Abstract
Accurate modeling of angiogenesis in vitro is essential for guiding the preclinical development of novel anti-angiogenic agents and treatment strategies. The formation of new blood vessels is a multifactorial and multi-stage process dependent upon paracrine factors produced by stromal cells in the local microenvironment. Mesenchymal stem cells (MSCs) are multipotent cells in adults that can be recruited to sites of inflammation and tissue damage where they aid in wound healing through regenerative, trophic, and immunomodulatory properties. Primary stromal cultures derived from human bone marrow, normal prostate, or prostate cancer tissue are highly enriched in MSCs and stromal progenitors. Using conditioned media from these primary cultures, a robust pro-angiogenic response was observed in a physiologically-relevant three-dimensional fibrin matrix assay. To evaluate the utility of this assay, the allosteric HDAC4 inhibitor tasquinimod and the anti-VEGF monoclonal antibody bevacizumab were used as model compounds with distinct mechanisms of action. While both agents had a profound inhibitory effect on endothelial sprouting, only bevacizumab induced significant regression of established vessels. Additionally, the pro-angiogenic properties of MSCs derived from prostate cancer patients provides further evidence that selective targeting of this population may be of therapeutic benefit.
Highlights
Angiogenesis is an essential event in a diverse array of physiologic and pathologic processes, including organogenesis, wound healing, and cancer
The pro-angiogenic properties of Mesenchymal stem cells (MSCs) derived from prostate cancer patients provides further evidence that selective targeting of this population may be of therapeutic benefit
This process is commonly studied in tissue culture using human umbilical vein endothelial cells (HUVECs), including the previously described 3D assay in which cells attached to a gelatin-coated dextran bead are embedded in a fibrin matrix (Figure 1)
Summary
Angiogenesis is an essential event in a diverse array of physiologic and pathologic processes, including organogenesis, wound healing, and cancer. The requirement for stromal-derived paracrine factors in the initiation and maturation of vessels has been demonstrated using primary stromal cultures in a three-dimensional (3D) in vitro fibrin matrix co-culture system [2,3,4,5]. This assay was originally developed by Hughes et al and has several advantages over alternative methodologies to assess angiogenic potential in that it accurately recapitulates each of the major physiologic stages necessary for new vessel formation; resulting in a complex, multicellular capillary network of branched and interconnected lumens [3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
