Targeted transplantation of iron oxide‑labeled, adipose‑derived mesenchymal stem cells in promoting meniscus regeneration 
following a rabbit massive meniscal defect

Qi,Yiying; Yang,Zhigao; Ding,Qianhai; Zhao,Tengfei; Huang,Zhongming; Feng,Gang

doi:10.3892/etm.2015.2944

Targeted transplantation of iron oxide‑labeled, adipose‑derived mesenchymal stem cells in promoting meniscus regeneration following a rabbit massive meniscal defect

Authors:
- Yiying Qi
- Zhigao Yang
- Qianhai Ding
- Tengfei Zhao
- Zhongming Huang
- Gang Feng
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Affiliations: Department of Orthopedic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: December 16, 2015 https://doi.org/10.3892/etm.2015.2944
Pages: 458-466
Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Repair of a massive meniscal defect remains a challenge in the clinic. However, targeted magnetic cell delivery, an emerging technique, may be useful in its treatment. The present study aimed to determine the effect of targeted intra‑articular injection of superparamagnetic iron oxide (SPIO)‑labeled adipose‑derived mesenchymal stem cells (ASCs) in a rabbit model of a massive meniscal defect. ASCs may be directly labeled and almost 100% of the ASCs were labeled with SPIO after 24 h; these SPIO‑labeled ASCs may be orientated by magnet. The centrifuged SPIO‑labeled ASCs precipitations may be detected by magnetic resonance imaging (MRI). The anterior half of the medial meniscus of 18 New Zealand Rabbits was excised. After 7 days, the rabbits were randomized to injections of 2x106 SPIO‑labeled ASCs, 2x106 unlabeled ASCs or saline. Permanent magnets were fixed to the outside of the operated joints for one day, and after 6 and 12 weeks, the knee joints were examined using MRI, gross and histological observation, and Prussian blue staining. Marked hypointense artifacts caused by SPIO‑positive cells in the meniscus were detected using MRI. Histological observation revealed that the anterior portion of the meniscus was similar to the native tissue, demonstrating typical fibrochondrocytes surrounded by richer extracellular matrix in the SPIO‑ASCs group. Collagen‑rich matrix bridging the interface and the neo‑meniscus integrated well with its host meniscus. Furthermore, degenerative changes occurred in all groups, but intra‑articular injection of SPIO‑ASCs or ASCs alleviated these degenerative changes. Prussian blue staining indicated that the implanted ASCs were directly associated with the regenerated tissue. Overall, targeted intra‑articular delivery of SPIO‑ASCs promoted meniscal regeneration whilst providing protective effects from osteoarthritic damage.

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1	Fairbank TJ: Knee joint changes after meniscectomy. J Bone Joint Surg Br. 30B:664–670. 1948.PubMed/NCBI
2	Fox JM, Blazina ME and Carlson GJ: Multiphasic view of medial meniscectomy. Am J Sports Med. 7:161–164. 1979. View Article : Google Scholar : PubMed/NCBI
3	Jørgensen U, Sonne-Holm S, Lauridsen F and Rosenklint AL: Long-term follow-up of meniscectomy in athletes. A prospective longitudinal study. J Bone Joint Surg Br. 69:80–83. 1987.PubMed/NCBI
4	Sweigart MA and Athanasiou KA: Toward tissue engineering of the knee meniscus. Tissue Eng. 7:111–129. 2001. View Article : Google Scholar : PubMed/NCBI
5	Baker P, Coggon D, Reading I, Barrett D, McLaren M and Cooper C: Sports injury, occupational physical activity, joint laxity, and meniscal damage. J Rheumatol. 29:557–563. 2002.PubMed/NCBI
6	Boyd KT and Myers PT: Meniscus preservation; rationale, repair techniques and results. Knee. 10:1–11. 2003. View Article : Google Scholar : PubMed/NCBI
7	Cook JL: The current status of treatment for large meniscal defects. Clin Orthop Relat Res. 88–95. 2005. View Article : Google Scholar : PubMed/NCBI
8	Setton LA, Guilak F, Hsu EW and Vail TP: Biomechanical factors in tissue engineered meniscal repair. Clin Orthop Relat Res (Suppl). S254–S272. 1999. View Article : Google Scholar
9	Fraser JK, Wulur I, Alfonso Z and Hedrick MH: Fat tissue: An underappreciated source of stem cells for biotechnology. Trends Biotechnol. 24:150–154. 2006. View Article : Google Scholar : PubMed/NCBI
10	Qi Y, Feng G, Huang Z and Yan W: The application of super paramagnetic iron oxide-labeled mesenchymal stem cells in cell-based therapy. Mol Biol Rep. 40:2733–2740. 2013. View Article : Google Scholar : PubMed/NCBI
11	Saldanha KJ, Doan RP, Ainslie KM, Desai TA and Majumdar S: Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering. Magn Reson Imaging. 29:40–49. 2011. View Article : Google Scholar : PubMed/NCBI
12	Hill JM, Dick AJ, Raman VK, Thompson RB, Yu ZX, Hinds KA, Pessanha BS, Guttman MA, Varney TR, Martin BJ, et al: Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation. 108:1009–1014. 2003. View Article : Google Scholar : PubMed/NCBI
13	An C, Cheng Y, Yuan Q and Li J: IGF-1 and BMP-2 induces differentiation of adipose-derived mesenchymal stem cells into chondrocytes-like cells. Ann Biomed Eng. 38:1647–1654. 2010. View Article : Google Scholar : PubMed/NCBI
14	Hsiao JK, Tai MF, Chu HH, Chen ST, Li H, Lai DM, Hsieh ST, Wang JL and Liu HM: Magnetic nanoparticle labeling of mesenchymal stem cells without transfection agent: Cellular behavior and capability of detection with clinical 1.5 T magnetic resonance at the single cell level. Magn Reson Med. 58:717–724. 2007. View Article : Google Scholar : PubMed/NCBI
15	Yang CY, Hsiao JK, Tai MF, Chen ST, Cheng HY, Wang JL and Liu HM: Direct labeling of hMSC with SPIO: The long-term influence on toxicity, chondrogenic differentiation capacity, and intracellular distribution. Mol Imaging Biol. 13:443–451. 2011. View Article : Google Scholar : PubMed/NCBI
16	Mankin HJ, Dorfman H, Lippiello L and Zarins A: Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 53:523–537. 1971.PubMed/NCBI
17	Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D and van den Berg WB: Osteoarthritis cartilage histopathology: Grading and staging. Osteoarthritis Cartilage. 14:13–29. 2006. View Article : Google Scholar : PubMed/NCBI
18	Henning TD, Sutton EJ, Kim A, Golovko D, Horvai A, Ackerman L, Sennino B, McDonald D, Lotz J and Daldrup-Link HE: The influence of ferucarbotran on the chondrogenesis of human mesenchymal stem cells. Contrast Media Mol Imaging. 4:165–173. 2009. View Article : Google Scholar : PubMed/NCBI
19	Arbab AS, Bashaw LA, Miller BR, Jordan EK, Lewis BK, Kalish H and Frank JA: Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology. 229:838–846. 2003. View Article : Google Scholar : PubMed/NCBI
20	Mailänder V, Lorenz MR, Holzapfel V, Musyanovych A, Fuchs K, Wiesneth M, Walther P, Landfester K and Schrezenmeier H: Carboxylated superparamagnetic iron oxide particles label cells intracellularly without transfection agents. Mol Imaging Biol. 10:138–146. 2008. View Article : Google Scholar : PubMed/NCBI
21	Metz S, Bonaterra G, Rudelius M, Settles M, Rummeny EJ and Daldrup-Link HE: Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro. Eur Radiol. 14:1851–1858. 2004. View Article : Google Scholar : PubMed/NCBI
22	Qi Y, Zhao T, Xu K, Dai T and Yan W: The restoration of full-thickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model. Mol Biol Rep. 39:1231–1237. 2012. View Article : Google Scholar : PubMed/NCBI
23	Chen FH and Tuan RS: Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther. 10:2232008. View Article : Google Scholar : PubMed/NCBI
24	Kern S, Eichler H, Stoeve J, Klüter H and Bieback K: Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 24:1294–1301. 2006. View Article : Google Scholar : PubMed/NCBI
25	Horie M, Sekiya I, Muneta T, Ichinose S, Matsumoto K, Saito H, Murakami T and Kobayashi E: Intra-articular injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect. Stem Cells. 27:878–887. 2009. View Article : Google Scholar : PubMed/NCBI
26	Murphy JM, Fink DJ, Hunziker EB and Barry FP: Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 48:3464–3474. 2003. View Article : Google Scholar : PubMed/NCBI
27	Ruiz-Ibán MA, Díaz-Heredia J, García-Gómez I, Gonzalez-Lizán F, Elías-Martín E and Abraira V: The effect of the addition of adipose-derived mesenchymal stem cells to a meniscal repair in the avascular zone: An experimental study in rabbits. Arthroscopy. 27:1688–1696. 2011. View Article : Google Scholar : PubMed/NCBI
28	Qi Y, Feng G and Yan W: Mesenchymal stem cell-based treatment for cartilage defects in osteoarthritis. Mol Biol Rep. 39:5683–5689. 2012. View Article : Google Scholar : PubMed/NCBI
29	Uccelli A, Pistoia V and Moretta L: Mesenchymal stem cells: A new strategy for immunosuppression? Trends Immunol. 28:219–226. 2007. View Article : Google Scholar : PubMed/NCBI
30	Chen X, Armstrong MA and Li G: Mesenchymal stem cells in immunoregulation. Immunol Cell Biol. 84:413–421. 2006. View Article : Google Scholar : PubMed/NCBI
31	Caplan AI and Dennis JE: Mesenchymal stem cells as trophic mediators. J Cell Biochem. 98:1076–1084. 2006. View Article : Google Scholar : PubMed/NCBI
32	Koelling S and Miosge N: Stem cell therapy for cartilage regeneration in osteoarthritis. Expert Opin Biol Ther. 9:1399–1405. 2009. View Article : Google Scholar : PubMed/NCBI
33	Bulte JW and Kraitchman DL: Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed. 17:484–499. 2004. View Article : Google Scholar : PubMed/NCBI