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Prolonged transendothelial migration of human haematopoietic stem and progenitor cells (HSPCs) towards hydrogel-released SDF1

Sobkow, Lidia and Seib, F Philipp and Prodanov, Ljupco and Kurth, Ina and Drichel, Juliane and Bornhäuser, Martin and Werner, Carsten (2011) Prolonged transendothelial migration of human haematopoietic stem and progenitor cells (HSPCs) towards hydrogel-released SDF1. Annals of Hematology, 90 (8). pp. 865-871.

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Abstract

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.