Journal
STEM CELLS
Volume 32, Issue 8, Pages 2245-2255Publisher
WILEY
DOI: 10.1002/stem.1701
Keywords
Bone marrow mesenchymal stromal/stem cells; Cadherin-11; Parathyroid hormone; Hematopoiesis
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan
- Project for Development of Innovative Research on Cancer Therapeutics from MEXT in Japan
- Ministry of Health, Labour and Welfare in Japan
- National Cancer Center Research and Development Fund [23-A-23]
- Japan Science and Technology Agency
- Japan Leukemia Research Fund
- Kyoto University Translational Research Center
- Cell Science Research Foundation
- Kobayashi Foundation for Cancer Research
- Joint Usage/Research Center of Hiroshima University Research Institute for Radiation Biology and Medicine
- Princess Takamatsu Cancer Research Fund
- Grants-in-Aid for Scientific Research [25461415, 25112706, 25430149, 24390244, 24659461] Funding Source: KAKEN
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Parathyroid hormone (PTH) stimulates hematopoiesis in mouse models. The involvement of osteoblasts in this process has been well investigated; however, the effects of PTH on human hematopoiesis and bone marrow mesenchymal stromal cells (BM-MSCs) are unclear. Here, we show that BM-MSCs contribute to the hematopoiesis-stimulating effects of PTH via upregulation of cadherin-11 (CDH11). When culture-expanded human BM-MSCs were stimulated with PTH, their ability to expand cocultured CD34(+) hematopoietic progenitor cells (HPCs) was enhanced. Furthermore, when PTH-treated BM-MSCs were subcutaneously implanted into NOD/SCID mice, the induction of hematopoietic cells was enhanced. Culture-expanded human BM-MSCs expressed CDH11, and the level of CDH11 expression increased following PTH stimulation. Depletion of CDH11 expression in BM-MSCs using small interfering RNA abolished the enhancement of HPC expansion by PTH-treated BM-MSCs. In lethally irradiated mice that underwent BM transplantation, CDH11 expression in BM-MSCs was higher and survival was better in PTH-treated mice than in control mice. The number of hematopoietic cells in BM and the number of red blood cells in peripheral blood were higher in PTH-treated mice than in control mice. Our results demonstrate that PTH stimulates hematopoiesis through promoting the upregulation of CDH11 expression in BM-MSCs, at least in part. PTH treatment may be an effective strategy to enhance the ability of BM-MSCs to support hematopoiesis.
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