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Blood and immune cell engineering: Cytoskeletal contractility and nuclear rheology impact cell lineage and localization
Author(s) -
Shin JaeWon,
Discher Dennis E.
Publication year - 2015
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201400166
Subject(s) - stem cell , biology , microbiology and biotechnology , immune system , progenitor cell , cytoskeleton , lamin , hematopoietic stem cell , haematopoiesis , immunology , cell , genetics , nucleus
Clinical success with human hematopoietic stem cell (HSC) transplantation establishes a paradigm for regenerative therapies with other types of stem cells. However, it remains generally challenging to therapeutically treat tissues after engineering of stem cells in vitro. Recent studies suggest that stem and progenitor cells sense physical features of their niches. Here, we review biophysical contributions to lineage decisions, maturation, and trafficking of blood and immune cells. Polarized cellular contractility and nuclear rheology are separately shown to be functional markers of a hematopoietic hierarchy that predict the ability of a lineage to traffic in and out of the bone marrow niche. These biophysical determinants are regulated by a set of structural molecules, including cytoplasmic myosin‐II and nuclear lamins, which themselves are modulated by a diverse range of transcriptional and post‐translational mechanisms. Small molecules that target these mechanobiological circuits, along with novel bioengineering methods, could prove broadly useful in programming blood and immune cells for therapies ranging from blood transfusions to immune attack of tumors.