| 摘要 |
The present embodiments provide for combinations of modulators that increase hematopoietic stem cell engraftment or increase mobilization in vivo. Methods and compositions for modulating the mobilization of stem cells, particularly for promoting or increasing the mobilization of hematopoietic stem cells (HSCs) from the bone marrow to the peripheral blood are disclosed. One aspect of the invention relates to the use of a CXCR4 antagonist that act in concert with specific molar ratios of S1P receptor 1 (S1PR1) modulator agents to promote HSC mobilization. The invention also relates to methods of using these combinations of CXCR4 antagonists and S1PR1 modulator agents for enhancing the mobilization of hematopoietic stem cells when harvesting of the stem cells, for example for the treatment of diseases, disabilities or conditions whereby transplantation of such cells would be beneficial in ameliorating a symptom associated with such diseases, disabilities or conditions. Another aspect of the invention relates to the use of a CXCR4 antagonist that act in concert with different, but specific molar ratios of S1P receptor 1 (S1PR1) modulator agents to promote HSC engraftment and methods for promoting HSC engraftment in a subject in need thereof, e.g., a recipient subject of a bone marrow or HSC transplant. Methods of screening for novel agents and pharmaceutical compositions comprising these agents are also disclosed. |
