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Cited by 53Pancreatic function and diabetesExtracellular vesicles in diseaseXenotransplantation and immune response

Exosome loaded immunomodulatory biomaterials alleviate local immune response in immunocompetent diabetic mice post islet xenotransplantation

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Mohammadi, M. Rezaa, Rodriguez, Samuel Mathew, Luong, Jennifer Cam, Li, Shiri, Cao, Rui, Alshetaiwi, Hamad, Lau, Hien, Davtyan, Hayk +7 more·2021·Communications Biology
DOI 10.1038/s42003-021-02229-4PMC PMC8175379
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Abstract

Foreign body response (FBR) to biomaterials compromises the function of implants and leads to medical complications. Here, we report a hybrid alginate microcapsule (AlgXO) that attenuated the immune response after implantation, through releasing exosomes derived from human Umbilical Cord Mesenchymal Stem Cells (XOs). Upon release, XOs suppress the local immune microenvironment, where xenotransplantation of rat islets encapsulated in AlgXO led to >170 days euglycemia in immunocompetent mouse model of Type 1 Diabetes. In vitro analyses revealed that XOs suppressed the proliferation of CD3/CD28 activated splenocytes and CD3+ T cells. Comparing suppressive potency of XOs in purified CD3+ T cells versus splenocytes, we found XOs more profoundly suppressed T cells in the splenocytes co-culture, where a heterogenous cell population is present. XOs also suppressed CD3/CD28 activated human peripheral blood mononuclear cells (PBMCs) and reduced their cytokine secretion including IL-2, IL-6, IL-12p70, IL-22, and TNFα. We further demonstrate that XOs mechanism of action is likely mediated via myeloid cells and XOs suppress both murine and human macrophages partly by interfering with NFκB pathway. We propose that through controlled release of XOs, AlgXO provide a promising new platform that could alleviate the local immune response to implantable biomaterials.

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  • Alginate microcapsules designed to release exosomes derived from umbilical cord mesenchymal stem cells induced local immune tolerance by altering signaling in multiple immune cell types.

    “Similarly, alginate microcapsules designed to release exosomes derived from umbilical cord mesenchymal stem cells were also shown to induce local immune tolerance by altering signaling in multiple immune cell types.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [109]

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  1. [1]Vegas AJ Long-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent mice Nat. Med. 2016 22 306 311 10.1038/nm.4030 26808346 PMC4825868 · DOI · Paper page
  2. [2]Mao AS Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation Proc. Natl Acad. Sci. USA 2019 116 15392 10.1073/pnas.1819415116 31311862 PMC6681761 · DOI
  3. [3]Kojima R Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment Nat. Commun. 2018 9 1305 10.1038/s41467-018-03733-8 29610454 PMC5880805 · DOI · Paper page
  4. [4]Parmar M Grealish S Henchcliffe C The future of stem cell therapies for Parkinson disease Nat. Rev. Neurosci. 2020 21 103 115 10.1038/s41583-019-0257-7 31907406 · DOI
  5. [5]Wehling M Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects Eur. J. Clin. Pharmacol. 2014 70 1159 1172 10.1007/s00228-014-1734-6 25163793 · DOI
  6. [6]Srinivasan A De Cruz P Review article: a practical approach to the clinical management of NSAID enteropathy Scand. J. Gastroenterol. 2017 52 941 947 28587496
  7. [7]Tekin Z Outcomes of pancreatic islet allotransplantation using the edmonton protocol at the University of Chicago Transpl. Direct 2016 2 e105 e105 10.1097/TXD.0000000000000609 PMC5068201 27795987 · DOI
  8. [8]Shapiro AMJ Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen N. Engl. J. Med. 2000 343 230 238 10.1056/NEJM200007273430401 10911004 · DOI · Paper page
  9. [9]Shapiro AMJ International trial of the edmonton protocol for islet transplantation N. Engl. J. Med. 2006 355 1318 1330 10.1056/NEJMoa061267 17005949 · DOI · Paper page
  10. [11]Franklin Lim, F. & Sun, A. M. Microencapsulated islets as bioartificial endocrine pancreas. Science210, 908–910 (1980). 6776628
  11. [12]Tuch BE Safety and viability of microencapsulated human islets transplanted into diabetic humans Diabetes Care 2009 32 1887 10.2337/dc09-0744 19549731 PMC2752920 · DOI
  12. [13]Basta G Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts Diabetes Care 2011 34 2406 10.2337/dc11-0731 21926290 PMC3198271 · DOI
  13. [14]Orive, G. et al. Engineering a clinically translatable bioartificial pancreas to treat type I diabetes. Trend. Biotechnol. 36, 445–456 (2018). 29455936
  14. [15]Evron Y Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply Sci. Rep. 2018 8 6508 10.1038/s41598-018-23862-w 29695723 PMC5917036 · DOI
  15. [17]Bochenek MA Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques Nat. Biomed. Eng. 2018 2 810 821 10.1038/s41551-018-0275-1 30873298 PMC6413527 · DOI · Paper page
  16. [19]de Vos P Hamel AF Tatarkiewicz K Considerations for successful transplantation of encapsulated pancreatic islets Diabetologia 2002 45 159 173 10.1007/s00125-001-0729-x 11935147 · DOI
  17. [20]Vaithilingam, V. & Tuch, B. E. Islet transplantation and encapsulation: an update on recent developments. Rev. Diabet. Stud.8, 51 (2011). PMC3143677 21720673
  18. [21]Mohammadi, M. R., Luong, J. C., Kim, G. G., Lau, H. & Lakey, J. R. T. in Handbook of Tissue Engineering Scaffolds, Vol. 1 (eds Mozafari, M., Sefat, F. & Atala, A.) (Woodhead Publishing, 2019).
  19. [22]Swanson, E. Analysis of US Food and Drug Administration breast implant postapproval studies finding an increased risk of diseases and cancer: why the conclusions are unreliable. Ann. Plast. Surg. 82, 253–254 (2019). PMC6392206 30730863
  20. [23]Headon H Kasem A Mokbel K Capsular contracture after breast augmentation: an update for clinical practice Arch. Plast. Surg. 2015 42 532 543 10.5999/aps.2015.42.5.532 26430623 PMC4579163 · DOI
  21. [27]Liu Q Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation Nat. Commun. 2019 10 5262 10.1038/s41467-019-13238-7 31748525 PMC6868136 · DOI · Paper page
  22. [28]Spasojevic, M. et al. Reduction of the inflammatory responses against alginate-poly-L-lysine microcapsules by anti-biofouling surfaces of PEG-b-PLL diblock copolymers. PLoS ONE9, e109837 (2014). PMC4209974 25347191
  23. [29]Vacanti NM Localized delivery of dexamethasone from electrospun fibers reduces the foreign body response Biomacromolecules 2012 13 3031 3038 10.1021/bm300520u 22920794 PMC3466020 · DOI
  24. [30]Hachim D LoPresti ST Yates CC Brown BN Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration Biomaterials 2017 112 95 107 10.1016/j.biomaterials.2016.10.019 27760399 PMC5121003 · DOI
  25. [31]Cannarile, M. A. et al. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J. Immunother. Cancer5, 53 (2017). PMC5514481 28716061
  26. [32]Papadopoulos KP First-in-human study of AMG 820, a monoclonal anti-colony-stimulating factor 1 receptor antibody, in patients with advanced solid tumors Clin. Cancer Res. 2017 23 5703 5710 10.1158/1078-0432.CCR-16-3261 28655795 · DOI
  27. [33]Sanchez AB CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and l-type Ca2+ channels upstream of p38 MAPK J. Neuroinflammation 2016 13 252 10.1186/s12974-016-0724-2 27664068 PMC5035480 · DOI
  28. [34]Lin JT TNFα blockade in human diseases: an overview of efficacy and safety Clin. Immunol. 2008 126 121 136 10.1016/j.clim.2007.08.013 17916445 PMC2291511 · DOI
  29. [35]Walton KL Johnson KE Harrison CA Targeting TGF-β mediated SMAD signaling for the prevention of fibrosis Front Pharm. 2017 8 461 461 10.3389/fphar.2017.00461 PMC5509761 28769795 · DOI
  30. [36]Amer, L. D. et al. Inflammation via myeloid differentiation primary response gene 88 signaling mediates the fibrotic response to implantable synthetic poly(ethylene glycol) hydrogels. Acta Biomater. 100, 105–117 (2019). PMC6980661 31568879
  31. [37]Yang D Jones KS Effect of alginate on innate immune activation of macrophages J. Biomed. Mater. Res. Part A 2009 90A 411 418 10.1002/jbm.a.32096 18523947 · DOI
  32. [38]Lawlor C Treatment of Mycobacterium tuberculosis-infected macrophages with poly(lactic-co-glycolic acid) microparticles drives NFκB and autophagy dependent bacillary killing PLoS ONE 2016 11 e0149167 10.1371/journal.pone.0149167 26894562 PMC4760758 · DOI
  33. [39]Moore, L. B. & Kyriakides, T. R. in Immune Responses to Biosurfaces (eds Lambris, J. D., Ekdahl, K. N., Ricklin, D. & Nilsson, B.) (Springer International Publishing, 2015).
  34. [40]Su VY-F Lin C-S Hung S-C Yang K-Y Mesenchymal stem cell-conditioned medium induces neutrophil apoptosis associated with inhibition of the NF-κB pathway in endotoxin-induced acute lung injury Int. J. Mol. Sci. 2019 20 2208 10.3390/ijms20092208 31060326 PMC6540353 · DOI
  35. [41]Vigo T IFN-γ orchestrates mesenchymal stem cell plasticity through the signal transducer and activator of transcription 1 and 3 and mammalian target of rapamycin pathways J. Allergy Clin. Immunol. 2017 139 1667 1676 10.1016/j.jaci.2016.09.004 27670240 · DOI
  36. [42]Chen, C.-P., Tsai, P.-S.Huang, C.-J. Antiinflammation effect of human placental multipotent mesenchymal stromal cells is mediated by prostaglandin E2 via a myeloid differentiation primary response gene 88-dependent pathway Anesthesiology 2012 117 568 579 10.1097/ALN.0b013e31826150a9 22739766 · DOI
  37. [43]Riazifar M Stem cell-derived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders ACS Nano 2019 13 6670 6688 10.1021/acsnano.9b01004 31117376 PMC6880946 · DOI · Paper page
  38. [44]Yin JQ Zhu J Ankrum JA Manufacturing of primed mesenchymal stromal cells for therapy Nat. Biomed. Eng. 2019 3 90 104 10.1038/s41551-018-0325-8 30944433 · DOI
  39. [45]Riazifar M Pone EJ Lötvall J Zhao W Stem cell extracellular vesicles: extended messages of regeneration Annu. Rev. Pharmacol. Toxicol. 2017 57 125 154 10.1146/annurev-pharmtox-061616-030146 27814025 PMC5360275 · DOI
  40. [46]Lankford KL Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord PLoS ONE 2018 13 e0190358 10.1371/journal.pone.0190358 29293592 PMC5749801 · DOI
  41. [47]Fan Y Human fetal liver mesenchymal stem cell-derived exosomes impair natural killer cell function Stem Cells Dev. 2018 28 44 55 10.1089/scd.2018.0015 30328799 · DOI
  42. [48]Burrello J Stem cell-derived extracellular vesicles and immune-modulation Front. Cell Develop. Biol. 2016 4 83 10.3389/fcell.2016.00083 PMC4992732 27597941 · DOI
  43. [49]Khare D Mesenchymal stromal cell-derived exosomes affect mRNA expression and function of B-lymphocytes Front. Immunol. 2018 9 3053 3053 10.3389/fimmu.2018.03053 30622539 PMC6308164 · DOI
  44. [50]Carreras-Planella L Monguió-Tortajada M Borràs FE Franquesa M Immunomodulatory effect of MSC on B cells is independent of secreted extracellular vesicles Front. Immunol. 2019 10 1288 10.3389/fimmu.2019.01288 31244839 PMC6563675 · DOI
  45. [51]Shigemoto-Kuroda T MSC-derived extracellular vesicles attenuate immune responses in two autoimmune murine models: type 1 diabetes and uveoretinitis Stem Cell Rep. 2017 8 1214 1225 10.1016/j.stemcr.2017.04.008 PMC5425726 28494937 · DOI
  46. [52]Hass R Kasper C Böhm S Jacobs R Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC Cell Commun. Signal 2011 9 12 12 10.1186/1478-811X-9-12 21569606 PMC3117820 · DOI
  47. [53]Sun Y Human mesenchymal stem cell derived exosomes alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and relieving β-cell destruction ACS Nano 2018 12 7613 7628 10.1021/acsnano.7b07643 30052036 · DOI
  48. [54]Matsumoto S Clinical porcine islet xenotransplantation under comprehensive regulation Transplant. Proc. 2014 46 1992 1995 10.1016/j.transproceed.2014.06.008 25131091 · DOI
  49. [55]Ekser B Bottino R Cooper DKC Clinical islet xenotransplantation: a step forward EBioMedicine 2016 12 22 23 10.1016/j.ebiom.2016.09.023 27693105 PMC5078620 · DOI
  50. [56]Rezaa Mohammadi M Rodrigez S Cao R Alexander M Lakey JRT Immune response to subcutaneous implants of alginate microcapsules Mater. Today.: Proc. 2018 5 15580 15585
  51. [57]Nie W Human mesenchymal-stem-cells-derived exosomes are important in enhancing porcine islet resistance to hypoxia Xenotransplantation 2018 25 e12405 10.1111/xen.12405 29932262 · DOI
  52. [58]Zhang B Mesenchymal stromal cell exosome-enhanced regulatory T-cell production through an antigen-presenting cell-mediated pathway Cytotherapy 2018 20 687 696 10.1016/j.jcyt.2018.02.372 29622483 · DOI
  53. [59]Bai L Effects of mesenchymal stem cell-derived exosomes on experimental autoimmune uveitis Sci. Rep. 2017 7 4323 10.1038/s41598-017-04559-y 28659587 PMC5489510 · DOI
  54. [60]Paredes-Juarez GA de Haan BJ Faas MM de Vos P The role of pathogen-associated molecular patterns in inflammatory responses against alginate based microcapsules J. Control. Release 2013 172 983 992 10.1016/j.jconrel.2013.09.009 24051034 · DOI
  55. [61]Paredes Juárez, G. A., Spasojevic, M., Faas, M. M. & de Vos, P. Immunological and technical considerations in application of alginate-based microencapsulation systems. Front. Bioeng. Biotechnol.2, 26 (2014). PMC4123607 25147785
  56. [62]Mohammadi, M. et al. Controlled release of stem cell secretome attenuates inflammatory response against implanted biomaterials. Adv. Healthc. Mater.9, e1901874 (2020). 32419390
  57. [63]Fang W Identification and activation of TLR4-mediated signalling pathways by alginate-derived guluronate oligosaccharide in RAW264.7 macrophages Sci. Rep. 2017 7 1663 10.1038/s41598-017-01868-0 28490734 PMC5431981 · DOI
  58. [65]Shi C Pamer EG Monocyte recruitment during infection and inflammation Nat. Rev. Immunol. 2011 11 762 774 10.1038/nri3070 21984070 PMC3947780 · DOI · Paper page
  59. [66]Madan R Role of leptin-mediated colonic inflammation in defense against Clostridium difficile colitis Infect. Immun. 2014 82 341 10.1128/IAI.00972-13 24166957 PMC3911837 · DOI
  60. [67]Lacey DC Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models J. Immunol. 2012 188 5752 10.4049/jimmunol.1103426 22547697 · DOI
  61. [68]Yoshimura T The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally? Cell. Mol. Immunol. 2018 15 335 345 10.1038/cmi.2017.135 29375123 PMC6052833 · DOI
  62. [69]Chung, L. et al. Interleukin 17 and senescent cells regulate the foreign body response to synthetic material implants in mice and humans. Sci. Transl. Med. 12, eaax3799 (2020). PMC7219543 32295900
  63. [70]Seong S-Y Matzinger P Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses Nat. Rev. Immunol. 2004 4 469 478 10.1038/nri1372 15173835 · DOI
  64. [71]Yesilyurt V A facile and versatile method to endow biomaterial devices with zwitterionic surface coatings Adv. Healthc. Mater. 2017 6 1601091 10.1002/adhm.201601091 PMC5322155 27976536 · DOI
  65. [74]Eslami-Kaliji F Sarafbidabad M Rajadas J Mohammadi MR Dendritic cells as targets for biomaterial-based immunomodulation ACS Biomater. Sci. Eng. 2020 6 2726 2739 10.1021/acsbiomaterials.9b01987 33463292 · DOI
  66. [77]Pacienza N In vitro macrophage assay predicts the in vivo anti-inflammatory potential of exosomes from human mesenchymal stromal cells Mol. Ther. Methods Clin. Dev. 2019 13 67 76 10.1016/j.omtm.2018.12.003 30719485 PMC6350420 · DOI
  67. [78]Lenzini, S., Bargi, R., Chung, G. & Shin, J.-W. Matrix mechanics and water permeation regulate extracellular vesicle transport. Nat. Nanotechnol.15, 217–223 (2020). PMC7075670 32066904
  68. [79]Zhang B Mesenchymal stem cells secrete immunologically active exosomes Stem Cells Dev. 2014 23 1233 1244 10.1089/scd.2013.0479 24367916 · DOI
  69. [80]de Witte SFH Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells Stem Cells 2018 36 602 615 10.1002/stem.2779 29341339 · DOI · Paper page
  70. [81]Guha M Mackman N LPS induction of gene expression in human monocytes Cell. Signal. 2001 13 85 94 10.1016/S0898-6568(00)00149-2 11257452 · DOI
  71. [82]Sommerfeld SD Interleukin-36γ–producing macrophages drive IL-17–mediated fibrosis. Science Immunology 2019 4 eaax4783 PMC7549193 31604843
  72. [83]Luckheeram, R. V., Zhou, R., Verma, A. D. & Xia, B. CD4+ T cells: differentiation and functions. J. Immun. Res.2012, 10.1155/2012/925135 (2012). PMC3312336 22474485 · DOI · Paper page
  73. [84]Acharya S Amelioration of Experimental autoimmune encephalomyelitis and DSS induced colitis by NTG-A-009 through the inhibition of Th1 and Th17 cells differentiation Sci. Rep. 2018 8 7799 10.1038/s41598-018-26088-y 29773813 PMC5958108 · DOI
  74. [85]Croft M The role of TNF superfamily members in T-cell function and diseases Nat. Rev. Immunol. 2009 9 271 285 10.1038/nri2526 19319144 PMC2737409 · DOI
  75. [86]Korn T IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3 regulatory T cells Proc. Natl Acad. Sci. USA 2008 105 18460 10.1073/pnas.0809850105 19015529 PMC2587589 · DOI
  76. [87]Lee Y Induction and molecular signature of pathogenic TH17 cells Nat. Immunol. 2012 13 991 10.1038/ni.2416 22961052 PMC3459594 · DOI · Paper page
  77. [88]Tasso R Development of sarcomas in mice implanted with mesenchymal stem cells seeded onto bioscaffolds Carcinogenesis 2008 30 150 157 10.1093/carcin/bgn234 18849298 · DOI
  78. [89]Tasso R Mesenchymal stem cells induce functionally active T-regulatory lymphocytes in a paracrine fashion and ameliorate experimental autoimmune uveitis Investigative Ophthalmol. Vis. Sci. 2012 53 786 793 10.1167/iovs.11-8211 PMC3317420 22232435 · DOI
  79. [90]English K Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25Highforkhead box P3+ regulatory T cells Clin. Exp. Immunol. 2009 156 149 160 10.1111/j.1365-2249.2009.03874.x 19210524 PMC2673753 · DOI
  80. [91]Zhang B Mesenchymal stem cells secrete immunologically active exosomes Stem Cells Dev. 2013 23 1233 1244 10.1089/scd.2013.0479 24367916 · DOI
  81. [92]Mansouri, N. et al. Mesenchymal stromal cell exosomes prevent and revert experimental pulmonary fibrosis through modulation of monocyte phenotypes. JCI Insight4, e128060 (2019). PMC6948760 31581150
  82. [93]Capcha JMC Wharton’s jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation Am. J. Physiol.-Regulatory, Integr. Comp. Physiol. 2019 318 R135 R147 10.1152/ajpregu.00098.2018 31596111 · DOI
  83. [94]Liu T Zhang L Joo D Sun S-C NF-κB signaling in inflammation Signal Transduct. Target. Ther. 2017 2 17023 10.1038/sigtrans.2017.23 29158945 PMC5661633 · DOI · Paper page
  84. [95]Moore, L. B., Sawyer, A. J., Charokopos, A., Skokos, E. A. & Kyriakides, T. R. Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces NFkappaB activation in the foreign body response. Acta Biomater.11, 37–47 (2015). PMC4278755 25242651
  85. [96]Paredes-Juarez GA de Haan BJ Faas MM de Vos P A technology platform to test the efficacy of purification of alginate Materials 2014 7 2087 2103 10.3390/ma7032087 28788557 PMC5453257 · DOI
  86. [97]Caires HR Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells J. R. Soc. Interface 2016 13 20160570 10.1098/rsif.2016.0570 27628173 PMC5046958 · DOI
  87. [98]Bi D Alginate enhances Toll-like receptor 4-mediated phagocytosis by murine RAW264.7 macrophages Int. J. Biol. Macromol. 2017 105 1446 1454 10.1016/j.ijbiomac.2017.07.129 28739412 · DOI
  88. [99]Xie M Immunoregulatory effects of stem cell-derived extracellular vesicles on immune cells Front. Immunol. 2020 11 13 13 10.3389/fimmu.2020.00013 32117221 PMC7026133 · DOI
  89. [101]Kerkelä E Adenosinergic immunosuppression by human mesenchymal stromal cells requires co-operation with T cells Stem Cells 2016 34 781 790 10.1002/stem.2280 26731338 · DOI
  90. [102]Lu L-L Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials Haematologica 2006 91 1017 1026 16870554
  91. [103]Mennan C Garcia J Roberts S Hulme C Wright K A comprehensive characterisation of large-scale expanded human bone marrow and umbilical cord mesenchymal stem cells Stem Cell Res. Ther. 2019 10 99 10.1186/s13287-019-1202-4 30885254 PMC6421680 · DOI
  92. [104]Lv FJ Tuan RS Cheung KM Leung VY Concise Review: The surface markers and identity of human mesenchymal Stem Cells Stem Cells 2014 32 1408 1419 10.1002/stem.1681 24578244 · DOI
  93. [105]Mohammadi, M. R. et al. Isolation and characterization of microvesicles from mesenchymal stem cells. Methods177, 50–57 (2019). PMC7182501 31669353
  94. [106]Rodriguez, S. et al. Characterization of chelator-mediated recovery of pancreatic islets from barium-stabilized alginate microcapsules. Xenotransplantation27, e12554 (2019). 31495985

Authors
Mohammadi, M. R., Rodriguez, S. M., Luong, J. C., Li, S., Cao, R., Alshetaiwi, H., Lau, H., Davtyan, H., Jones, M. B., Jafari, M., Kessenbrock, K., Villalta, S. A., de Vos, P., Zhao, W., & Lakey, J. R. T.
Affiliations
University of California, Irvine (US)
Corresponding author
Lakey, Jonathan R. T.
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2021-06-03
Volume
4
Issue
1
Pages
685-685
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-021-02229-4
PMC
PMC8175379
OpenAlex
W3164510048
Cited by
53
References
104
Citations by year
2026: 6 · 2025: 12 · 2024: 13 · 2023: 12 · 2022: 10
FWCI
8.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
  • National Institutes of Health
  • University of California, Irvine (P30CA‐062203)
  • National Cancer Institute (P30CA062203)
  • Chao Family Comprehensive Cancer Center (P30 CA062203)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
Keywords
exosomes, alginate microcapsules, islet xenotransplantation, type 1 diabetes, foreign body reaction, immunomodulation, human umbilical cord mesenchymal stem cells, T cell suppression, macrophage suppression, NF-κB signaling, cytokine inhibition, implantable biomaterials, islet encapsulation
MeSH terms
Animals, Cells, Cultured, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Humans, Immunity, Immunologic Factors, Mice, Inbred C57BL, Spleen, T-Lymphocytes, Transplantation, Heterologous, Cytokines, Islets of Langerhans Transplantation, Immunocompromised Host, Coculture Techniques, Mice, Rats, Exosomes, Mesenchymal Stem Cells

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