Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix.

ABSTRACT: Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin⁺) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin⁺ cells increased myeloid differentiation. We report thresholds where autocrine vs. paracrine cues alter HSC fate transitions, and were able to selectively

SUBMITTER: Mahadik BP 

PROVIDER: S-EPMC5444543 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature