Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs

Background  

Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells (hESC-MSCs) have been shown to reduce myocardial ischemia/reperfusion injury in animal models. However, as hESC-MSCs are not infinitely expansible, large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes.     

Differentiation state and responses to hematopoietic growth factors of murine myeloid cells transformed by myb

Murine hematopoietic cells can be transformed in vitro by recombinant retroviruses that express the myb oncogene, and hematopoietic growth factor (HGF)-dependent myeloid cell lines can be derived from these transformed primary cells. In this study, the differentiation state and responses of myb-transformed hematopoietic cells (MTHCs) have been investigated. We find that MTHCs exhibit properties of early myeloid progenitors including synergistic responses to combinations of HGFs and expression of certain surface markers. As reported previously, MTHCs respond well to granulocyte-macrophage colony-stimulating factor (GM- CSF) but can also respond to interleukin-3 (IL-3); the response to the latter factor depends on the mouse strain from which the cells are derived. Although these single factors stimulate MTHCs, combinations of these factors with colony-stimulating factor-1 (CSF-1 or M-CSF) or Steel factor (SLF or SCF) act synergistically to promote colony formation. The surface markers expressed by MTHCs include both granulocyte-macrophage lineage specific antigens Gr-1, 7/4, F4/80, and Mac-1, as well as two antigens found on early progenitors and stem cells--Thy-1 and Sca-1 (Ly6E). Expression of the latter markers is often heterogeneous and can be modulated by the growth factors to which the cells are exposed. Finally, we show that monocytic differentiation of MTHCs can be induced by exposure to tumor necrosis factor (TNF alpha). Taken together, these results suggest that MTHCs will be a useful model for studying HGF/cytokine responses in both proliferation and differentiation.     

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Astrocytes react to brain injury in a heterogeneous manner with only a subset resuming proliferation and acquiring stem cell properties in vitro. In order to identify novel regulators of this subset, we performed genomewide expression analysis of reactive astrocytes isolated 5 days after stab wound injury from the gray matter of adult mouse cerebral cortex. The expression pattern was compared with astrocytes from intact cortex and adult neural stem cells (NSCs) isolated from the subependymal zone (SEZ). These comparisons revealed a set of genes expressed at higher levels in both endogenous NSCs and reactive astrocytes, including two lectins—Galectins 1 and 3. These results and the pattern of Galectin expression in the lesioned brain led us to examine the functional significance of these lectins in brains of mice lacking Galectins 1 and 3. Following stab wound injury, astrocyte reactivity including glial fibrillary acidic protein expression, proliferation and neurosphere‐forming capacity were found significantly reduced in mutant animals. This phenotype could be recapitulated in vitro and was fully rescued by addition of Galectin 3, but not of Galectin 1. Thus, Galectins 1 and 3 play key roles in regulating the proliferative and NSC potential of a subset of reactive astrocytes. GLIA 2015;63:2340–2361     

Revues prédatrices : une vraie menace pour la recherche médicale. 1. Identifier ces revues et comprendre leur fonctionnement

The “author-pay” model of open access publication, which appeared in 2002, allocates to the author or his institution the costs of processing articles due to the journal after acceptance, for an amount of a few hundred to several thousand euros. New publishers emerged towards the end of the 2000s, which used this model but with purely commercial objectives, offering naive authors and/or wishing to quickly expand their curriculum vitae by publications in “predatory journals”. They are characterized by aggressive e-mail solicitations, lack of ethics, lack of details about the publisher and the editorial board, poor peer review, unspecified and low fees for processing articles, a lack of indexing and the promise of rapid publication.