Tracking of transplanted human umbilical cord-derived mesenchymal stem cells labeled with fluorescent probe in a mouse model of acute lung injury

Liu,Genglong; Lv,Haijin; An,Yuling; Wei,Xuxia; Yi,Xiaomeng; Yi,Huimin

doi:10.3892/ijmm.2018.3491

Tracking of transplanted human umbilical cord-derived mesenchymal stem cells labeled with fluorescent probe in a mouse model of acute lung injury

Authors:
- Genglong Liu
- Haijin Lv
- Yuling An
- Xuxia Wei
- Xiaomeng Yi
- Huimin Yi
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Affiliations: Surgical Intensive Care Unit, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: February 13, 2018 https://doi.org/10.3892/ijmm.2018.3491
Pages: 2527-2534
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was topreliminarily visualize the distribution of humanumbilical cord‑derivedmesenchymal stem cells (hUC‑MSCs) in treating acute lung injury (ALI) using a targeted fluorescent technique. Anovel fluorescent molecule probe was first synthesized via the specific binding of antigen and antibody in vitro to label the hUC‑MSCs. Two groups of mice, comprising a normal saline (NS)+MSC group and lipopolysaccharide (LPS)+MSC group, were subjected to optical imaging. At 4 h following ALI mouse model construction, the labeled hUC‑MSCs were transplanted into the mice in the NS+MSC group and LPS+MSC group by tail vein injection. The mice were sacrificed 30 min, 1 day, 3 days and 7 days following injection of the labeled hUC‑MSCs, and the lungs, heart, spleen, kidneys and liver were removed. The excised lungs, heart, spleen, kidneys and liver were then detected on asmall animal fluorescent imager. The fluorescent results showed that the signal intensity in the lungs of the LPS+MSC group was significantly higher, compared with that of the NS+MSC group at 30 min (3.53±0.06x10‑4, vs. 1.95±0.05x10‑4 scaled counts/sec), 1 day (36.20±0.77x10‑4, vs. 23.45±0.43x10‑4 scaled counts/sec), 3 days (11.83±0.26x10‑4, vs. 5.39±0.10x10‑4 scaled counts/sec), and 7 days (3.14±0.04x10‑4, vs. 0.00±0.00x10‑4 scaled counts/sec; all P<0.05). The fluorescence intensity in the liver of the LPS+MSC group, vs. NS+MSC group was measured at 30 min (0.00±0.00x10‑4, vs. 0.00±0.00x10‑4 scaled counts/sec); 1 day (5.53±0.08x10‑4, vs. 5.44±0.16x10‑4 scaled counts/sec); 3 days (0.00±0.00x10‑4, vs. 8.67±0.05x10‑4 scaled counts/sec); 7 days (0.00±0.00x10‑4, vs. 0.00±0.00x10‑4 scaled counts/sec). The signal intensity of the heart, spleen and kidneys was minimal. In conclusion, the novel targeted fluorescence molecular probe was suitable for tracking the distribution processes of hUC‑MSCs in treating ALI.

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1	ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L and Slutsky AS: Acute respiratory distress syndrome: The Berlin Definition. JAMA. 307:2526–2533. 2012.PubMed/NCBI
2	Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, et al: Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 315:788–800. 2016. View Article : Google Scholar : PubMed/NCBI
3	Zafar K: Incidence of acute respiratory distress syndrome. JAMA. 316:3472016. View Article : Google Scholar : PubMed/NCBI
4	Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, et al: Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 363:1107–1116. 2010. View Article : Google Scholar : PubMed/NCBI
5	Sueblinvong V and Weiss DJ: Cell therapy approaches for lung diseases: Current status. Curr Opin Pharmacol. 9:268–273. 2009. View Article : Google Scholar : PubMed/NCBI
6	Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, et al: Higher vs. lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: Systematic review and meta-analysis. JAMA. 303:865–873. 2010. View Article : Google Scholar : PubMed/NCBI
7	Prockop DJ and Oh JY: Mesenchymal stem/stromal cells (MSCs): Role as guardians of inflammation. Mol Ther. 20:14–20. 2012. View Article : Google Scholar :
8	Lv FJ, Tuan RS, Cheung KM and Leung VY: Concise review: The surface markers and identity of human mesenchymal stem cells. Stem Cells. 32:1408–1419. 2014. View Article : Google Scholar : PubMed/NCBI
9	Akram KM, Samad S, Spiteri M and Forsyth NR: Mesenchymal stem cell therapy and lung diseases. Adv Biochem Eng Biotechnol. 130:105–129. 2013.
10	Ho MS, Mei SH and Stewart DJ: The Immunomodulatory and therapeutic effects of mesenchymal stromal cells for acute lung injury and sepsis. J Cell Physiol. 230:2606–2617. 2015. View Article : Google Scholar : PubMed/NCBI
11	Shalaby SM, El-Shal AS, Abd-Allah SH, Selim AO, Selim SA, Gouda ZA, Abd El Motteleb DM, Zanfaly HE, El-Assar HM and Abdelazim S: Mesenchymal stromal cell injection protects against oxidative stress in Escherichia coli-induced acute lung injury in mice. Cytotherapy. 16:764–775. 2014. View Article : Google Scholar : PubMed/NCBI
12	Shim SH, Xia C, Zhong G, Babcock HP, Vaughan JC, Huang B, Wang X, Xu C, Bi GQ and Zhuang X: Super-resolution fluorescence imaging of organelles in live cells with photoswitchable membrane probes. Proc Natl Acad Sci USA. 109:13978–13983. 2012. View Article : Google Scholar : PubMed/NCBI
13	Chi C, Du Y, Ye J, Kou D, Qiu J, Wang J, Tian J and Chen X: Intraoperative imaging-guided cancer surgery: From current fluorescence molecular imaging methods to future multi-modality imaging technology. Theranostics. 4:1072–1084. 2014. View Article : Google Scholar : PubMed/NCBI
14	Hussain T and Nguyen QT: Molecular imaging for cancer diagnosis and surgery. Adv Drug Deliv Rev. 66:90–100. 2014. View Article : Google Scholar
15	Kim JC, Lee JL, Yoon YS, Alotaibi AM and Kim J: Utility of indocyanine-green fluorescent imaging during robot-assisted sphincter-saving surgery on rectal cancer patients. Int J Med Robot. 12:710–717. 2016. View Article : Google Scholar
16	Chi C, Zhang Q, Mao Y, Kou D, Qiu J, Ye J, Wang J, Wang Z, Du Y and Tian J: Increased precision of orthotopic and metastatic breast cancer surgery guided by matrix metalloproteinase-activatable near-infrared fluorescence probes. Sci Rep. 5:141972015. View Article : Google Scholar : PubMed/NCBI
17	Sonn GA, Behesnilian AS, Jiang ZK, Zettlitz KA, Lepin EJ, Bentolila LA, Knowles SM, Lawrence D, Wu AM and Reiter RE: Fluorescent image-guided surgery with an anti-prostate stem cell antigen (PSCA) diabody enables targeted resection of mouse prostate cancer xenografts in real time. Clin Cancer Res. 22:1403–1412. 2016. View Article : Google Scholar
18	Martinez C, Hofmann TJ, Marino R, Dominici M and Horwitz EM: Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: A novel surface marker for the identification of MSCs. Blood. 109:4245–4248. 2007. View Article : Google Scholar : PubMed/NCBI
19	Xu J, Liao W, Gu D, Liang L, Liu M, Du W, Liu P, Zhang L, Lu S, Dong C, Zhou B and Han Z: Neural ganglioside GD2 identifies a subpopulation of mesenchymal stem cells in umbilical cord. Cell Physiol Biochem. 23:415–424. 2009. View Article : Google Scholar : PubMed/NCBI
20	Jasmin, Torres AL, Nunes HM, Passipieri JA, Jelicks LA, Gasparetto EL, Spray DC, Campos de Carvalho AC and Mendez-Otero R: Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging. J Nanobiotechnology. 9:42011. View Article : Google Scholar : PubMed/NCBI
21	Camacho X, Machado CL, García MF, Gambini JP, Banchero A, Fernández M, Oddone N, Bertolini Zanatta D, Rosal C, Buchpiguel CA, et al: Technetium-99m- or Cy7-Labeled Rituximab as an Imaging Agent for Non-Hodgkin Lymphoma. Oncology. 92:229–242. 2017. View Article : Google Scholar : PubMed/NCBI
22	Pan GZ, Yang Y, Zhang J, Liu W, Wang GY, Zhang YC, Yang Q, Zhai FX, Tai Y, Liu JR, et al: Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injuries via inactivation of the MEK/ERK signaling pathway in rats. J Surg Res. 178:935–948. 2012. View Article : Google Scholar : PubMed/NCBI
23	Metildi CA, Kaushal S, Luiken GA, Talamini MA, Hoffman RM and Bouvet M: Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model. J Surg Oncol. 109:451–458. 2014. View Article : Google Scholar
24	Park JY, Hiroshima Y, Lee JY, Maawy AA, Hoffman RM and Bouvet M: MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models. PLoS One. 10:e01221002015. View Article : Google Scholar : PubMed/NCBI
25	Tai WL, Dong ZX, Zhang DD and Wang DH: Therapeutic effect of intravenous bone marrow-derived mesenchymal stem cell transplantation on early-stage LPS-induced acute lung injury in mice. Nan Fang Yi Ke Da Xue Xue Bao. 32:283–290. 2012.PubMed/NCBI
26	Li J, Li D, Liu X, Tang S and Wei F: Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats. J Inflamm (Lond). 9:332012. View Article : Google Scholar
27	He H, Liu L, Chen Q, Liu A, Cai S, Yang Y, Lu X and Qiu H: Mesenchymal stem cells overexpressing angiotensin-converting enzyme 2 rescue lipopolysaccharide-induced lung injury. Cell Transplant. 24:1699–1715. 2015. View Article : Google Scholar
28	Zhang Y, Fan S, Yao Y, Ding J, Wang Y, Zhao Z, Liao L, Li P, Zang F and Teng GJ: In vivo, near-infrared imaging of fibrin deposition in thromboembolic stroke in mice. PLoS One. 7:e302622012. View Article : Google Scholar
29	Wang XY, Ju S, Li C, Peng XG, Chen AF, Mao H and Teng GJ: Non-invasive imaging of endothelial progenitor cells in tumor neovascularization using a novel dual-modality paramagnetic/near-infrared fluorescence probe. PLoS One. 7:e505752012. View Article : Google Scholar : PubMed/NCBI
30	Yin J, Swartz TE, Zhang J, Patapoff TW, Chen B, Marhoul J, Shih N, Kabakoff B and Rahimi K: Validation of a spectral method for quantitative measurement of color in protein drug solutions. PDA J Pharm Sci Technol. 70:382–391. 2016. View Article : Google Scholar : PubMed/NCBI
31	Garbern JC and Lee RT: Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell. 12:689–698. 2013. View Article : Google Scholar : PubMed/NCBI
32	Yu DX, Marchetto MC and Gage FH: Therapeutic translation of iPSCs for treating neurological disease. Cell Stem Cell. 12:678–688. 2013. View Article : Google Scholar : PubMed/NCBI
33	Soleimani M and Nadri S: A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc. 4:102–106. 2009. View Article : Google Scholar : PubMed/NCBI
34	Lee M, Jeong SY, Ha J, Kim M, Jin HJ, Kwon SJ, Chang JW, Choi SJ, Oh W, Yang YS, et al: Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo. Biochem Biophys Res Commun. 446:983–989. 2014. View Article : Google Scholar : PubMed/NCBI
35	El Omar R, Beroud J, Stoltz JF, Menu P, Velot E and Decot V: Umbilical cord mesenchymal stem cells: The new gold standard for mesenchymal stem cell-based therapies. Tissue Eng Part B Rev. 20:523–544. 2014. View Article : Google Scholar : PubMed/NCBI
36	Maron-Gutierrez T, Silva JD, Asensi KD, Bakker-Abreu I, Shan Y, Diaz BL, Goldenberg RC, Mei SH, Stewart DJ, Morales MM, et al: Effects of mesenchymal stem cell therapy on the time course of pulmonary remodeling depend on the etiology of lung injury in mice. Crit Care Med. 41:e319–333. 2013. View Article : Google Scholar : PubMed/NCBI
37	Tong L, Zhou J, Rong L, Seeley EJ, Pan J, Zhu X, Liu J, Wang Q, Tang X, Qu J, et al: Fibroblast Growth Factor-10 (FGF-10) mobilizes lung-resident mesenchymal stem cells and protects against acute lung injury. Sci Rep. 6:216422016. View Article : Google Scholar : PubMed/NCBI
38	Nguyen PK, Riegler J and Wu JC: Stem cell imaging: From bench to bedside. Cell Stem Cell. 14:431–444. 2014. View Article : Google Scholar : PubMed/NCBI
39	Wu C, Li J, Pang P, Liu J, Zhu K, Li D, Cheng D, Chen J, Shuai X and Shan H: Polymeric vector-mediated gene transfection of MSCs for dual bioluminescent and MRI tracking in vivo. Biomaterials. 35:8249–8260. 2014. View Article : Google Scholar : PubMed/NCBI
40	Triphan SM, Breuer FA, Gensler D, Kauczor HU and Jakob PM: Oxygen enhanced lung MRI by simultaneous measurement of T1 and T2 * during free breathing using ultrashort TE. J Magn Reson Imaging. 41:1708–1714. 2015. View Article : Google Scholar
41	Gu E, Chen WY, Gu J, Burridge P and Wu JC: Molecular imaging of stem cells: Tracking survival, biodistribution, tumorigenicity, and immunogenicity. Theranostics. 2:335–345. 2012. View Article : Google Scholar : PubMed/NCBI
42	Herberts CA, Kwa MS and Hermsen HP: Risk factors in the development of stem cell therapy. J Transl Med. 9:292011. View Article : Google Scholar : PubMed/NCBI
43	Feng T, Ai X, Ong H and Zhao Y: Dual-responsive carbon dots for tumor extracellular microenvironment triggered targeting and enhanced anticancer drug delivery. ACS Appl Mater Interfaces. 8:18732–18740. 2016. View Article : Google Scholar : PubMed/NCBI
44	Landau MJ, Gould DJ and Patel KM: Advances in fluorescent-image guided surgery. Ann Transl Med. 4:3922016. View Article : Google Scholar : PubMed/NCBI
45	Lin X, Zhu H, Luo Z, Hong Y, Zhang H, Liu X, Ding H, Tian H and Yang Z: Near-infrared fluorescence imaging of non-Hodgkin's lymphoma CD20 expression using Cy7-conjugated obinutuzumab. Mol Imaging Biol. 16:877–887. 2014. View Article : Google Scholar : PubMed/NCBI
46	Wang YY, Li XZ and Wang LB: Therapeutic implications of mesenchymal stem cells in acute lung injury/acute respiratory distress syndrome. Stem Cell Res Ther. 4:452013. View Article : Google Scholar : PubMed/NCBI
47	Zhao YD, Ohkawara H, Vogel SM, Malik AB and Zhao YY: Bone marrow-derived progenitor cells prevent thrombin-induced increase in lung vascular permeability. Am J Physiol Lung Cell Mol Physiol. 298:L36–L44. 2010. View Article : Google Scholar :
48	Qin ZH, Xu JF, Qu JM, Zhang J, Sai Y, Chen CM, Wu L and Yu L: Intrapleural delivery of MSCs attenuates acute lung injury by paracrine/endocrine mechanism. J Cell Mol Med. 16:2745–2753. 2012. View Article : Google Scholar : PubMed/NCBI
49	Sohni A and Verfaillie CM: Mesenchymal stem cells migration homing and tracking. Stem Cells Int. 2013:1307632013. View Article : Google Scholar : PubMed/NCBI
50	Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T and Sasaki H: Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury. J Immunol. 172:1266–1272. 2004. View Article : Google Scholar : PubMed/NCBI
51	Liu L, He H, Liu A, Xu J, Han J, Chen Q, Hu S, Xu X, Huang Y, Guo F, et al: Therapeutic effects of bone marrow-derived mesenchymal stem cells in models of pulmonary and extrapulmonary acute lung injury. Cell Transplant. 24:2629–2642. 2015. View Article : Google Scholar : PubMed/NCBI
52	Beckett T, Loi R, Prenovitz R, Poynter M, Goncz KK, Suratt BT and Weiss DJ: Acute lung injury with endotoxin or NO2 does not enhance development of airway epithelium from bone marrow. Mol Ther. 12:680–686. 2005. View Article : Google Scholar : PubMed/NCBI
53	Mei SH, McCarter SD, Deng Y, Parker CH, Liles WC and Stewart DJ: Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med. 4:e2692007. View Article : Google Scholar : PubMed/NCBI