273
Views
7
CrossRef citations to date
0
Altmetric
Review

The role of cells and their products in respiratory drug delivery: the past, present, and future

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 1689-1702 | Received 19 Jun 2020, Accepted 21 Aug 2020, Published online: 17 Sep 2020

References

  • Bertrand N, Leroux JC. The journey of a drug-carrier in the body: an anatomo-physiological perspective. J Control Release. 2012 Jul 20;161(2):152–163.
  • Kabat M, Bobkov I, Kumar S, et al. Trends in mesenchymal stem cell clinical trials 2004–2018: is efficacy optimal in a narrow dose range? Stem Cells Transl Med. 2020 Jan;9(1):17–27.
  • Silva LHA, Antunes MA, Dos Santos CC, et al. Strategies to improve the therapeutic effects of mesenchymal stromal cells in respiratory diseases. Stem Cell Res Ther. 2018 Feb 26;9(1):45.
  • Chulpanova DS, Kitaeva KV, Tazetdinova LG, et al. Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment. Front Pharmacol. 2018 March 20;9(259). DOI:10.3389/fphar.2018.00259
  • Su Y, Xie Z, Kim GB, et al. Design strategies and applications of circulating cell-mediated drug delivery systems. ACS Biomater Sci Eng. 2015;1(4):201–217.
  • Labusca L, Herea DD, Mashayekhi K. Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives. World J Stem Cells. 2018 May 26;10(5):43–56.
  • Horie S, Gonzalez HE, Laffey JG, et al. Cell therapy in acute respiratory distress syndrome. J Thorac Dis. 2018 Sep;10(9):5607–5620.
  • Thompson M, Mei SHJ, Wolfe D, et al. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: an updated systematic review and meta-analysis. EClinicalMedicine. 2020 Feb;19:100249.
  • Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014 Mar;32(3):252–260.
  • Krueger TEG, Thorek DLJ, Denmeade SR, Isaacs JT, Brennen WN. Concise Review: Mesenchymal Stem Cell-Based Drug Delivery: The Good, the Bad, the Ugly, and the Promise. Stem Cells Transl Med. 2018;7(9):651–663. DOI:10.1002/sctm.18-0024
  • Fan XL, Zhang Y, Li X, et al. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci. 2020 Jan; 77(14): 2771–2794.21
  • Sohni A, Verfaillie CM. Mesenchymal stem cells migration homing and tracking. Stem Cells Int. 2013;2013:130763.
  • Liu H, Xue W, Ge G, et al. Hypoxic preconditioning advances CXCR4 and CXCR7 expression by activating HIF-1alpha in MSCs. Biochem Biophys Res Commun. 2010 Oct 29;401(4):509–515.
  • Ponte AL, Marais E, Gallay N, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells. 2007 Jul;25(7):1737–1745.
  • Carrero R, Cerrada I, Lledo E, et al. IL1beta induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-kappaB. Stem Cell Rev Rep. 2012 Sep;8(3):905–916.
  • Hu C, Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. J Cell Mol Med. 2018 Mar;22(3):1428–1442.
  • Cassatella MA, Mosna F, Micheletti A, et al. Toll-like receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils. Stem Cells. 2011 Jun;29(6):1001–1011.
  • Zhao X, Liu D, Gong W, et al. The toll-like receptor 3 ligand, poly(I:C), improves immunosuppressive function and therapeutic effect of mesenchymal stem cells on sepsis via inhibiting MiR-143. Stem Cells. 2014 Feb;32(2):521–533.
  • Takeda K, Webb TL, Ning F, et al. Mesenchymal stem cells recruit CCR2(+) monocytes to suppress allergic airway inflammation. J Immunol. 2018 Feb 15;200(4):1261–1269.
  • Varkouhi AK, Jerkic M, Ormesher L, et al. Extracellular vesicles from interferon-gamma-primed human umbilical cord mesenchymal stromal cells reduce escherichia coli-induced acute lung injury in rats. Anesthesiology. 2019 May;130(5):778–790.
  • Guillamat-Prats R. Current status of stem cell therapy for sepsis and acute respiratory distress syndrome. In: Loewy Z, editor. Innovations in cell research and therapy (pp. 1-12). London, UK: IntechOpen; 2019.
  • Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005 Feb 15;105(4):1815–1822.
  • Duffy MM, Ritter T, Ceredig R, et al. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther. 2011 Aug 11;2(4):34.
  • Franquesa M, Mensah FK, Huizinga R, et al. Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells. Stem Cells. 2015 Mar;33(3):880–891.
  • Luk F, Carreras-Planella L, Korevaar SS, et al. Inflammatory conditions dictate the effect of mesenchymal stem or stromal cells on B cell function. Front Immunol. 2017;8:1042.
  • Uygur B, Melikov K, Arakelyan A, et al. Syncytin 1 dependent horizontal transfer of marker genes from retrovirally transduced cells. Sci Rep. 2019 Nov 27;9(1):17637.
  • McGinley LM, McMahon J, Stocca A, et al. Mesenchymal stem cell survival in the infarcted heart is enhanced by lentivirus vector-mediated heat shock protein 27 expression. Hum Gene Ther. 2013 Oct;24(10):840–851.
  • McGinley L, McMahon J, Strappe P, et al. Lentiviral vector mediated modification of mesenchymal stem cells & enhanced survival in an in vitro model of ischaemia. Stem Cell Res Ther. 2011 Mar 7;2(2):12.
  • Xue J, Li X, Lu Y, et al. Gene-modified mesenchymal stem cells protect against radiation-induced lung injury. Mol Ther. 2013 Feb;21(2):456–465.
  • Chen YB, Lan YW, Chen LG, et al. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model. Cell Stress Chaperones. 2015 Nov;20(6):979–989.
  • Zhang X, Chen J, Xue M, et al. Overexpressing p130/E2F4 in mesenchymal stem cells facilitates the repair of injured alveolar epithelial cells in LPS-induced ARDS mice. Stem Cell Res Ther. 2019 Mar 6;10(1):74.
  • EL Andaloussi S, Mäger I, Breakefield XO, et al. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347–357. DOI:10.1038/nrd3978
  • Eleuteri S, Fierabracci A. Insights into the secretome of mesenchymal stem cells and its potential applications. Int J Mol Sci. 2019 Sep 17;20(18):4597.
  • Krasnodembskaya A, Song Y, Fang X, et al. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells. 2010 Dec;28(12):2229–2238.
  • Sutton MT, Fletcher D, Ghosh SK, et al. Antimicrobial properties of mesenchymal stem cells: therapeutic potential for cystic fibrosis infection, and treatment. Stem Cells Int. 2016;2016:5303048.
  • Song Y, Dou H, Li X, et al. Exosomal miR-146a contributes to the enhanced therapeutic efficacy of interleukin-1beta-primed mesenchymal stem cells against sepsis. Stem Cells. 2017 May;35(5):1208–1221.
  • Rosland GV, Svendsen A, Torsvik A, et al. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res. 2009 Jul 1;69(13):5331–5339.
  • Barkholt L, Flory E, Jekerle V, et al. Risk of tumorigenicity in mesenchymal stromal cell-based therapies–bridging scientific observations and regulatory viewpoints. Cytotherapy. 2013 Jul;15(7):753–759.
  • Lalu MM, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2009;138(2):e47559.
  • Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells. 2017 Apr;35(4):851–858.
  • Sung DK, Chang YS, Sung SI, et al. Antibacterial effect of mesenchymal stem cells against Escherichia coli is mediated by secretion of beta- defensin- 2 via toll- like receptor 4 signalling. Cell Microbiol. 2016 Mar;18(3):424–436.
  • Alcayaga-Miranda F, Cuenca J, Martin A, et al. Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis. Stem Cell Res Ther. 2015 Oct;16(6):199.
  • Gupta N, Krasnodembskaya A, Kapetanaki M, et al. Mesenchymal stem cells enhance survival and bacterial clearance in murine escherichia coli pneumonia. Thorax. 2012 Jun;67(6):533–539.
  • Schauber J, Dorschner RA, Yamasaki K, et al. Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli. Immunology. 2006 Aug;118(4):509–519.
  • Alcayaga-Miranda F, Cuenca J, Khoury M. Antimicrobial activity of mesenchymal stem cells: current status and new perspectives of antimicrobial peptide-based therapies. Front Immunol. 2017;8:339.
  • Burnouf T, Agrahari V, Agrahari V. Extracellular vesicles as nanomedicine: hopes and hurdles in clinical translation. Int J Nanomedicine. 2019;14:8847–8859.
  • Novak JS, Jaiswal JK, Partridge TA. The macrophage as a Trojan horse for antisense oligonucleotide delivery. Expert Opin Ther Targets. 2018 Jun;22(6):463–466.
  • Fujiwara M, Baldeschwieler JD, Grubbs RH. Receptor-mediated endocytosis of poly(acrylic acid)-conjugated liposomes by macrophages. Biochim Biophys Acta. 1996 Jan 12;1278(1):59–67.
  • Choi J, Kim HY, Ju EJ, et al. Use of macrophages to deliver therapeutic and imaging contrast agents to tumors. Biomaterials. 2012 Jun;33(16):4195–4203.
  • Beduneau A, Ma Z, Grotepas CB, et al. Facilitated monocyte-macrophage uptake and tissue distribution of superparmagnetic iron-oxide nanoparticles. PLoS One. 2009;4(2):e4343.
  • Nowacek AS, Miller RL, McMillan J, et al. NanoART synthesis, characterization, uptake, release and toxicology for human monocyte-macrophage drug delivery. Nanomedicine (Lond). 2009 Dec;4(8):903–917.
  • Clavreul A, Pourbaghi-Masouleh M, Roger E, et al. Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma therapy: a good deal? J Exp Clin Cancer Res. 2017 Sep 29;36(1):135.
  • Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol. 1999;17:593–623.
  • Doshi N, Swiston AJ, Gilbert JB, et al. Cell-based drug delivery devices using phagocytosis-resistant backpacks. Adv Mater. 2011 Mar 25;23(12):H105–9.
  • Evangelopoulos M, Yazdi IK, Acciardo S, et al. Biomimetic cellular vectors for enhancing drug delivery to the lungs. Sci Rep. 2020 Jan 13;10(1):172.
  • Krombach F, Münzing S, Allmeling AM, et al. Cell size of alveolar macrophages: an interspecies comparison. Environmental Health Perspectives. 1997 Sep;105 Suppl 5:1261–1263. DOI:10.1289/ehp.97105s51261
  • Batrakova EV, Li S, Reynolds AD, et al. A macrophage-nanozyme delivery system for Parkinson’s disease. Bioconjug Chem. 2007 Sep-Oct;18(5):1498–1506.
  • Purbhoo MA, Irvine DJ, Huppa JB, et al. T cell killing does not require the formation of a stable mature immunological synapse. Nat Immunol. 2004 5;May(5):524–530.
  • Swiston AJ, Cheng C, Um SH, et al. Surface functionalization of living cells with multilayer patches. Nano Lett. 2008 Dec;8(12):4446–4453.
  • Vasconcellos FC, Swiston AJ, Beppu MM, et al. Bioactive polyelectrolyte multilayers: hyaluronic acid mediated B lymphocyte adhesion. Biomacromolecules. 2010 Sep 13;11(9):2407–2414.
  • Ong HT, Hasegawa K, Dietz AB, et al. Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies. Gene Ther. 2007 Feb;14(4):324–333.
  • Jones RB, Mueller S, Kumari S, et al. Antigen recognition-triggered drug delivery mediated by nanocapsule-functionalized cytotoxic T-cells. Biomaterials. 2017 Feb;117:44–53.
  • Sadelain M, Brentjens R, Riviere I. The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol. 2009 Apr;21(2):215–223.
  • Pettitt D, Arshad Z, Smith J, et al. CAR-T cells: A systematic review and mixed methods analysis of the clinical trial landscape. Mol Ther. 2018 Feb 7;26(2):342–353.
  • Ihler GM, Glew RH, Schnure FW. Enzyme loading of erythrocytes. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2663–2666.
  • Diez-Silva M, Dao M, Han J, et al. Shape and Biomechanical Characteristics of Human Red Blood Cells in Health and Disease. MRS Bull. 2010;35(5):382–388. DOI:10.1557/mrs2010.571
  • Koleva L, Bovt E, Ataullakhanov F, et al. Erythrocytes as carriers: from drug delivery to biosensors. Pharmaceutics. 2020 Mar 18;12(3):276.
  • Rossi L, Serafini S, Pierige F, et al. Erythrocyte-based drug delivery. Expert Opin Drug Deliv. 2005 Mar;2(2):311–322.
  • Hu CM, Fang RH, Zhang L. Erythrocyte-inspired delivery systems. Adv Healthc Mater. 2012 Sep;1(5):537–547.
  • Sun Y, Su J, Liu G, et al. Advances of blood cell-based drug delivery systems. Eur J Pharm Sci. 2017 1; Jan(96):115–128.
  • Du Y, Chen B. Combination of drugs and carriers in drug delivery technology and its development. Drug Des Devel Ther. 2019;13:1401–1408.
  • Rossi L, Serafini S, Cenerini L, et al. Erythrocyte-mediated delivery of dexamethasone in patients with chronic obstructive pulmonary disease. Biotechnol Appl Biochem. 2001 Apr;33(2):85–89.
  • Rossi L, Castro M, D’Orio F, et al. Low doses of dexamethasone constantly delivered by autologous erythrocytes slow the progression of lung disease in cystic fibrosis patients. Blood Cells Mol Dis. 2004 Jul-Aug;33(1):57–63.
  • Tan S, Wu T, Zhang D, et al. Cell or cell membrane-based drug delivery systems. Theranostics. 2015;5(8):863–881.
  • Anselmo AC, Gupta V, Zern BJ, et al. Delivering nanoparticles to lungs while avoiding liver and spleen through adsorption on red blood cells. ACS Nano. 2013 Dec 23;7(12):11129–11137.
  • Bahmani B, Bacon D, Anvari B. Erythrocyte-derived photo-theranostic agents: hybrid nano-vesicles containing indocyanine green for near infrared imaging and therapeutic applications. Sci Rep. 2013;3:2180.
  • Gupta N, Patel B, Ahsan F. Nano-engineered erythrocyte ghosts as inhalational carriers for delivery of fasudil: preparation and characterization. Pharm Res. 2014 Jun;31(6):1553–1565.
  • Li Z, Hu S, Cheng K. Platelets and their biomimetics for regenerative medicine and cancer therapies. J Mater Chem B. 2018 Dec 7;6(45):7354–7365.
  • Xu P, Zuo H, Chen B, et al. Doxorubicin-loaded platelets as a smart drug delivery system: an improved therapy for lymphoma. Sci Rep. 2017 Feb;15(7):42632.
  • Magnani M, Rossi L. Approaches to erythrocyte-mediated drug delivery. Expert Opin Drug Deliv. 2014 May;11(5):677–687.
  • Kumar A, Glaum M, El-Badri N, et al. Initial observations of cell-mediated drug delivery to the deep lung. Cell Transplant. 2011;20(5):609–618.
  • Shamekh R, El-Badri NS, Saporta S, et al. Sertoli cells induce systemic donor-specific tolerance in xenogenic transplantation model. Cell Transplant. 2006;15(1):45–53.
  • Giovagnoli S, Mancuso F, Vannini S, et al. Microparticle-loaded neonatal porcine Sertoli cells for cell-based therapeutic and drug delivery system. J Control Release. 2014 Oct;28(192):249–261.
  • Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet. 2003 May;4(5):346–358.
  • Li Y, Huo Y, Yu L, et al. Quality control and nonclinical research on CAR-T cell products: general principles and key issues. Engineering. 2019 Feb 01;5(1):122–131.
  • Wang F, Wang Z, Tian H, et al. Biodistribution and safety assessment of bladder cancer specific recombinant oncolytic adenovirus in subcutaneous xenografts tumor model in nude mice. Curr Gene Ther. 2012 Apr 1;12(2):67–76.
  • Naso MF, Tomkowicz B, Perry WL, 3rd. Adeno-associated virus (AAV) as a vector for gene therapy. BioDrugs. 2017 Aug;31(4):317–334.
  • Ramamoorth M, Narvekar A. Non viral vectors in gene therapy- an overview. J Clin Diagn Res. 2015 Jan;9(1):GE01–6.
  • Rosenecker J, Naundorf S, Gersting SW, et al. Interaction of bronchoalveolar lavage fluid with polyplexes and lipoplexes: analysing the role of proteins and glycoproteins. J Gene Med. 2003 Jan;5(1):49–60.
  • Ferguson SW, Wang J, Lee CJ, et al. The microRNA regulatory landscape of MSC-derived exosomes: a systems view. Sci Rep. 2018 Jan 23;8(1):1419.
  • Sadikot RT, Kolanjiyil AV, Kleinstreuer C, et al. Nanomedicine for treatment of acute lung injury and acute respiratory distress syndrome. Biomed Hub. 2017 May–Aug;2(2):1–12.
  • Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008 Dec 14;60(15):1615–1626.
  • Muhamad N, Plengsuriyakarn T, Na-Bangchang K. Application of active targeting nanoparticle delivery system for chemotherapeutic drugs and traditional/herbal medicines in cancer therapy: a systematic review. Int J Nanomedicine. 2018;13:3921–3935.
  • Owens DE 3rd, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006 Jan 3;307(1):93–102.
  • Kaestner L, Scholz A, Lipp P. Conceptual and technical aspects of transfection and gene delivery. Bioorg Med Chem Lett. 2015 Mar 15;25(6):1171–1176.
  • Bruce VJ, McNaughton BR. Inside job: methods for delivering proteins to the interior of mammalian cells. Cell Chem Biol. 2017 Aug 17;24(8):924–934.
  • De Berardis B, Civitelli G, Condello M, et al. Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells. Toxicol Appl Pharmacol. 2010 Aug 1;246(3):116–127.
  • Dreaden EC, Alkilany AM, Huang X, et al. The golden age: gold nanoparticles for biomedicine. Chem Soc Rev. 2012 Apr 7;41(7):2740–2779.
  • Eatemadi A, Daraee H, Karimkhanloo H, et al. Carbon nanotubes: properties, synthesis, purification, and medical applications. Nanoscale Res Lett. 2014;9(1):393.
  • Montalti M, Prodi L, Rampazzo E, et al. Dye-doped silica nanoparticles as luminescent organized systems for nanomedicine. Chem Soc Rev. 2014 Jun 21;43(12):4243–4268.
  • Harisa GI, Badran MM, Alanazi FK, et al. An overview of nanosomes delivery mechanisms: trafficking, orders, barriers and cellular effects. Artif Cells Nanomed Biotechnol. 2018 Jun;46(4):669–679.
  • Kondiah PPD, Choonara YE, Kondiah PJ, et al. 17 - Nanocomposites for therapeutic application in multiple sclerosis. In: Inamuddin AAM, Mohammad A, editors. Applications of nanocomposite materials in drug delivery (pp. 391-408). London, UK: Elsevier; 2018.
  • Lai RC, Yeo RW, Tan KH, et al. Exosomes for drug delivery - a novel application for the mesenchymal stem cell. Biotechnol Adv. 2013 Sep-Oct;31(5):543–551.
  • Singh N, Joshi A, Verma G. Chapter 10 - Engineered nanomaterials for biomedicine: advancements and hazards. In: Grumezescu AM, editor. Engineering of nanobiomaterials: applications of nanobiomaterials (Vol. 2: pp 307-328). Norwich, NY: William Andrew Publishing; 2016.
  • Chang HI, Yeh MK. Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy. Int J Nanomedicine. 2012;7:49–60.
  • Kusuzaki K, Matsubara T, Murata H, et al. Natural extracellular nanovesicles and photodynamic molecules: is there a future for drug delivery? J Enzyme Inhib Med Chem. 2017 Dec;32(1):908–916.
  • Meers P, Neville M, Malinin V, et al. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic pseudomonas aeruginosa lung infections. J Antimicrob Chemother. 2008 Apr;61(4):859–868.
  • Clancy JP, Dupont L, Konstan MW, et al. Phase II studies of nebulised arikace in CF patients with pseudomonas aeruginosa infection. Thorax. 2013 Sep;68(9):818–825.
  • Okusanya OO, Bhavnani SM, Hammel JP, et al. Evaluation of the pharmacokinetics and pharmacodynamics of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infections using data from two phase 2 clinical studies. Antimicrob Agents Chemother. 2014 Sep;58(9):5005–5015.
  • Caimmi D, Martocq N, Trioleyre D, et al. Positive effect of liposomal amikacin for inhalation on mycobacterium abcessus in cystic fibrosis patients. Open Forum Infect Dis. 2018 Mar;5(3):ofy034.
  • Howard MD, Greineder CF, Hood ED, et al. Endothelial targeting of liposomes encapsulating SOD/catalase mimetic EUK-134 alleviates acute pulmonary inflammation. J Control Release. 2014 Mar 10;177:34–41.
  • Drummond DC, Meyer O, Hong K, et al. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev. 1999 Dec;51(4):691–743.
  • Pison U, Welte T, Giersig M, et al. Nanomedicine for respiratory diseases. Eur J Pharmacol. 2006 Mar 8;533(1–3):341–350.
  • Slack JD, Kanke M, Simmons GH, et al. Acute hemodynamic effects and blood pool kinetics of polystyrene microspheres following intravenous administration. J Pharm Sci. 1981 Jun;70(6):660–664.
  • Martin FJ, Melnik K, West T, et al. Acute toxicity of intravenously administered microfabricated silicon dioxide drug delivery particles in mice: preliminary findings. Drugs R D. 2005;6(2):71–81.
  • Ferrer MC, Shuvaev VV, Zern BJ, et al. Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation. PLoS One. 2014;9(7):e102329.
  • Xu CH, Ye PJ, Zhou YC, et al. Cell membrane-camouflaged nanoparticles as drug carriers for cancer therapy. Acta Biomater. 2020 Mar;15(105):1–14.
  • Lai P-Y, Huang R-Y, Lin S-Y, et al. Biomimetic stem cell membrane-camouflaged iron oxide nanoparticles for theranostic applications. RSC Adv. 2015;5(119):98222–98230.
  • Gao C, Lin Z, Jurado-Sanchez B, et al. Stem cell membrane-coated nanogels for highly efficient in vivo tumor targeted drug delivery. Small. 2016 Aug;12(30):4056–4062.
  • Atkinson K. The biology and therapeutic application of mesenchymal cells. Hoboken: New Jersey: John Wiley & Sons, Inc; 2017.
  • Kuriakose AE, Nguyen TP, Noukeu LC, et al. Stem Cells as Drug Delivery Vehicles. In: RL R, editor. Encyclopedia of tissue engineering and regenerative medicine. London, UK: Elsiever; 2019. p. 197–210.
  • Yanez-Mo M, Siljander PR, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.
  • Oggero S, Austin-Williams S, Norling LV. The contrasting role of extracellular vesicles in vascular inflammation and tissue repair. Front Pharmacol. 2019;10:1479.
  • Johnsen KB, Gudbergsson JM, Duroux M, et al. On the use of liposome controls in studies investigating the clinical potential of extracellular vesicle-based drug delivery systems - A commentary. J Control Release. 2018 Jan;10(269):10–14.
  • Lin Y, Wu J, Gu W, et al. Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs. Adv Sci (Weinh). 2018 Apr;5(4):1700611.
  • Varga Z, Fehér B, Kitka D, et al. Size measurement of extracellular vesicles and synthetic liposomes: the impact of the hydration shell and the protein corona. Colloids Surf B Biointerfaces. 2020 aug 01;192:111053.
  • Yamamoto T, Kosaka N, Ochiya T. Latest advances in extracellular vesicles: from bench to bedside. Sci Technol Adv Mater. 2019;20(1):746–757.
  • Piffoux M, Silva AKA, Wilhelm C, et al. Modification of extracellular vesicles by fusion with liposomes for the design of personalized biogenic drug delivery systems. ACS Nano. 2018 Jul 24;12(7):6830–6842.
  • Mendt M, Kamerkar S, Sugimoto H, et al. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight. 2018 Apr 19;3:8.
  • Raposo G, Nijman HW, Stoorvogel W, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996 Mar 1;183(3):1161–1172.
  • Zitvogel L, Regnault A, Lozier A, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med. 1998 May;4(5):594–600.
  • Thery C, Regnault A, Garin J, et al. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999 Nov 1;147(3):599–610.
  • Brown EJ, Frazier WA. Integrin-associated protein (CD47) and its ligands. Trends Cell Biol. 2001 Mar;11(3):130–135.
  • Jaiswal S, Jamieson CH, Pang WW, et al. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell. 2009 Jul 23;138(2):271–285.
  • Caplan H, Olson SD, Kumar A, et al. Mesenchymal stromal cell therapeutic delivery: translational challenges to clinical application. Front Immunol. 2019;10:1645.
  • Eggenhofer E, Benseler V, Kroemer A, et al. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion. Front Immunol. 2012;3:297.
  • Zhang W, Wang M, Tang W, et al. Nanoparticle-laden macrophages for tumor-tropic drug delivery. Adv Mater. 2018 Dec;30(50):e1805557.
  • Lee RH, Pulin AA, Seo MJ, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009 Jul 2;5(1):54–63.
  • Bacou F, Andalousi RBE, Daussin PA, et al. Transplantation of adipose tissue-derived stromal cells increases mass and functional capacity of damaged skeletal muscle. Cell Transplant. 2004 Mar;13(2):103–111.
  • Sykova E, Jendelova P, Urdzikova L, et al. Bone marrow stem cells and polymer hydrogels–two strategies for spinal cord injury repair. Cell Mol Neurobiol. 2006 Oct-Nov;26(7–8):1113–1129.
  • Walczak P, Zhang J, Gilad AA, et al. Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke. 2008 May;39(5):1569–1574.
  • Zhang D, Fan GC, Zhou X, et al. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol. 2008 Feb;44(2):281–292.
  • Gao J, Dennis JE, Muzic RF, et al. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs. 2001;169(1):12–20.
  • Islam MN, Das SR, Emin MT, et al. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med. 2012 Apr 15;18(5):759–765.
  • Jackson MV, Morrison TJ, Doherty DF, et al. Mitochondrial transfer via tunneling nanotubes is an important mechanism by which mesenchymal stem cells enhance macrophage phagocytosis in the in vitro and in vivo models of ARDS. Stem Cells. 2016 Aug;34(8):2210–2223.
  • Devaney J, Horie S, Masterson C, et al. Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat. Thorax. 2015 Jul;70(7):625–635.
  • Hayes M, Curley GF, Masterson C, et al. Mesenchymal stromal cells are more effective than the MSC secretome in diminishing injury and enhancing recovery following ventilator-induced lung injury. Intensive Care Med Exp. 2015 Dec;3(1):29.
  • Ionescu L, Byrne RN, van Haaften T, et al. Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Am J Physiol Lung Cell Mol Physiol. 2012 Dec 1;303(11):L967–77.
  • Scarfe L, Taylor A, Sharkey J, et al. Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration. Stem Cell Res Ther. 2018 Nov 28;9(1):332.
  • Cardenes N, Aranda-Valderrama P, Carney JP, et al. Cell therapy for ARDS: efficacy of endobronchial versus intravenous administration and biodistribution of MAPCs in a large animal model. BMJ Open Respir Res. 2019;6(1):e000308.
  • Frohlich E, Mercuri A, Wu S, et al. Measurements of deposition, lung surface area and lung fluid for simulation of inhaled compounds. Front Pharmacol. 2016;7:181.
  • Hagerman JK, Hancock KE, Klepser ME. Aerosolised antibiotics: a critical appraisal of their use. Expert Opin Drug Deliv. 2006 Jan;3(1):71–86.
  • Palmer LB. Aerosolized antibiotics in the intensive care unit. Clin Chest Med. 2011 Sep;32(3):559–574.
  • Ari A. Ultrasonic, and mesh nebulizers: an evaluation of nebulizers for better clinical outcomes. Eurasian J Pulmonol. 2014;16:1–7.
  • Pirooznia N, Hasannia S, Lotfi AS, et al. Encapsulation of alpha-1 antitrypsin in PLGA nanoparticles: in vitro characterization as an effective aerosol formulation in pulmonary diseases. J Nanobiotechnology. 2012 May 20;10(1):20.
  • Vencken S, Foged C, Ramsey JM, et al. Nebulised lipid-polymer hybrid nanoparticles for the delivery of a therapeutic anti-inflammatory microRNA to bronchial epithelial cells. ERJ Open Res. 2019 Apr;5(2). DOI:10.1183/23120541.00161-2018
  • Averyanov A, Konoplyannikov A, Zabozlaev F, et al. Comparative effects of inhaled and intravenous mesenchymal stem cells in bleomycin-induced pulmonary fibrosis in rabbits. European Respiratory Society Annual Congress 2013; Barcelona: European Respiratory Journal.
  • Aver’yanov AV, Konoplyannikov AG, Antonov NS, et al. Survival of mesenchymal stem cells in different methods of nebulization. Bull Exp Biol Med. 2018 Mar;164(4):576–578.
  • Pritchard JN, Hatley RH, Denyer J, et al. Mesh nebulizers have become the first choice for new nebulized pharmaceutical drug developments. Ther Deliv. 2018 Feb;9(2):121–136.
  • Kim SY, Burgess JK, Wang Y, et al. Atomized human amniotic mesenchymal stromal cells for direct delivery to the airway for treatment of lung injury. J Aerosol Med Pulm Drug Deliv. 2016 Dec;29(6):514–524.
  • McCarthy SD, Horgan E, Ali A, et al. Nebulized mesenchymal stem cell derived conditioned medium retains antibacterial properties against clinical pathogen isolates. J Aerosol Med Pulm Drug Deliv. Jun;33(3):140-152.
  • Dinh PC, Paudel D, Brochu H, et al. Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis. Nat Commun. 2020 Feb 28;11(1):1064.
  • Palomba R, Parodi A, Evangelopoulos M, et al. Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability. Sci Rep. 2016 Oct;5(6):34422.
  • Ju Z, Sun W. Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles. Drug Deliv. 2017 Nov;24(1):1898–1908.
  • Zdanowicz M, Chroboczek J. Virus-like particles as drug delivery vectors. Acta Biochim Pol. 2016;63(3):469–473.
  • Kempen PJ, Greasley S, Parker KA, et al. Theranostic mesoporous silica nanoparticles biodegrade after pro-survival drug delivery and ultrasound/magnetic resonance imaging of stem cells. Theranostics. 2015;5(6):631–642.
  • Guru A, Post RJ, Ho YY, et al. Making Sense of Optogenetics. Int J Neuropsychopharmacol. 2015 Jul 25;18(11):pyv079.
  • Roth BL. DREADDs for neuroscientists. Neuron. 2016 Feb 17;89(4):683–694.
  • Kimbrel EA, Lanza R. Next-generation stem cells — ushering in a new era of cell-based therapies. Nat Rev Drug Discov. 2020 Jul;19(7) 463-479.
  • Balachandran B, Yuana Y. Extracellular vesicles-based drug delivery system for cancer treatment. Cogent Med. 2019 Jan 01;6(1):1635806.
  • Demetzos C, Kavatzikidou P, Pippa N, et al. Nanosimilars: looking for a new and dynamic regulatory “astrolabe” inspired system. AAPS PharmSciTech. 2020 Jan 13;21(2):65.
  • Halamoda-Kenzaoui B, Holzwarth U, Roebben G, et al. Mapping of the available standards against the regulatory needs for nanomedicines. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2019 Jan;11(1):e1531.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.