Developing a xenograft model of human vasculature in the mouse ear pinna.
Adult
Animals
Blood Vessels
/ drug effects
Drug Evaluation, Preclinical
/ methods
Ear Auricle
/ blood supply
Female
Heterografts
/ drug effects
Humans
Mice
Middle Aged
Models, Animal
Regional Blood Flow
/ drug effects
Subcutaneous Fat
/ blood supply
Tissue Culture Techniques
Transplantation, Heterologous
/ methods
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 02 2020
06 02 2020
Historique:
received:
25
04
2019
accepted:
14
01
2020
entrez:
8
2
2020
pubmed:
8
2
2020
medline:
20
11
2020
Statut:
epublish
Résumé
Humanised xenograft models allow for the analysis of human tissue within a physiological environment in vivo. However, current models often rely on the angiogenesis and ingrowth of recipient vasculature to perfuse tissues, preventing analysis of biological processes and diseases involving human blood vessels. This limits the effectiveness of xenografts in replicating human physiology and may lead to issues with translating findings into human research. We have designed a xenograft model of human vasculature to address this issue. Human subcutaneous fat was cultured in vitro to promote blood vessel outgrowth prior to implantation into immunocompromised mice. We demonstrate that implants survived, retained human vasculature and anastomosed with the circulatory system of the recipient mouse. Significantly, by performing transplants into the ear pinna, this system enabled intravital observation of xenografts by multiphoton microscopy, allowing us to visualise the steps leading to vascular cytoadherence of erythrocytes infected with the human parasite Plasmodium falciparum. This model represents a useful tool for imaging the interactions that occur within human tissues in vivo and permits visualization of blood flow and cellular recruitment in a system which is amenable to intervention for various studies in basic biology together with drug evaluation and mechanism of action studies.
Identifiants
pubmed: 32029768
doi: 10.1038/s41598-020-58650-y
pii: 10.1038/s41598-020-58650-y
pmc: PMC7004987
doi:
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2058Références
Morton, J. J., Bird, G., Refaeli, Y. & Jimeno, A. Humanized Mouse Xenograft Models: Narrowing the Tumor – Microenvironment Gap. Cancer Res. 76, 6153–6159 (2016).
doi: 10.1158/0008-5472.CAN-16-1260
pubmed: 27587540
pmcid: 27587540
Yong, K., Her, Z. & Chen, Q. Humanized Mice as Unique Tools for Human-Specific Studies. Arch. Immunol. Ther. Exp. (Warsz). 66, 245–266 (2018).
doi: 10.1007/s00005-018-0506-x
pubmed: 29411049
pmcid: 29411049
Shultz, L. D., Brehm, M. A., Garcia-martinez, J. V. & Greiner, D. L. Humanized mice for immune system investigation: progress, promise and challenges. Nat. Publ. Gr. 12, 786–798 (2012).
Saunders, M. C., Keller, J. T., Dunsker, S. B. & Mayfield, F. H. Survival of autologous fat grafts in humans and in mice. Connect Tissue Res 8, 85–91 (1981).
doi: 10.3109/03008208109152128
pubmed: 6453693
pmcid: 6453693
Geens, M. et al. Spermatogonial survival after grafting human testicular tissue to immunodeficient mice. 21, 390–396 (2006).
Holen, I., Speirs, V., Morrissey, B. & Blyth, K. In vivo models in breast cancer research: progress, challenges and future directions. Dis. Model. Mech. 10, 359–371 (2017).
doi: 10.1242/dmm.028274
pubmed: 28381598
pmcid: 28381598
Mansour, A. A. et al. An in vivo model of functional and vascularized human brain organoids. Nat. Biotechnol. 36, 432–441 (2018).
doi: 10.1038/nbt.4127
pubmed: 29658944
pmcid: 29658944
Colton, C. K. Implantable biohybrid artificial organs. Cell Transplant. 4, 415–436 (1995).
doi: 10.1177/096368979500400413
pubmed: 7582573
pmcid: 7582573
Stein, I., Neeman, M., Shweiki, D., Itan, A. & Keshet, E. Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia- induced genes. Mol. Cell. Biol. 15, 5363–5368 (1995).
doi: 10.1128/MCB.15.10.5363
pubmed: 7565686
pmcid: 7565686
Calcagni, M. et al. In vivo visualization of the origination of skin graft vasculature in a wild-type/GFP crossover model. Microvasc. Res. 82, 237–245 (2011).
doi: 10.1016/j.mvr.2011.07.003
pubmed: 21784083
pmcid: 21784083
Hylander, B. L. et al. Origin of the vasculature supporting growth of primary patient tumor xenografts. J. Transl. Med. 11, 1–14 (2013).
doi: 10.1186/1479-5876-11-110
Dong, Z. et al. Xenograft tumors vascularized with murine blood vessels may overestimate the effect of anti-tumor drugs: A pilot study. PLoS One 8, 1–8 (2013).
doi: 10.1371/annotation/bcdc57a0-1377-43a7-8336-7796533013c3
De Niz, M. et al. Intravital imaging of host-parasite interactions in skin and adipose tissues. Cell. Microbiol (2019).
Storm, J. & Craig, A. G. Pathogenesis of cerebral malaria — inflammation and cytoadherence MALARIA. Front. Cell. Infect. Microbiol. 4, 1–8 (2014).
doi: 10.3389/fcimb.2014.00100
Ito, M. et al. NOD/SCID/_yc null mouse: an excellent recipient mouse modelfor engraftment of human cells. Blood 100, 3175–3182 (2002).
doi: 10.1182/blood-2001-12-0207
pubmed: 12384415
pmcid: 12384415
Madkhali, A. M. et al. An Analysis of the Binding Characteristics of a Panel of Recently Selected ICAM-1 Binding Plasmodium falciparum Patient Isolates. PLoS One 9, 4–11 (2014).
doi: 10.1371/journal.pone.0111518
Trager, W. & Jensen, J. Human Malaria parasites in continuous culture. Science (80-.). 193, 673–676 (1976).
doi: 10.1126/science.781840
Ockenhouse, C. F. et al. Molecular Basis of Sequestration in Severe and Uncomplicated Plasmodium Falciparum Malaria: Differential Adhesion of Infected Erythrocytes to CD36 and ICAM-1. J. Infect 164, 163–169 (1991).
doi: 10.1093/infdis/164.1.163
Desruisseaux, M. S., Nagajyothi, Trujillo, M. E., Tanowitz, H. B. & Scherer, P. E. Adipocyte, adipose tissue, and infectious disease. Infect. Immun. 75, 1066–1078 (2007).
doi: 10.1128/IAI.01455-06
Koethe, J. R., Hulgan, T. & Niswender, K. Adipose tissue and immune function: A review of evidence relevant to HIV infection. J. Infect. Dis. 208, 1194–1201 (2013).
doi: 10.1093/infdis/jit324
pubmed: 23878320
pmcid: 23878320
Rojas-rodriguez, R. et al. Adipose Tissue Angiogenesis Assay. Methods of Adipose Tissue Biology, Part A 537, (Elsevier Inc., 2014).
Laschke, M. W. et al. Promoting external inosculation of prevascularised tissue constructs by pre-cultivation in an angiogenic extracellular matrix. Eur. Cells Mater. 20, 356–366 (2010).
doi: 10.22203/eCM.v020a29
Gibson, V. B. et al. A novel method to allow noninvasive, longitudinal imaging of the murine immune system in vivo. Blood 119, 1–3 (2012).
doi: 10.1182/blood-2011-09-378356
Swerlick, R. A., Lee, K. H., Wick, T. M. & Lawley, T. J. Human dermal microvascular endothelial but not human umbilical vein endothelial cells express CD36 in vivo and in vitro. J. Immunol. 148, 78–83 (1992).
pubmed: 1370173
pmcid: 1370173
Laschke, M. W. et al. Vascularisation of porous scaffolds is improved by incorporation of adipose tissue-derived microvascular fragments. Eur. Cells Mater. 24, 266–277 (2012).
doi: 10.22203/eCM.v024a19
Schechner, J. S. et al. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. PNAS 97, 9191–9196 (2000).
doi: 10.1073/pnas.150242297
pubmed: 10890921
pmcid: 10890921
Hu, Z., Rooijen, N. V. & Yang, Y. Macrophages prevent human red blood cell reconstitution in immunodeficient mice. Blood 118, 5938–5946 (2012).
doi: 10.1182/blood-2010-11-321414
Garlanda, C. & Dejana, E. Heterogeneity of Endothelial Cells. Arterioscler. Thromb. Vasc. Biol. 17, 1193–1202 (1997).
doi: 10.1161/01.ATV.17.7.1193
pubmed: 9261246
pmcid: 9261246
McCormick, C. J., Craig, A., Roberts, D., Newbold, C. I. & Berendt, A. R. Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells. J. Clin. Invest. 100, 2521–2529 (1997).
doi: 10.1172/JCI119794
pubmed: 9366566
pmcid: 9366566
Müller, A. M. et al. Expression of the endothelial markers PECAM-1, vWF, and CD34 in Vivo and in Vitro. Exp. Mol. Pathol. 72, 221–229 (2002).
doi: 10.1006/exmp.2002.2424
pubmed: 12009786
pmcid: 12009786
Motherwell, J. M., Anderson, C. R. & Murfee, W. L. Endothelial Cell Phenotypes are Maintained During Angiogenesis in Cultured Microvascular Networks. Sci. Rep. 8, 1–11 (2018).
doi: 10.1038/s41598-018-24081-z
Silverstein, R. L. & Febbraio, M. CD36, a Scavenger Receptor Involved in Immunity, Metabolism. Angiogenesis, and Behavior. Sci. Signal. 2, 1–8 (2009).
Laschke, M. W., Vollmar, B. & Menger, M. D. The dorsal skinfold chamber: Window into the dynamic interaction of biomaterials with their surrounding host tissue. Eur. Cells Mater. 22, 147–167 (2011).
doi: 10.22203/eCM.v022a12
Strangward, P. et al. A quantitative brain map of experimental cerebral malaria pathology. PLoS Pathog. 13, 1–37 (2017).
doi: 10.1371/journal.ppat.1006267
Helms, G., Dasanna, A. K., Schwarz, U. S. & Lanzer, M. Modeling cytoadhesion of Plasmodium falciparum-infected erythrocytes and leukocytes—common principles and distinctive features. FEBS Lett. 1955–1971 https://doi.org/10.1002/1873-3468.12142 (2016).
Mkumbaye, S. I. et al. The Severity of Plasmodium falciparum Infection Is Associated with Transcript Levels of var Genes Encoding Endothelial Protein C Receptor-Binding P. falciparum Erythrocyte Membrane Protein 1. Cell. Microbiol. 85, 1–14 (2017).
Ho, M., Hickey, M. J., Murray, A. G., Andonegui, G. & Kubes, P. Visualization of Plasmodium falciparum–Endothelium Interactions in Human Microvasculature: Mimicry of Leukocyte Recruitment. J. Exp. Med. 192, 1205–1212 (2000).
doi: 10.1084/jem.192.8.1205
pubmed: 11034611
pmcid: 11034611
Yipp, B. G. et al. Differential roles of CD36, ICAM-1, and p-selectin in Plasmodium falciparum cytoadherence in vivo. Microcirculation 14, 593–602 (2007).
doi: 10.1080/10739680701404705
pubmed: 17710630
pmcid: 17710630
Jervis, H. R., Sprinz, H., Johnson, A. J. & Wellde, A. T. Experimental Infection in With. Am. J. Trop. Med. Hygeine 21, 382–386 (1972).
MacPherson, G. G., Warrell, M. J., White, N. J., Looareesuwan, S. & Warrell, D. A. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am. J. Pathol. 119, 385–401 (1985).
pubmed: 3893148
pmcid: 3893148
Moxon, C. A. et al. Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children. Blood 122, 842–852 (2013).
doi: 10.1182/blood-2013-03-490219
pubmed: 23741007
pmcid: 23741007
Amaladoss, A. et al. De Novo Generated Human Red Blood Cells in Humanized Mice Support Plasmodium falciparum Infection. PLoS One 10, e0129825 (2015).
doi: 10.1371/journal.pone.0129825
pubmed: 26098918
pmcid: 26098918
Bruneval, P., Duménil, G., Michea Veloso, P., Martin, T. & Melican, K. Adhesion of Neisseria meningitidis to Dermal Vessels Leads to Local Vascular Damage and Purpura in a Humanized Mouse Model. PLoS Pathog. 9, e1003139 (2013).
doi: 10.1371/journal.ppat.1003139
pubmed: 23359320
pmcid: 23359320
Minkah, N. K., Schafer, C. & Kappe, S. H. I. Humanized Mouse Models for the Study of Human Malaria Parasite Biology, Pathogenesis, and immunity. Front. Immunol. 9 (2018).
Noonan, J. et al. In vivo multiplex molecular imaging of vascular inflammation using surface-enhanced Raman spectroscopy. Theranostics 8, 6195–6209 (2018).
doi: 10.7150/thno.28665
pubmed: 30613292
pmcid: 30613292