Microvascular bioengineering: a focus on pericytes

Capillaries within the microcirculation are essential for oxygen delivery and nutrient/waste exchange, among other critical functions. Microvascular bioengineering approaches have sought to recapitulate many key features of these capillary networks, with an increasing appreciation for the necessity of incorporating vascular pericytes. Here, we briefly review established and more recent insights into important aspects of pericyte identification and function within the microvasculature. We then consider the importance of including vascular pericytes in various bioengineered microvessel platforms including 3D culturing and microfluidic systems. We also discuss how vascular pericytes are a vital component in the construction of computational models that simulate microcirculation phenomena including angiogenesis, microvascular biomechanics, and kinetics of exchange across the vessel wall. In reviewing these topics, we highlight the notion that incorporating pericytes into microvascular bioengineering applications will increase their utility and accelerate the translation of basic discoveries to clinical solutions for vascular-related pathologies.

[1]  H. Gerhardt,et al.  Endothelial cells dynamically compete for the tip cell position during angiogenic sprouting , 2010, Nature Cell Biology.

[2]  M. N. Nakatsu,et al.  Optimized fibrin gel bead assay for the study of angiogenesis. , 2007, Journal of visualized experiments : JoVE.

[3]  U. Landegren,et al.  Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. , 2003, Genes & development.

[4]  R. Hammer,et al.  White Fat Progenitor Cells Reside in the Adipose Vasculature , 2008, Science.

[5]  J. Pober,et al.  Pericytes modulate endothelial sprouting. , 2013, Cardiovascular research.

[6]  Rebecca J Shipley,et al.  Insights into cerebral haemodynamics and oxygenation utilising in vivo mural cell imaging and mathematical modelling , 2017, Scientific Reports.

[7]  G. I. Gallicano,et al.  Microvascular tubes derived from embryonic stem cells sustain blood flow. , 2006, Stem cells and development.

[8]  A. Philippides,et al.  The role of differential VE-cadherin dynamics in cell rearrangement during angiogenesis , 2014, Nature Cell Biology.

[9]  C. Betsholtz,et al.  Visualization of vascular mural cells in developing brain using genetically labeled transgenic reporter mice , 2017, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  Holger Gerhardt,et al.  Endothelial-pericyte interactions in angiogenesis , 2003, Cell and Tissue Research.

[11]  H. Hammes,et al.  Pericyte migration : A novel mechanism of pericyte loss in experimental diabetic retinopathy , 2008 .

[12]  Marcus Fruttiger,et al.  Development of the mouse retinal vasculature: angiogenesis versus vasculogenesis. , 2002, Investigative ophthalmology & visual science.

[13]  W. Lam,et al.  Engineering "Endothelialized" Microfluidics for Investigating Vascular and Hematologic Processes Using Non-Traditional Fabrication Techniques. , 2018, Current opinion in biomedical engineering.

[14]  D. Attwell,et al.  Capillary pericytes mediate coronary no-reflow after myocardial ischaemia , 2017, eLife.

[15]  M. Sefidgar,et al.  Numerical modeling of drug delivery in a dynamic solid tumor microvasculature. , 2015, Microvascular research.

[16]  Lois E. H. Smith,et al.  Selective stimulation of VEGFR-1 prevents oxygen-induced retinal vascular degeneration in retinopathy of prematurity. , 2003, The Journal of clinical investigation.

[17]  David A Hartmann,et al.  Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain. , 2018, Cell reports.

[18]  C. Betsholtz,et al.  Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. , 2003, The Journal of clinical investigation.

[19]  H. Kurz,et al.  Neuroectodermal origin of brain pericytes and vascular smooth muscle cells , 2002, The Journal of comparative neurology.

[20]  J. Ando,et al.  Shear Stress Increases Expression of the Arterial Endothelial Marker EphrinB2 in Murine ES Cells via the VEGF-Notch Signaling Pathways , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[21]  Feilim Mac Gabhann,et al.  Applications of computational models to better understand microvascular remodelling: a focus on biomechanical integration across scales , 2015, Interface Focus.

[22]  Zhen-ping Zhu,et al.  VEGFR1–mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy , 2009, Proceedings of the National Academy of Sciences of the United States of America.

[23]  F. M. Gabhann,et al.  Systems Biology of Vascular Endothelial Growth Factors , 2008, Microcirculation.

[24]  Chyuan-Sheng Lin,et al.  PDGFRβ-P2A-CreERT2 mice: a genetic tool to target pericytes in angiogenesis , 2017, Angiogenesis.

[25]  P. Rabinovitch,et al.  Interstitial pericytes decrease in aged mouse kidneys , 2015, Aging.

[26]  Peter Carmeliet,et al.  Angiogenesis in life, disease and medicine , 2005, Nature.

[27]  I. Weissman,et al.  Pericytes are progenitors for coronary artery smooth muscle , 2015, eLife.

[28]  G. Davis,et al.  This Review Is Part of a Thematic Series on Vascular Cell Diversity, Which Includes the following Articles: Heart Valve Development: Endothelial Cell Signaling and Differentiation Molecular Determinants of Vascular Smooth Muscle Cell Diversity Endothelial/pericyte Interactions Endothelial Extracellu , 2022 .

[29]  Michael J. Cronce,et al.  Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition , 2011, Proceedings of the National Academy of Sciences.

[30]  W. Stallcup,et al.  Early Contribution of Pericytes to Angiogenic Sprouting and Tube Formation , 2004, Angiogenesis.

[31]  B. Sacchetti,et al.  Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells , 2007, Nature Cell Biology.

[32]  A. Joutel,et al.  Severity of arterial defects in the retina correlates with the burden of intracerebral haemorrhage in COL4A1‐related stroke , 2018, The Journal of pathology.

[33]  R. Kamm,et al.  Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function , 2012, Proceedings of the National Academy of Sciences.

[34]  M. Raghunath,et al.  The controversial origin of pericytes during angiogenesis - Implications for cell-based therapeutic angiogenesis and cell-based therapies. , 2018, Clinical hemorheology and microcirculation.

[35]  Walter L. Murfee,et al.  Targeting Pericytes for Angiogenic Therapies , 2014, Microcirculation.

[36]  D. Attwell,et al.  Bidirectional control of CNS capillary diameter by pericytes , 2006, Nature.

[37]  Shinichiro Kumagaya,et al.  Fluid shear stress induces arterial differentiation of endothelial progenitor cells. , 2009, Journal of applied physiology.

[38]  G. Garcı́a-Cardeña,et al.  Biomechanical activation of vascular endothelium as a determinant of its functional phenotype , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  E. Hillman Coupling mechanism and significance of the BOLD signal: a status report. , 2014, Annual review of neuroscience.

[40]  C. Betsholtz,et al.  Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. , 2011, Developmental cell.

[41]  I. Herman,et al.  Pericyte chemomechanics and the angiogenic switch: insights into the pathogenesis of proliferative diabetic retinopathy? , 2015, Investigative ophthalmology & visual science.

[42]  Triantafyllos Stylianopoulos,et al.  Reengineering the Physical Microenvironment of Tumors to Improve Drug Delivery and Efficacy: From Mathematical Modeling to Bench to Bedside. , 2018, Trends in cancer.

[43]  Herbert A. Reitsamer,et al.  Brain and Retinal Pericytes: Origin, Function and Role , 2016, Front. Cell. Neurosci..

[44]  Le Zhang,et al.  Simulating brain tumor heterogeneity with a multiscale agent-based model: Linking molecular signatures, phenotypes and expansion rate , 2006, Math. Comput. Model..

[45]  L. Kim,et al.  Retinal microangiopathy in a mouse model of inducible mural cell loss. , 2014, The American journal of pathology.

[46]  Paul A. Yates,et al.  Pericytes Derived from Adipose-Derived Stem Cells Protect against Retinal Vasculopathy , 2013, PloS one.

[47]  Holger Gerhardt,et al.  Agent-based simulation of notch-mediated tip cell selection in angiogenic sprout initialisation. , 2008, Journal of theoretical biology.

[48]  M. Messi,et al.  Pericytes at the intersection between tissue regeneration and pathology. , 2015, Clinical science.

[49]  J. Finlayson,et al.  Regulation of fibronectin and laminin synthesis by retinal capillary endothelial cells and pericytes in vitro. , 1993, Experimental eye research.

[50]  R. Muschel,et al.  Correction to ‘Estimating oxygen distribution from vasculature in three-dimensional tumour tissue’ , 2016, Journal of The Royal Society Interface.

[51]  M. N. Nakatsu,et al.  An optimized three-dimensional in vitro model for the analysis of angiogenesis. , 2008, Methods in enzymology.

[52]  Daniel J. Gould,et al.  The promotion of microvasculature formation in poly(ethylene glycol) diacrylate hydrogels by an immobilized VEGF-mimetic peptide. , 2011, Biomaterials.

[53]  G. Keller,et al.  Embryonic stem cell differentiation: emergence of a new era in biology and medicine. , 2005, Genes & development.

[54]  Stuart Egginton,et al.  Modelling capillary oxygen supply capacity in mixed muscles: capillary domains revisited. , 2014, Journal of theoretical biology.

[55]  B R Johansson,et al.  Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. , 1997, Science.

[56]  Aleksander S. Popel,et al.  The Presence of VEGF Receptors on the Luminal Surface of Endothelial Cells Affects VEGF Distribution and VEGF Signaling , 2009, PLoS Comput. Biol..

[57]  J. Chappell,et al.  Establishment and characterization of an embryonic pericyte cell line , 2018, Microcirculation.

[58]  Holger Gerhardt,et al.  Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis , 2007, Nature.

[59]  K. Tryggvason,et al.  Laminin deposition is dispensable for vasculogenesis but regulates blood vessel diameter independent of flow , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[60]  A. Alavi,et al.  Opportunities and Challenges , 1998, In Vitro Diagnostic Industry in China.

[61]  Tatiana Segura,et al.  Anchorage of VEGF to the extracellular matrix conveys differential signaling responses to endothelial cells , 2010, The Journal of cell biology.

[62]  Lars E. Borm,et al.  Molecular Architecture of the Mouse Nervous System , 2018, Cell.

[63]  Axel R. Pries,et al.  Angiogenesis: An Adaptive Dynamic Biological Patterning Problem , 2013, PLoS Comput. Biol..

[64]  M. Schwartz,et al.  Mechanotransduction in vascular physiology and atherogenesis , 2009, Nature Reviews Molecular Cell Biology.

[65]  C. Betsholtz,et al.  Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. , 1999, Development.

[66]  E. Leung,et al.  Gene transfer of antisense hypoxia inducible factor-1 α enhances the therapeutic efficacy of cancer immunotherapy , 2001, Gene Therapy.

[67]  Anjelica L Gonzalez,et al.  Human Microvascular Pericyte Basement Membrane Remodeling Regulates Neutrophil Recruitment , 2015, Microcirculation.

[68]  Bengt R. Johansson,et al.  Pericytes regulate the blood–brain barrier , 2010, Nature.

[69]  C. Betsholtz,et al.  Endothelial/Pericyte Interactions , 2005, Circulation research.

[70]  Amber N. Stratman,et al.  In vitro three dimensional collagen matrix models of endothelial lumen formation during vasculogenesis and angiogenesis. , 2008, Methods in enzymology.

[71]  Satoru Takahashi,et al.  Study of normal and pathological blood vessel morphogenesis in Flt1‐tdsRed BAC Tg mice , 2012, Genesis.

[72]  M. Messi,et al.  Type-2 pericytes participate in normal and tumoral angiogenesis. , 2014, American journal of physiology. Cell physiology.

[73]  A. Zannettino,et al.  A role for pericytes as microenvironmental regulators of human skin tissue regeneration. , 2009, The Journal of clinical investigation.

[74]  Berislav V. Zlokovic,et al.  Pericytes Control Key Neurovascular Functions and Neuronal Phenotype in the Adult Brain and during Brain Aging , 2010, Neuron.

[75]  J. Kreuger,et al.  Building blood vessels—stem cell models in vascular biology , 2007, The Journal of cell biology.

[76]  Shayn M. Peirce,et al.  Microfluidics Technologies and Approaches for Studying the Microcirculation , 2017, Microcirculation.

[77]  A. Di Polo,et al.  Capillary pericytes express α-smooth muscle actin, which requires prevention of filamentous-actin depolymerization for detection , 2018, eLife.

[78]  Dai Fukumura,et al.  Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges , 2018, Nature Reviews Clinical Oncology.

[79]  E. Lammert,et al.  Quantitative assessment of angiogenesis and pericyte coverage in human cell-derived vascular sprouts , 2017, Inflammation and Regeneration.

[80]  G. Enikolopov,et al.  Role of pericytes in skeletal muscle regeneration and fat accumulation. , 2013, Stem cells and development.

[81]  R. Gutiérrez,et al.  Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. , 2009, Histology and histopathology.

[82]  B. Lilly,et al.  NOTCH3 Expression Is Induced in Mural Cells Through an Autoregulatory Loop That Requires Endothelial-Expressed JAGGED1 , 2009, Circulation research.

[83]  Ying Sun,et al.  Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types , 2018, Scientific Data.

[84]  Janet Rossant,et al.  Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice , 1995, Nature.

[85]  John C Chappell,et al.  Local guidance of emerging vessel sprouts requires soluble Flt-1. , 2009, Developmental cell.

[86]  Roger D Kamm,et al.  3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes. , 2018, Biomaterials.

[87]  Holger Gerhardt,et al.  Lack of Pericytes Leads to Endothelial Hyperplasia and Abnormal Vascular Morphogenesis , 2001, The Journal of cell biology.

[88]  W. Rathmell,et al.  Von Hippel-Lindau mutations disrupt vascular patterning and maturation via Notch. , 2018, JCI insight.

[89]  Dean Y. Li,et al.  Photoreceptor avascular privilege is shielded by soluble VEGF receptor-1 , 2013, eLife.

[90]  Ulrich Dirnagl,et al.  Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain , 2010, Proceedings of the National Academy of Sciences.

[91]  K. Kaestner,et al.  Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development , 2008, Proceedings of the National Academy of Sciences.

[92]  Fredrik Lanner,et al.  Notch Signaling Regulates Platelet-Derived Growth Factor Receptor-β Expression in Vascular Smooth Muscle Cells , 2008, Circulation research.

[93]  S. Egginton,et al.  In VivoPericyte–Endothelial Cell Interaction during Angiogenesis in Adult Cardiac and Skeletal Muscle , 1996 .

[94]  J. Trotter,et al.  NG2 cells: Properties, progeny and origin , 2010, Brain Research Reviews.

[95]  T. Maniatis,et al.  An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex , 2014, The Journal of Neuroscience.

[96]  Shayn M Peirce,et al.  Agent‐based computational model of retinal angiogenesis simulates microvascular network morphology as a function of pericyte coverage , 2017, Microcirculation.

[97]  Allon M. Klein,et al.  Single-Cell Analysis of Experience-Dependent Transcriptomic States in Mouse Visual Cortex , 2017, Nature Neuroscience.

[98]  Sean P. Palecek,et al.  Modeling the blood-brain barrier: Beyond the endothelial cells. , 2018, Current opinion in biomedical engineering.

[99]  D. Attwell,et al.  Capillary pericytes regulate cerebral blood flow in health and disease , 2014, Nature.

[100]  B. Barres,et al.  The Mouse Blood-Brain Barrier Transcriptome: A New Resource for Understanding the Development and Function of Brain Endothelial Cells , 2010, PloS one.

[101]  D. Attwell,et al.  A role for pericytes in coronary no-reflow , 2014, Nature Reviews Cardiology.

[102]  Keith K. Fenrich,et al.  Pericytes impair capillary blood flow and motor function after chronic spinal cord injury , 2017, Nature Medicine.

[103]  Stephanie J Hachey,et al.  3D microtumors in vitro supported by perfused vascular networks , 2016, Scientific Reports.

[104]  Steven C George,et al.  A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. , 2017, Lab on a chip.

[105]  D. Brenner,et al.  Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. , 2008, The American journal of pathology.

[106]  Xiaoqin Zhu,et al.  NG2 cells generate both oligodendrocytes and gray matter astrocytes , 2007, Development.

[107]  Xueqian Wang,et al.  CNS Microvascular Pericytes Exhibit Multipotential Stem Cell Activity , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[108]  Vernella Vickerman,et al.  Design, fabrication and implementation of a novel multi-parameter control microfluidic platform for three-dimensional cell culture and real-time imaging. , 2008, Lab on a chip.

[109]  S. Badylak,et al.  A perivascular origin for mesenchymal stem cells in multiple human organs. , 2008, Cell stem cell.

[110]  T. Secomb Krogh‐Cylinder and Infinite‐Domain Models for Washout of an Inert Diffusible Solute from Tissue , 2015, Microcirculation.

[111]  R. Kaunas,et al.  Fluid shear stress modulates endothelial cell invasion into three-dimensional collagen matrices. , 2008, American journal of physiology. Heart and circulatory physiology.

[112]  P. Dore‐Duffy,et al.  Role of the CNS microvascular pericyte in the blood‐brain barrier , 1998, Journal of neuroscience research.

[113]  P. Sharpe,et al.  Molecular Programming of Perivascular Stem Cell Precursors , 2018, Stem cells.

[114]  T. Doetschman,et al.  Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. , 1988, Development.

[115]  Tan Zhang,et al.  Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner , 2014, Stem Cell Research & Therapy.

[116]  Liqun He,et al.  Analysis of the brain mural cell transcriptome , 2016, Scientific Reports.

[117]  Anna Tourovskaia,et al.  Tissue-engineered microenvironment systems for modeling human vasculature , 2014, Experimental biology and medicine.

[118]  Anjelica L Gonzalez,et al.  Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung. , 2017, JCI insight.

[119]  H. Gerhardt,et al.  Synchronization of endothelial Dll4-Notch dynamics switch blood vessels from branching to expansion , 2016, eLife.

[120]  David Attwell,et al.  Imaging pericytes and capillary diameter in brain slices and isolated retinae , 2014, Nature Protocols.

[121]  A. Eichmann,et al.  Guidance of Vascular Development: Lessons From the Nervous System , 2009, Circulation research.

[122]  Hiroshi Ito No-reflow phenomenon and prognosis in patients with acute myocardial infarction , 2006, Nature Clinical Practice Cardiovascular Medicine.

[123]  M. Fox,et al.  Multiple Retinal Axons Converge onto Relay Cells in the Adult Mouse Thalamus , 2015, Cell reports.

[124]  Holger Gerhardt,et al.  Basic and Therapeutic Aspects of Angiogenesis , 2011, Cell.

[125]  Walter L. Murfee,et al.  Perivascular Cells Along Venules Upregulate NG2 Expression During Microvascular Remodeling , 2006, Microcirculation.

[126]  C. Humpel,et al.  Platelet-derived Growth Factor Receptor-beta is Differentially Regulated in Primary Mouse Pericytes and Brain Slices. , 2016, Current neurovascular research.

[127]  D. Attwell,et al.  Pericyte-Mediated Regulation of Capillary Diameter: A Component of Neurovascular Coupling in Health and Disease , 2010, Front. Neuroenerg..

[128]  U. Landegren,et al.  Defective N-sulfation of heparan sulfate proteoglycans limits PDGF-BB binding and pericyte recruitment in vascular development. , 2007, Genes & development.

[129]  S. Gerecht,et al.  Engineering the human blood-brain barrier in vitro , 2017, Journal of Biological Engineering.

[130]  M. Majesky,et al.  Vascular smooth muscle progenitor cells: building and repairing blood vessels. , 2011, Circulation research.

[131]  Shayn M Peirce,et al.  Multiscale computational models of complex biological systems. , 2013, Annual review of biomedical engineering.

[132]  S. Charpak,et al.  Vascular Compartmentalization of Functional Hyperemia from the Synapse to the Pia , 2018, Neuron.

[133]  R. Tranquillo,et al.  Shear Conditioning of Adipose Stem Cells for Reduced Platelet Binding to Engineered Vascular Grafts. , 2018, Tissue engineering. Part A.

[134]  Koji Ando,et al.  A molecular atlas of cell types and zonation in the brain vasculature , 2018, Nature.

[135]  Arnold I Caplan,et al.  All MSCs are pericytes? , 2008, Cell stem cell.

[136]  Yu-Hsiang Hsu,et al.  In vitro perfused human capillary networks. , 2013, Tissue engineering. Part C, Methods.

[137]  R. Hammer,et al.  Vasculature White Fat Progenitor Cells Reside in the Adipose , 2008 .

[138]  J Walpole,et al.  Agent-based model of angiogenesis simulates capillary sprout initiation in multicellular networks. , 2015, Integrative biology : quantitative biosciences from nano to macro.

[139]  Jaime Grutzendler,et al.  Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes , 2015, Neuron.

[140]  Heiko Rieger,et al.  Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model , 2013, PloS one.

[141]  A. G. Guex,et al.  Pericyte Seeded Dual Peptide Scaffold with Improved Endothelialization for Vascular Graft Tissue Engineering , 2016, Advanced healthcare materials.

[142]  Jianhua Huang,et al.  A Role for VEGF as a Negative Regulator of Pericyte Function and Vessel Maturation , 2008, Nature.

[143]  B. Lilly,et al.  Evaluation of Notch3 Deficiency in Diabetes-Induced Pericyte Loss in the Retina , 2018, Journal of Vascular Research.

[144]  Philippe Soriano,et al.  PDGFRβ signaling regulates mural cell plasticity and inhibits fat development. , 2011, Developmental cell.

[145]  T. Sano,et al.  [Diabetic retinopathy]. , 2001, Nihon rinsho. Japanese journal of clinical medicine.

[146]  B. Zheng,et al.  Purification and long-term culture of multipotent progenitor cells affiliated with the walls of human blood vessels: myoendothelial cells and pericytes. , 2008, Methods in cell biology.

[147]  S. Linnarsson,et al.  Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq , 2015, Science.

[148]  A. Zarbock,et al.  Leukocyte extravasation and vascular permeability are each controlled in vivo by different tyrosine residues of VE-cadherin , 2014, Nature Immunology.

[149]  J. Chappell,et al.  Excess vascular endothelial growth factor-A disrupts pericyte recruitment during blood vessel formation , 2018, Angiogenesis.

[150]  R. Adams,et al.  Spatiotemporal endothelial cell – pericyte association in tumors as shown by high resolution 4D intravital imaging , 2018, Scientific Reports.

[151]  S. Peirce,et al.  Flt-1 (VEGFR-1) coordinates discrete stages of blood vessel formation. , 2016, Cardiovascular research.

[152]  Amber N. Stratman,et al.  Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. , 2009, Blood.

[153]  Zhen Zhao,et al.  Establishment and Dysfunction of the Blood-Brain Barrier , 2015, Cell.

[154]  Changkyun Im,et al.  A Low Permeability Microfluidic Blood-Brain Barrier Platform with Direct Contact between Perfusable Vascular Network and Astrocytes , 2017, Scientific Reports.

[155]  T. Yagi,et al.  A requirement for neuropilin-1 in embryonic vessel formation. , 1999, Development.

[156]  B. Zlokovic,et al.  Shedding of soluble platelet-derived growth factor receptor-β from human brain pericytes , 2015, Neuroscience Letters.

[157]  D. Boas,et al.  Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain , 2017, Nature Neuroscience.

[158]  L. Aiello,et al.  Vascular Endothelial Growth Factor Induces Expression of Connective Tissue Growth Factor via KDR, Flt1, and Phosphatidylinositol 3-Kinase-Akt-dependent Pathways in Retinal Vascular Cells* , 2000, The Journal of Biological Chemistry.

[159]  Prashant Mali,et al.  Self-organized vascular networks from human pluripotent stem cells in a synthetic matrix , 2013, Proceedings of the National Academy of Sciences.

[160]  J. Moake,et al.  In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology. , 2012, The Journal of clinical investigation.

[161]  R. Adams,et al.  Pericytes regulate VEGF-induced endothelial sprouting through VEGFR1 , 2017, Nature Communications.

[162]  F. Faraci,et al.  Cerebral small vessel disease: insights and opportunities from mouse models of collagen IV-related small vessel disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. , 2014, Stroke.

[163]  A. Caplan Adult mesenchymal stem cells for tissue engineering versus regenerative medicine , 2007, Journal of cellular physiology.

[164]  T. Skalak,et al.  The Role of Mechanical Stresses in Microvascular Remodeling , 1996, Microcirculation.

[165]  Lasse Evensen,et al.  Mural Cell Associated VEGF Is Required for Organotypic Vessel Formation , 2009, PloS one.

[166]  Michael J Paulsen,et al.  Rapid Self-Assembly of Bioengineered Cardiovascular Bypass Grafts From Scaffold-Stabilized, Tubular Bilevel Cell Sheets , 2018, Circulation.

[167]  B. Barres,et al.  Pericytes are required for blood–brain barrier integrity during embryogenesis , 2010, Nature.

[168]  K. Alitalo,et al.  VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia , 2003, The Journal of cell biology.

[169]  Aleksander S Popel,et al.  A systems biology view of blood vessel growth and remodelling , 2013, Journal of cellular and molecular medicine.

[170]  B. Zlokovic,et al.  Central nervous system pericytes in health and disease , 2011, Nature Neuroscience.

[171]  J. Kitajewski,et al.  Combined deficiency of Notch1 and Notch3 causes pericyte dysfunction, models CADASIL, and results in arteriovenous malformations , 2015, Scientific Reports.

[172]  P. Courtoy,et al.  Fibronectin in the microvasculature: localization in the pericyte-endothelial interstitium. , 1983, Journal of ultrastructure research.

[173]  P. Sharpe,et al.  Dual origin of mesenchymal stem cells contributing to organ growth and repair , 2011, Proceedings of the National Academy of Sciences.

[174]  M. Kern,et al.  The coronary no-reflow phenomenon: a review of mechanisms and therapies. , 2001, European heart journal.

[175]  M. Wegner,et al.  Neural crest origin of retinal and choroidal pericytes. , 2013, Investigative ophthalmology & visual science.

[176]  P. Koumoutsakos,et al.  Tumorigenesis and Neoplastic Progression Contrasting Actions of Selective Inhibitors of Angiopoietin-1 and Angiopoietin-2 on the Normalization of Tumor Blood Vessels , 2009 .

[177]  E. Masliah,et al.  Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo. , 2017, Cell stem cell.

[178]  V. Bautch,et al.  Differentiation and dynamic analysis of primitive vessels from embryonic stem cells. , 2009, Methods in molecular biology.

[179]  Paul A. Bates,et al.  Tipping the Balance: Robustness of Tip Cell Selection, Migration and Fusion in Angiogenesis , 2009, PLoS Comput. Biol..

[180]  D. Vestweber,et al.  Jcb: Article , 2022 .

[181]  David A Hartmann,et al.  Pericyte Structural Remodeling in Cerebrovascular Health and Homeostasis , 2018, Front. Aging Neurosci..

[182]  Ehsan Akbari,et al.  Microfluidic approaches to the study of angiogenesis and the microcirculation , 2017, Microcirculation.

[183]  D. Riethmacher,et al.  Progenitor cells of the testosterone-producing Leydig cells revealed , 2004, The Journal of cell biology.

[184]  B. Gómez-González,et al.  Pericytes: brain-immune interface modulators , 2014, Front. Integr. Neurosci..

[185]  D. Sims,et al.  The pericyte--a review. , 1986, Tissue & cell.

[186]  David A Hartmann,et al.  Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex , 2017, bioRxiv.

[187]  Ke-shu Xu,et al.  Cdc42 is required for cytoskeletal support of endothelial cell adhesion during blood vessel formation in mice , 2015, Development.

[188]  I. Huijbers,et al.  Pericytes promote selective vessel regression to regulate vascular patterning. , 2012, Blood.

[189]  B. Klonjkowski,et al.  Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. , 2004, Genes & development.