Modulation of Human CXCL12 Binding Properties to Glycosaminoglycans
To Enhance Chemotactic Gradients
Posted on 2019-09-06 - 21:29
Controlled release of active biomolecules
is an attractive approach
to modulate chemotactic gradients and accordingly the recruitment
of cells, e.g. endothelial progenitor cells to improve wound healing
or stimulate angiogenesis after myocardial infarction. Here, we developed
variants of hCXCL12, also named stromal cell-derived factor 1α,
a chemokine that activates the CXCR4 and consequently recruits tissue
specific stem and progenitor cells. hCXCL12 variants were designed
to bind to glycosaminoglycans (GAGs) with different affinities in
order to modulate its release. Sixteen analogs were recombinantly
produced, characterized, and tested for their GAG-binding property.
The most promising variants hCXCL12 K24/K27/R41/R47A and hCXCL12 Q48K
were used for release studies from starPEG-heparin-hydrogels. The
reduced GAG affinity led to a fast release of hCXCL12 K24/K27/R41/R47A,
whereas hCXCL12 Q48K was slowly released over 2 weeks due to its increased
binding strength compared to wild type hCXCL12. Migration of Jurkat
cells and early endothelial progenitor cells was proven to demonstrate
the applicability of the approach to endogenously CXCR4 expressing
cell types. Thus, this work offers new options for enhancing chemotactic
hCXCL12 gradients by a combination of native and modified hCXCL12
variants to improve and prolong the recruitment of CXCR4-positive
stem and progenitor cells to injured sites.
CITE THIS COLLECTION
DataCiteDataCite
3 Biotech3 Biotech
3D Printing in Medicine3D Printing in Medicine
3D Research3D Research
3D-Printed Materials and Systems3D-Printed Materials and Systems
4OR4OR
AAPG BulletinAAPG Bulletin
AAPS OpenAAPS Open
AAPS PharmSciTechAAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität HamburgAbhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)ABI Technik (German)
Academic MedicineAcademic Medicine
Academic PediatricsAcademic Pediatrics
Academic PsychiatryAcademic Psychiatry
Academic QuestionsAcademic Questions
Academy of Management DiscoveriesAcademy of Management Discoveries
Academy of Management JournalAcademy of Management Journal
Academy of Management Learning and EducationAcademy of Management Learning and Education
Academy of Management PerspectivesAcademy of Management Perspectives
Academy of Management ProceedingsAcademy of Management Proceedings
Academy of Management ReviewAcademy of Management Review
Spiller, Sabrina; Panitz, Nydia; Limasale, Yanuar Dwi Putra; Atallah, Passant Morsi; Schirmer, Lucas; Bellmann-Sickert, Kathrin; et al. (2019). Modulation of Human CXCL12 Binding Properties to Glycosaminoglycans
To Enhance Chemotactic Gradients. ACS Publications. Collection. https://doi.org/10.1021/acsbiomaterials.9b01139