extraction, MSCs were isolated from the bone marrow of the mice femurs and tibias. To compare "diseased MSCs" from MRONJ-like mice (d-MSCs) with "control MSCs" from untreated mice (c-MSCs), the isolated MSCs were analyzed by differentiation and colony-forming unit-fibroblast (CFU-F) assays and systemic transplantation of either d-MSCs or c-MSCs into MRONJ-like mice. Furthermore, we observed the exchange of cell contents among d-MSCs and c-MSCs during coculture with all combinations of each MSC type. Results: d-MSCs were inferior to c-MSCs in differentiation and CFU-F assays. Moreover, the d-MSC-treated group did not show earlier healing in MRONJ-like mice. In cocultures with any combination, MSC pairs formed cell-cell contacts and exchanged cell contents. Interestingly, the exchange among c-MSCs and d-MSCs was more frequently observed than other pairs, and d-MSCs were distinguishable from c-MSCs. Conclusions: The interaction of c-MSCs and d-MSCs, including exchange of cell contents, contributes to the treatment potential of d-MSCs. This cellular behavior might be one therapeutic mechanism used by MSCs for MRONJ.

DOI： 10.1186/s13287-016-0367-3

Language：English  

Membrane tunneling nanotubes (TNT_s) are unique intercellular structures, which enable rapid transport of various materials and rapid communication between cells present in a long distance. During osteoclastogenesis, mononuclear osteoclast precursors form abundant TNT_s in prior to cell-cell fusion. Here we introduce a protocol for detecting TNTs during osteoclastogenesis by use of live cell imaging utilizing a confocal laser microscopy. We also demonstrate a standard protocol for observation of TNTs by scanning electron microscope.

DOI： 10.1007/978-1-4939-2703-6_14

Language：English   Publishing type：Research paper (scientific journal)  

Membrane tunneling nanotubes (TNTs) are unique intercellular structures, which enable rapid transport of various materials and rapid communication between cells present in a long distance. During osteoclas-togenesis, mononuclear osteoclast precursors form abundant TNTs in prior to cell–cell fusion. Here we introduce a protocol for detecting TNTs during osteoclastogenesis by use of live cell imaging utilizing a confocal laser microscopy. We also demonstrate a standard protocol for observation of TNTs by scanning electron microscope.

DOI： 10.1007/978-1-4939-2703-6_14

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jcb.24433