Therapeutic interactions between mesenchymal stem cells for healing medication-related osteonecrosis of the jaw

Yuri Matsuura, Ikiru Atsuta, Yasunori Ayukawa, Takayoshi Yamaza, Ryosuke Kondo, Akira Takahashi, Nobuyuki Ueda, Wakana Oshiro, Yoshihiro Tsukiyama, Kiyoshi Koyano

研究成果: Contribution to journalArticle査読

8 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号119
ジャーナルStem Cell Research and Therapy
7
1
DOI
出版ステータス出版済み - 8 17 2016

All Science Journal Classification (ASJC) codes

  • 医学(その他)
  • 分子医療
  • 生化学、遺伝学、分子生物学(その他)
  • 細胞生物学

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