Dr Paola Campagnolo is currently Lecturer of Molecular Cardiovascular Biology in the School of Biosciences and Medicine, Faculty of Health and Medical Sciences. Paola graduated in Biotechnology at the University of Padua, Italy. She then moved to Bristol to work under the supervision of Prof Paolo Madeddu at Bristol Heart Institute. In 2009, Paola completed her PhD in Cardiovascular Biology working on the isolation of a patient derived pro-angiogenic progenitor cell population. Next, Paola joined Prof Qingbo Xu's the BHF Centre of Excellence at King's College London as a BHF Research Associate to explore the use of stem cells for the repopulation of vascular grafts. In 2013, Paola joined Prof Molly Stevens' group at the Department of Materials at Imperial College London to undertake the study of novel bio- and nano- materials for cardiovascular tissue engineering.Paola has published extensively in top journals in the field of cardiovascular biology and material science with a total of over 646 citations.Paola is part of the editorial board of Editorial Board of Cardiovascular Biologics and Regenerative Medicine (specialty section of Frontiers in Cardiovascular Medicine), act as a reviewer for several journals, including PLoSONE and ATVB and is part of the reviewing board for the French National Agency of Research and the Italian Ministry of Health.
My main research interests are (1) developing improved tissue engineered vascular grafts (2) study cell-cell and cell-material interaction in vascular cell within multicellular co-culture systems (3) long term bioreactor systems for multicellular cardiovascular constructs (4) epigenetic changes in cell-material interactions.
Within the University of Surrey:Dr Kevin Maringer (Department of Microbial Sciences, FHMS)Dr Eirini Velliou (Department of Chemical Engineering, FEPS)Dr Patrizia Camelliti (Department of Biochemical Sciences, FHMS)Dr Costantina Lekakou (Department of Mechanical Engineering, FEPS)
External collaborations:Prof Paolo Madeddu (University of Bristol)Prof Molly Stevens (Imperial College London)Prof Qingbo Xu (Kings College London)Dr Nicola Smart (University of Oxford)Dr Ciro Chiappini (King's College London)
cardiovascular regeneration is a challenging issue for regenerative
medicine. In this paper, we describe a novel mechanism
regulating induced pluripotent stem cells (iPSC) differentiation
into ECs, with a particular focus on miRNAs and their targets.
We first established a protocol using collagen IV and VEGF to
drive the functional differentiation of iPSCs into ECs and compared
the miRNA signature of differentiated and undifferentiated
cells. Among the miRNAs overrepresented in differentiated
cells, we focused on microRNA-21 (miR-21) and studied its
role in iPSC differentiation. Overexpression of miR-21 in predifferentiated
iPSCs induced EC marker up-regulation and in
vitro and in vivo capillary formation; accordingly, inhibition of
miR-21 produced the opposite effects. Importantly, miR-21
overexpression increased TGF- 2 mRNA and secreted protein
level, consistent with the strong up-regulation of TGF- 2
during iPSC differentiation. Indeed, treatment of iPSCs with
TGF -2 induced EC marker expression and in vitro tube formation.
Inhibition of SMAD3, a downstream effector of TGF -2,
strongly decreased VE-cadherin expression. Furthermore,TGF -2
neutralization and knockdown inhibited miR-21-induced EC
marker expression. Finally, we confirmed the PTEN/Akt pathway
as a direct target of miR-21, and we showed that PTEN
knockdown is required for miR-21-mediated endothelial differentiation.
In conclusion, we elucidated a novel signaling pathway
that promotes the differentiation of iPSC into functional
ECs suitable for regenerative medicine applications.
oxide nanostructures by a biocompatible antifouling
homopolymer,ACS Applied Materials & Interfaces 9 (46) pp. 40059-40069 American Chemical Society
due to their magnetic properties and biocompatibility. In clinical application, the stabilization of
these nanostructures against aggregation and non-specific interactions is typically achieved using
weakly anchored polysaccharides, with better-defined and more strongly anchored synthetic
polymers not commercially adopted due to complexity of synthesis and use. Here, we show for
the first time stabilization and biocompatibilization of iron oxide nanoparticles by a synthetic
homopolymer with strong surface anchoring and a history of clinical use in other applications,
poly(2-methacryloyloxyethy phosphorylcholine) (poly(MPC)). For the commercially important
case of spherical particles, binding of poly(MPC) to iron oxide surfaces and highly effective
individualization of magnetite nanoparticles (20 nm) are demonstrated. Next-generation highaspect
ratio nanowires (both magnetite/maghemite and core-shell iron/iron oxide) are
furthermore stabilized by poly(MPC)-coating, with nanowire cytotoxicity at large concentrations
significantly reduced. The synthesis approach is exploited to incorporate functionality into the
poly(MPC) chain is demonstrated by random copolymerization with an alkyne-containing
monomer for click-chemistry. Taking these results together, poly(MPC) homopolymers and
random copolymers offer a significant improvement over current iron oxide nanoformulations,
combining straightforward synthesis, strong surface-anchoring and well-defined molecular
tissue engineered constructs, solutions delivered to the clinic are still limited. Specifically,
the lack of mature and functional vasculature greatly limits the size and complexity of
vascular scaffold models. If tissue engineering aims to replace large portions of tissue
with the intention of repairing significant defects, a more thorough understanding of the
mechanisms and players regulating the angiogenic process is required in the field. This
review will present the current material and technological advancements addressing the
imperfect formation of mature blood vessels within tissue engineered structures.
severe dengue typified by potentially fatal microvascular leakage and hypovolaemic shock.
Blood vessels of the microvasculature are composed of a tubular structure of endothelial cells
ensheathed by perivascular cells (pericytes). Pericytes support endothelial cell barrier
formation and maintenance through paracrine and contact-mediated signalling, and are critical
to microvascular integrity. Pericyte dysfunction has been linked to vascular leakage in
noncommunicable pathologies such as diabetic retinopathy, but has never been linked to
infection-related vascular leakage. Dengue vascular leakage has been shown to result in part
from the direct action of the secreted dengue virus (DENV) non-structural protein NS1 on
endothelial cells. Using primary human vascular cells, we show here that NS1 also causes
pericyte dysfunction, and that NS1-induced endothelial hyperpermeability is more pronounced
in the presence of pericytes. Notably, NS1 specifically disrupted the ability of pericytes to
support endothelial cell function in a 3D microvascular assay, with no effect on pericyte viability
or physiology. These effects are mediated at least in part through contact-independent
paracrine signals involved in endothelial barrier maintenance by pericytes. We therefore
identify a role for pericytes in amplifying NS1-induced microvascular hyperpermeability in
severe dengue, and thus show that pericytes can play a critical role in the aetiology of an
infectious vascular leakage syndrome. These findings open new avenues of research for the
development of drugs and diagnostic assays for combating infection-induced vascular
leakage, such as severe dengue.