Elucidation of key signals for successful engraftment of transplanted bone marrow cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16114
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Osaka University
• Principal Investigator: Sudo Takao 大阪大学, 生命機能研究科, 助教 (80631184)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 造血幹細胞 / 造血幹細胞ニッチ / 生体イメージング

Outline of Final Research Achievements

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, thereby promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. In this study, we show that injured BM environments support the recovery of HSPCs from 5-fluorouracil (5-FU)-induced stress by secreting growth factors.
Mechanistically, IL-33 released from chemo-sensitive BM cells activates MyD88-mediated secretion of growth factors. Thus, injured BM environments may function by ‘sensing’ the damaged BM spaces and subsequently supporting hematopoietic recovery under stress conditions.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から、「抗癌剤投与後の骨髄機能の回復はどのような機序で起こるのか」という疑問の一端を解決した。本研究結果は、骨髄移植の際に、骨髄を破壊する前処置が造血幹細胞の生着に促進的に働くこと理由を説明するモデルとも捉えられる。
本研究から得られた結果は、今後造血幹細胞移植ソースとしての造血幹細胞を体外増幅する際に必要な情報をもたらしうる、という点で意義が大きい。