Abstract
Biodegradable porous microspheres, which were initially used as supports for cell growth, are known to have the advantages of maintaining a differentiated cell phenotype and allowing for cell expansion owing to their large surface area. The use of porous microspheres ensures good retention of engrafted cells as platforms for cell delivery. In this study, injectable and porous poly(D, L-lactic-co-glycolic acid) (PLGA) microspheres were fabricated using a microfluidic system. These microspheres had a relatively uniform size and a porous and interconnected internal structure. The prepared PLGA microspheres were used as stem cell carriers for therapy. Here, we demonstrated the feasibility of mesenchymal stem cell (MSC)-loaded microspheres as cell therapy agents for liver damage. The results obtained from a chemically induced liver damage model showed that MSC-loaded microspheres effectively promoted liver recovery. These findings clearly show the feasibility of using injectable microspheres for the therapy and regeneration of tissues.
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N. Jaiswal, S. E. Haynesworth, A. I. Caplan, and S. P. Bruder, J. Cellular Biochemistry, 64, 295 (1997).
S. P. Bruder and B. S. Fox, Clin. Orthop. Relat. Res., 367 Suppl, S68 (1999).
C. W. Patrick, Anat. Rec., 263, 361 (2001).
C. W. Patrick, Surg. Oncol., 19, 302 (2000).
L. C. Amado, A. P. Saliaris, K. H. Schuleri, M. St. John, J.-S. Xie, S. Cattaneo, D. J. Durand, T. Fitton, J. Q. Kuang, G. Stewart, S. Lehrke, W. W. Baumgartner, B. J. Martin, A. W. Heldman, and J. M. Hare, Proc. Natl. Acad. Sci., U.S.A., 102, 11474 (2005).
A. W. Heldman and J. M. Hare, J. Mol. Cell. Cardiol., 44, 473 (2008).
D. Luger, M. J. Lipinski, P. C. Westman, D. K. Glover, J. Dimastromatteo, J. C. Frias, M. T. Albelda, S. Sikora, A. Kharazi, G. Vertelov, R. Waksman, and S. E. Epstein, Circ. Res., 120, 1598 (2017).
K. D. Lee, T. K. Kuo, J. Whang-Peng, Y. F. Chung, C. T. Lin, S. H. Chou, J. R. Chen, Y. P. Chen, and O. K. Lee, Hepatology, 40, 1275 (2004).
R. E. Schwartz, M. Reyes, L. Koodie, Y. Jiang, M. Blackstad, T. Lund, T. Lenvik, S. Johnson, W. S. Hu, and C. M. Verfaillie, J. Clin. Invest., 109, 1291 (2002).
D. Baksh, L. Song, and R. S. Tuan, J. Cell. Mol. Med., 8, 301 (2004).
W. Li, S. N. Liu, D. D. Luo, L. Zhao, L. L. Zeng, S. L. Zhang, and S. L. Li, World J. Gastroenterol., 12, 4866 (2006).
Y. Zhan, Y. Wang, L. Wei, H. Chen, X. Cong, R. Fei, Y. Gao, and F. Liu, Transplant. Proceedings, 38, 3082 (2006).
D. C. Zhao, J. X. Lei, R. Chen, W. H. Yu, X. M. Zhang, S. N. Li, and P. Xiang, World J. Gastroenterol., 11, 3431 (2005).
S. Berardis, P. D. Sattwika, M. Najimi, and E. M. Sokal, World J. Gastroenterol., 21, 742 (2015).
J. V. Terrovitis, R. R. Smith, and E. Marbán, Circ. Res., 106, 479 (2010).
K. Cheng, T. S. Li, K. Malliaras, D. R. Davis, Y. Zhang, and E. Marbán, Circ. Res., 106, 1570 (2010).
K. M. Dupont, K. Sharma, H. Y. Stevens, J. D. Boerckel, A. J. Garcia, and R. E. Guldberg, Proc. Natl. Acad. Sci., 107, 3305 (2010).
S. Redenti, W. L. Neeley, S. Rompani, S. Saigal, J. Yang, H. Klassen, R. Langer, and M. J. Young, Biomaterials, 30, 3405 (2009).
M. Habib, K. Shapira-Schweitzer, O. Caspi, A. Gepstein, G. Arbel, D. Aronson, D. Seliktar, and L. Gepstein, Biomaterials, 32, 7514 (2011).
Z. Ye, Y. Zhou, H. Cai, and W. Tan, Adv. Drug Deliv. Rev., 63, 688 (2010).
Y. Miyagi, F. Zeng, X.-P. Huang, W. D. Foltz, J. Wu, A. Mihic, T. M. Yau, R. D. Weisel, and R.-K. Li, Biomaterials, 31, 7684 (2010).
H. W. Ooi, S. Hafeez, C. A. van Blitterswijk, L. Moroni, and M. B. Baker, Mater. Horizons, 4, 1020 (2017).
J. Demol, D. Lambrechts, L. Geris, J. Schrooten, and H. van Oosterwyck, Biomaterials, 32, 107 (2011).
Y. Hong, Y. Gong, C. Gao, and J. Shen, J. Biomed. Mater. Res. Part A, 85, 628 (2008).
K. M. Park, S. Y. Lee, Y. K. Joung, J. S. Na, M. C. Lee, and K. D. Park, Acta Biomater., 5, 1956 (2009).
S. Redenti, S. Tao, J. Yang, P. Gu, H. Klassen, S. Saigal, T. Desai, and M. J. Young, J. Ocular Biology, Diseases, and Informatics, 1, 19 (2008).
W. L. Neeley, S. Redenti, H. Klassen, S. Tao, T. Desai, M. J. Young, and R. Langer, Biomaterials, 29, 418 (2008).
S. Tao, C. Young, S. Redenti, Y. Zhang, H. Klassen, T. Desai, and M. J. Young, Lab Chip, 7, 695 (2007).
M. Tomita, E. Lavik, H. Klassen, T. Zahir, R. Langer, and M. J. Young, Stem Cells, 23, 1579 (2005).
S. J. Hollister, Nat. Mater., 4, 518 (2005).
R. G. Flemming, C. J. Murphy, G. A. Abrams, S. L. Goodman, and P. F. Nealey, Biomaterials, 20, 573 (1999).
T. J. Webster, C. Ergun, R. H. Doremus, R. W. Siegel, and R. Bizios, Biomed. Mater., 2, 124 (2007).
A. Tampieri, G. Celotti, S. Sprio, A. Delcogliano, and S. Franzese, Biomaterials, 22, 1365 (2001).
S.-W. Choi, Y.-C. Yeh, Y. Zhang, H.-W. Sung, and Y. Xia, Small, 6, 1492 (2010).
J. H. Ryu, S. S. Kim, S. W. Cho, C. Y. Choi, and B. S. Kim, J. Biomed. Mater. Res. A, 71, 128 (2004).
S.-W. Kang and Y. H. Bae, Biomaterials, 30, 4227 (2009).
Y.-J. Chang, J.-W. Liu, P.-C. Lin, L.-Y. Sun, C.-W. Peng, G.-H. Luo, T.-M. Chen, R.-P. Lee, S.-Z. Lin, H.-J. Harn, and T.-W. Chiou, Life Sci., 85, 517 (2009).
D. C. Zhao, J. X. Lei, R. Chen, W. H. Yu, X. M. Zhang, S. N. Li, and P. Xiang, World J. Gastroenterol., 11, 3431 (2005).
M. T. Abdel Aziz, H. M. Atta, S. Mahfouz, H. H. Fouad, N. K. Roshdy, H. H. Ahmed, L. A. Rashed, D. Sabry, A. A. Hassouna, and N. M. Hasan, Clin. Biochem., 40, 893 (2007).
T. K Kim, J. J. Yoon, D. S. Lee, and T. G. Park, Biomaterials, 27, 152 (2006).
P. Mullen, Methods Mol. Med., 88, 287 (2004).
M. Massumi, M. Abasi, H. Babaloo, P. Terraf, M. Safi, M. Saeed, J. Barzin, M. Zandi, and M. Soleimani, Tissue Eng. Part A, 18, 609 (2012).
S. W. Kang, S. W. Seo, C. Y. Choi, and B. S. Kim, Tissue Engineering Part C: Methods, 14, 25 (2008).
S. W. Kang, W. G. La, and B. S. Kim, J. Biomaterials Sci. Polym. Ed., 20, 399 (2009).
S. Shintani, T. Murohara, H. Ikeda, T. Ueno, K. Sasaki, J. Duan, and T. Imaizumi, Circulation, 103, 897 (2001).
D. Orlic, J. Kajstura, S. Chimenti, I. Jakoniuk, S. M. Anderson, B. Li, J. Pickel, R. McKay, B. Nadal-Ginard, D. M. Bodine, A. Leri, and P. Anversa, Nature, 410, 701 (2001).
S. W. Cho, S. J. Gwak, S. W. Kang, S. H. Bhang, K. W. Song, Y. S. Yang, C. Y. Choi, and B.-S. Kim, Tissue Eng., 12, 1651 (2006).
P. Akhyari, H. Kamiya, A. Haverich, M. Karck, A. Lichtenberg, Eur. J. Cardio-Thoracic Surg., 34, 229 (2008).
C. V. C. Bouten, P. Y. W. Dankers, A. Driessen-Mol, S. Pedron, A. M. A. Brizard, and F. P. T. Baaijens, Adv. Drug Deliv. Rev., 63, 221 (2011).
S. Battista, D. Guarnieri, C. Borselli, S. Zeppetelli, A. Borzacchiello, L. Mayol, D. Gerbasio, D. R. Keene, L. Ambrosio, and P. A. Netti, Biomaterials, 26, 6194 (2005).
C.-C. Huang, H.-J. Wei, Y.-C. Yeh, J.-J. Wang, W.-W. Lin, T.-Y. Lee, S.-M. Hwang, S.-W. Choi, Y. Xia, Y. Chang, and H.-W. Sung, Biomaterials, 33, 4069 (2012).
E. Tsolaki and E. Yannaki, World J. Gastroenterol., 21, 12334 (2015).
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Park, MJ., Choi, M., Kim, M. et al. Injectable and Cryopreservable MSC-Loaded PLGA Microspheres for Recovery from Chemically Induced Liver Damage. Macromol. Res. 28, 1017–1025 (2020). https://doi.org/10.1007/s13233-020-8139-4
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DOI: https://doi.org/10.1007/s13233-020-8139-4