Prolonged transendothelial migration of human haematopoietic stem and progenitor cells (HSPCs) towards hydrogel-released SDF1.
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.
Leibniz Institute for Polymer Research Dresden, Max Bergmann Centre for Biomaterials Dresden, Dresden, Germany.
Lidia
L
Sobkow
F Philipp
FP
Seib
Ljupco
L
Prodanov
Ina
I
Kurth
Juliane
J
Drichel
Martin
M
Bornhäuser
Carsten
C
Werner
D001853:Bone Marrow; D018929:Cell Culture Techniques; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D024042:Collagen Type I; D003432:Cross-Linking Reagents / Q000737:chemistry; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006493:Heparin / Q000737:chemistry; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000494:pharmacology*; D008954:Models, Biological; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D024042:Collagen Type I; D003432:Cross-Linking Reagents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006493:Heparin