Identification of niche signals for proliferation of hematopoietic stem cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17378
• 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, 医学系研究科, 助教 (80631184)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 造血幹細胞 / ニッチ / 生体イメージング / 自然リンパ球

Outline of Final Research Achievements

Chemotherapy has a damaging effect on hematopoietic stem and progenitor cells (HSPCs) in bone marrow　(BM). However, once chemotherapy ends, HSPCs regenerate, a process that has remained unknown. In this study, we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from chemotherapy-induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF).
Mechanistically, IL-33 released from chemo-sensitive cells activates MyD88-mediated secretion of GM-CSF in ILC2. ILC2s may function by sensing the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.
Thus, we clarify the essential mechanism of hematopoietic recovery after bone marrow injury. These results will provide clues for better adjunct therapy aimed at early hematopoietic recovery.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

生体は元々、抗がん剤で傷ついた骨髄を再生させる能力があるが、その回復機構がどのような機序で発動するのかはよくわかっていなかった。
本研究はその再生メカニズムの一つを明らかにした。更にILC2の細胞医薬としての可能性を示した。
本研究成果は、造血幹細胞を体外で増幅させる方法の開発や、抗がん剤治療後の白血球減少症の治療法開発に役立つと考えられる。