OJRM  Vol.2 No.4 , December 2013
Evaluation of in vivo migration of chondrocytes from tissue-engineered cartilage that was subcutaneously transplanted in mouse model
ABSTRACT

For regenerative medicine, clarification of in vivo migration of transplanted cells is an important task to secure the safety of transplanted tissue. We had prepared tissue-engineered cartilage consisting of cultured chondrocytes with collagen hydrogel and a biodegradable porous polymer, and we clinically applied it for treatment of craniofacial anomaly. To verify the safety of this tissue-engineered cartilage, we had syngenically transplanted the tissue-engineered cartilage using chondrocytes harvested from EGFP-transgenic mice into subcutaneous pocket of wild type mice, and investigated localizations of transplanted chondrocytes in various organs including cerebrum, lung, liver, spleen, kidney, auricle, gastrocnemius, and femur. After 8 to 24 weeks of the transplantation, accumulation of cartilaginous matrices was observed in tissue-engineered cartilage, while EGFP-positive transplanted chondrocytes were localized in this area. Otherwise, no EGFP was immunohistochemically detected in each organ, suggesting that subcutaneously-transplanted chondrocytes do not migrate to other organs through the circulation. In cartilage tissue engineering using cultured chondrocytes, risk for migration and circulation of transplanted cells seemed negligible, and that ectopic growth of the cells was unlikely to occur, showing that this is safe technique with regard to the in vivo migration of transplanted cells.


Cite this paper
Matsuyama, M. , Fujihara, Y. , Inaki, R. , Nishizawa, S. , Nagata, S. , Takato, T. and Hoshi, K. (2013) Evaluation of in vivo migration of chondrocytes from tissue-engineered cartilage that was subcutaneously transplanted in mouse model. Open Journal of Regenerative Medicine, 2, 93-98. doi: 10.4236/ojrm.2013.24013.
References
[1]   Brittberg, M., Lindahl, A., Nilsson A., Ohlsson, C., Isaksson, O. and Peterson, L. (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. The New England Journal of Medicine, 331, 889-895. http://dx.doi.org/10.1056/NEJM199410063311401

[2]   Ochi, M., Uchio, Y., Kawasaki, K., Wakitani, S. and Iwasa, J. (2002) Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee. Journal of Bone & Joint Surgery, 84, 571-578. http://dx.doi.org/10.1302/0301-620X.84B4.11947

[3]   Hoshi, K., Fujihara, Y., Asawa, Y., Nishizawa, S., Kanazawa, S., Sakamoto, T., Watanabe, M., Ogasawara, T., Saijo, H., Mori, Y. and Takato, T. (2013) Recent trends of cartilage regenerative medicine and its application to the oral and maxillofacial surgery. Oral Science International, 15, 15-19.

[4]   Yamaoka, H., Tanaka, Y., Nishizawa, S., Asawa, Y., Takato, T. and Hoshi, K. (2010) The application of atelocollagen gel in combination with porous scaffolds for cartilage tissue engineering and its suitable condtions. Journal of Biomedical Materials Research Part A, 93, 123-132. http://dx.doi.org/10.1002/jbm.a.32509

[5]   Abedin, M., Tintut, Y. and Demer, L.L. (2004) Mesenchymal stem cells and the artery wall. Circulation Research, 95, 671-676. http://dx.doi.org/10.1161/01.RES.0000143421.27684.12

[6]   Asawa, Y., Sakamoto, T., Komura, M., Watanabe, M., Nishizawa, S., Takazawa, Y., Takato, T. and Hoshi, K. (2012) Early stage foreign body reaction against biodegradable polymer scaffolds affects tissue regeneration during the autologous transplantation of tissue-engineered cartilage in the canine model. Cell Transplant, 21, 1431-1442. http://dx.doi.org/10.3727/096368912X640574

[7]   Fujihara, Y., Takato, T. and Hoshi, K. (2010) Immunological response to tissue-engineered cartilage derived from auricular chondrocytes and a PLLA scaffold in transgenic mice. Biomaterials, 31, 1227-1234. http://dx.doi.org/10.1016/j.biomaterials.2009.10.053

[8]   Takahashi, T., Ogasawara, T., Kishimoto, J., Liu, G., Asato, H., Nakatsuka, T., Uchinuma, E., Nakamura, K., Kawaguchi, H., Chung, U.I., Takato, T. and Hoshi, K. (2005) Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human auricular chondrocytes. Cell Transplant, 14, 683-693. http://dx.doi.org/10.3727/000000005783982675

[9]   Holleran, J.L., Miller, C.J., Edgehouse, N.L., Pretlow, T.P. and Culp, L.A. (2002) Differential experimental micrometastasis to lung, liver, and bone with lacZ-tagged CWR22R prostate carcinoma cells. Clinical & Experimental Metastasis, 19, 17-24. http://dx.doi.org/10.1023/A:1013833111207

[10]   Nguyen, D.X., Bos, P.D. and Massagué, J. (2009) Metastasis: From dissemination to organ-specific colonization. Nature Reviews Cancer, 9, 274-284. http://dx.doi.org/10.1038/nrc2622

[11]   Gao, J.L., Ji, X., He, T.C., Zhang, Q., He, K., Zhao, Y., Chen, S.H. and Lv, G.Y. (2013) Tetrandrine Suppresses Cancer Angiogenesis and Metastasis in 4T1 Tumor Bearing Mice. Evidence-Based Complementary and Alternative Medicine, 2013, 265061. http://dx.doi.org/10.1155/2013/265061

[12]   Matsumoto, Y., Zhang, Q., Akita, K., Nakada, H., Hamamura, K., Tsuchida, A., Okajima, T., Furukawa, K., Urano, T. and Furukawa, K. (2013) Trimeric Tn antigen on Syndecan-1 produced by ppGalNAc-T13 enhances cancer metastasis via a complex formation with integrin α5β1 and matrix metalloproteinase 9. Journal of Biological Chemistry, 288, 24264-24276. http://dx.doi.org/10.1074/jbc.M113.455006

[13]   Chien, M.H., Lee, L.M., Hsiao, M., Wei, L.H., Chen, C,H., Lai, T.C., Hua, K.T., Chen, M.W., Sun, C.M. and Kuo, M.L. (2013) Inhibition of metastatic potential in breast carcinoma in vivo and in vitro through targeting VEGFRs and FGFRs. Evidence-Based Complementary and Alternative Medicine, 2013, 718380. http://dx.doi.org/10.1155/2013/718380

[14]   Huang, Q.B., Ma, X., Zhang, X., Liu, S.W., Ai, Q., Shi, T.P., Zhang, Y., Gao, Y., Fan, Y., Ni, D., Wang, B.J., Li, H.Z. and Zheng, T. (2013) Down-regulated miR-30a in clear cell renal cell carcinoma correlated with tumor hematogenous metastasis by targeting angiogenesis-specific DLL4. PLoS One, 8, e67294. http://dx.doi.org/10.1371/journal.pone.0067294

[15]   Yoshimura, T., Howard, O.M., Ito, T., Kuwabara, M., Matsukawa, A., Chen, K., Liu, Y., Liu, M., Oppenheim, J.J. and Wang, J.M. (2013) Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells. PLoS One, 8, e58791. http://dx.doi.org/10.1371/journal.pone.0058791

[16]   Zhao, X., Pang, L., Qian, Y., Wang, Q., Li, Y., Wu, M., Ouyang, Z., Gao, Z. and Qiu, L. (2013) An animal model of buccal mucosa cancer and cervical lymph node metastasis induced by U14 squamous cell carcinoma cells. Experimental and Therapeutic Medicine, 5, 1083-1088. http://dx.doi.org/10.3892/etm.2013.938

[17]   Jeong, J., Lee, K.S., Choi, Y.K., Oh, Y.J. and Lee, H.D. (2011) Preventive effects of zoledronic acid on bone metastasis in mice injected with human breast cancer cells. Journal of Korean Medical Science, 26, 1569-1575. http://dx.doi.org/10.3346/jkms.2011.26.12.1569

[18]   Li, G.C., Ye, Q.H., Dong, Q.Z., Ren, N., Jia, H.L. and Qin, L.X. (2012) TGF beta1 and related-Smads contribute to pulmonary metastasis of hepatocellular carcinoma in mice model. Journal of Experimental & Clinical Cancer Research, 14, 93. http://dx.doi.org/10.1186/1756-9966-31-93

[19]   Asawa, Y., Ogasawara, T., Takahashi, T., Yamaoka, H., Nishizawa, S., Matsudaira, K., Mori, Y., Takato, T. and Hoshi, K. (2009) Aptitude of auricular and nasoseptal chondrocytes cultured under a monolayer or three-dimensional condition for cartilage tissue engineering. Tissue Engineering Part A, 15, 1109-1118. http://dx.doi.org/10.1089/ten.tea.2007.0218

[20]   Yamaoka, H., Nishizawa, S., Asawa, Y., Fujihara, Y., Ogasawara, T., Yamaoka, K., Nagata, S., Takato, T. and Hoshi, K. (2010) Involvement of fibroblast growth factor 18 in dedifferentiation of cultured human chondrocytes. Cell Proliferation, 43, 67-76. http://dx.doi.org/10.1111/j.1365-2184.2009.00655.x

[21]   Liu, G., Kawaguchi, H., Ogasawara, T., Asawa, Y., Kishimoto, J., Takahashi, T., Chung, U.I., Yamaoka, H., Asato, H., Naka-mura, K., Takato, T. and Hoshi, K. (2007) Optimal combination of soluble factors for tissue engineering of permanent cartilage from cultured human chondrocytes. Journal of Biological Chemistry, 282, 20407-20415. http://dx.doi.org/10.1074/jbc.M608383200

[22]   Menendez, S., Camus, S., Herreria, A., Paramonov, I., Morera, L.B., Collado, M., Pekarik, V., Maceda, I., Edel, M., Consiglio, A., Sanchez, A., Li, H., Serrano, M. and Belmonte, J.C. (2012) Increased dosage of tumor suppressors limits the tumorigenicity of iPS cells without affecting their pluripotency. Aging Cell, 11, 41-50. http://dx.doi.org/10.1111/j.1474-9726.2011.00754.x

[23]   Chen, T., Yuan, D., Wei, B., Jiang, J., Kang, J., Ling, K., Gu, Y., Li, J., Xiao, L. and Pei. G. (2010) E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation. Stem Cells, 28, 1315-1325. http://dx.doi.org/10.1002/stem.456

[24]   Yamaoka, H., Asato, H., Ogasawara, T., Nishizawa, S., Takahashi, T., Nakatsuka, T., Koshima, I., Nakamura, K., Kawaguchi, H., Chung, U.I., Takato, T. and Hoshi, K. (2006) Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials. Journal of Biomedical Materials Research Part A, 78, 1-11. http://dx.doi.org/10.1002/jbm.a.30655

[25]   Barbash, I.M., Chouraqui, P., Baron, J., Feinberg, M.S., Etzion, S., Tessone, A., Miller, L., Guetta, E., Zipori, D., Kedes, L.H., Kloner, R.A. and Leor, J. (2003) Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation, 108, 863-868. http://dx.doi.org/10.1161/01.CIR.0000084828.50310.6A

[26]   Liu, G., Iwata, K., Ogasawara, T., Watanabe, J., Fukazawa, K., Ishihara, K., Asawa Y., Fujihara, Y., Chung, U.L., Moro, T., Takatori, Y., Takato, T., Nakamura, K., Kawaguchi, H. and Hoshi, K. (2010) Selection of highly osteogenic and chondrogenic cells from bone marrow stromal cells in biocompatible polymer-coated plates. Journal of Biomedical Materials Research Part A, 92, 1273-1282. http://dx.doi.org/10.1002/jbm.a.32460

[27]   Terada, N., Hamazaki, T., Oka, M., Hoki, M., Mastalerz, D.M., Nakano, Y., Meyer, E.M., Morel, L., Petersen, B.E. and Scott, E.W. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature, 416, 542-545. http://dx.doi.org/10.1038/nature730

 
 
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