Neural stem cells (NSCs) intrinsically migrate to sites of brain tumors, and engineered NSCs offer a promising mechanism for local delivery of therapeutic agents. While many groups have observed that therapeutically modified NSCs migrate selectively to glioma foci, quantitative assessments of NSC migration efficiency and local distribution at tumor sites, as well as tumor coverage estimated for the therapeutics delivered by these NSCs, have been difficult to perform. In this article, we present a quantitative analysis of immunostained serially sectioned formalin-fixed paraffin-embedded (FFPE) brain tissue across multiple test animals, thereby providing a paradigm facilitating optimization of this and other cell-based therapies.
This study is the first to identify a role for inositol hexakisphosphate kinase 1 (IP6K1) in regulating primary mouse mesenchymal stem/stromal cell (MSC) fitness. The researchers’ data show that genetic deletion of Ip6k1 results in increased MSC yields from bone marrow, and enhances the growth, survival, hematopoiesis-supporting activity, and osteogenic potential of culture-expanded cells. Increased fitness correlated with lower intrinsic p53 protein expression and mitochondrial reactive oxygen species levels, consistent with the known sensitivity of MSCs to oxidative stress. Furthermore, pharmacological inhibition of IP6K1 in mice reversed high fat diet (HFD)-induced decreases in bone volume. Together, these studies indicate that IP6K1 influences MSC frequency and function in bone marrow by modulating responsiveness to systemic changes induced by HFD feeding, and identify IP6K1 as a therapeutic target to prevent skeletal involution in response to these conditions.
A new study describes how hypoxia induces stem-like characteristics in brain tumor cells through the modulation of the chromatin environment of pluripotency-associated genes