Prolonged transendothelial migration of human haematopoietic stem and progenitor cells (HSPCs) towards hydrogel-released SDF1
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The therapeutic success of haematopoetic stem and progenitor cell (HSPC) transplantation is critically dependent on HSPC engraftment in the bone marrow. Gradients of stromal cell-derived factor 1 (SDF1) direct HSPC homing, both in vitro and in vivo. Potentially, regulating the delivery levels of exogenous SDF1 applied to the bone marrow could augment HSPC engraftment. Thus, the aim of the present study was to revise the ability of biocompatible hydrogels to direct HSPC migration in vitro. The delivery system of choice is based on heparin cross-linked with collagen1. We confirm that hydrogel is capable of trapping and releasing SDF1 and using it to generate a protein gradient in transendothelial migration experiments. The use of SDF1-functionalised hydrogel to produce a chemokine gradient revealed, sustained and increased HSPC migration when compared to diffusible SDF1 controls. In conclusion, regulating SDF1 gradients with heparin-containing hydrogels may offer valuable options to direct site-specific migration of HSPC.
KeywordsHSPC SDF1 Heparin Collagen Migration Gradient
This work was supported by the Leibniz Association (Senatswettbewerb LS, MB and CW), the Deutsche Forschungsgemeinschaft, ″Collaborative Research Centre: Cells into tissues- stem cell and progenitor commitment and interactions during tissue formation″ (SFB 655, Dresden, FPS, MB and CW) and the Centre for Regenerative Therapies Dresden (DFG Research Centre and Cluster of Excellence).
Support and financial disclosure declaration
Authors declare no competing financial interests.
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