ORCID Profile
0000-0001-8356-9152
Current Organisation
Netherlands Cancer Institute
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Publisher: Springer Science and Business Media LLC
Date: 27-04-2020
DOI: 10.1038/S41467-020-15817-5
Abstract: The endothelial cell adhesion molecule E-selectin is a key component of the bone marrow hematopoietic stem cell (HSC) vascular niche regulating balance between HSC self-renewal and commitment. We now report in contrast, E-selectin directly triggers signaling pathways that promote malignant cell survival and regeneration. Using acute myeloid leukemia (AML) mouse models, we show AML blasts release inflammatory mediators that upregulate endothelial niche E-selectin expression. Alterations in cell-surface glycosylation associated with oncogenesis enhances AML blast binding to E-selectin and enable promotion of pro-survival signaling through AKT/NF-κB pathways. In vivo AML blasts with highest E-selectin binding potential are 12-fold more likely to survive chemotherapy and main contributors to disease relapse. Absence (in Sele −/− hosts) or therapeutic blockade of E-selectin using small molecule mimetic GMI-1271/Uproleselan effectively inhibits this niche-mediated pro-survival signaling, d ens AML blast regeneration, and strongly synergizes with chemotherapy, doubling the duration of mouse survival over chemotherapy alone, whilst protecting endogenous HSC.
Publisher: Springer Science and Business Media LLC
Date: 16-01-2016
DOI: 10.1007/S12015-016-9643-Y
Abstract: The cornea provides two thirds of the refractive power of the eye and protection against insults such as infection and injury. The outermost tissue of the cornea is renewed by stem cells located in the limbus. Depletion or destruction of these stem cells may lead to blinding limbal stem cell deficiency (LSCD) that concerns millions of patients around the world. Innovative strategies based on adult stem cell therapies have been developed in the recent years but they are still facing numerous unresolved issues, and the long term results can be deceiving. Today there is a clear need to improve these therapies, and/or to develop new approaches for the treatment of LSCD. Here, we review the current cell-based therapies used for the treatment of ocular diseases, and discuss the potential of pluripotent stem cells (embryonic and induced pluripotent stem cells) in corneal repair. As the secretion of paracrine factors is known to have a crucial role in maintaining stem cell homeostasis and in wound repair, we also consider the therapeutic potential of a promising novel pathway, the exosomes. Exosomes are nano-sized vesicles that have the ability to transfer RNAs and proteins to recipient cells, and several studies demonstrated their role in cell protection and wound healing. Exosomes could circumvent the hurdles of stem-cell based approaches, and they could become a strong candidate as an alternative therapy for ocular surface diseases.
Publisher: Frontiers Media SA
Date: 24-07-2020
Location: France
No related grants have been discovered for Johanna Erbani.