화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.104, 381-389, December, 2021
DOI10.1016/j.jiec.2021.08.032  Export Citation
Delivery of extracellular matrix-enriched stem cells encapsulated with enzyme-free pH-sensitive polymer for enhancing therapeutic angiogenesis
Jihun Song1, Gun-Jae Jeong2, Tae-Jin Lee1, 3, Sung-Won Kim1, Yu-Jin Kim1, and Suk Ho Bhang1, †
  • 1School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, South Korea
  • 2School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
  • 3Department of Bio-Health Convergence, Kangwon National University, Chuncheon 24341, South Korea
E-mail:
At clinical transplantation of human adipose derived stem cells (hADSCs), a proteolytic enzyme treatment for harvesting hADSCs must be used but usually causes the disruption of extracellular matrices (ECMs) interconnection. As ECMs-poor hADSCs partially receive the cellular signals, hADSCs deactivated or undergo cell death. Herein, we have proposed a method for delivering ECMs-enriched hADSCs encapsulated with a new polymer for transplanting into ischemic wound sites to enhance the therapeutic angiogenic efficacy. Enzyme free pH-sensitive polymer (EFP) was synthesized and coated on tissue culture plate for hADSCs culture. When the hADSCs were cultured on EFP-coated surfaces, they were easily detached with pH 6.0 buffer solution and dissolved EFP wrapped hADSCs with more ECMs for 48 h. When ECMs enriched-hADSCs were re-adhered, the cells secreted more angiogenic factors under serum free and hypoxic cell culture condition. When injecting ECMs-enriched hADSCs to mouse hindlimb ischemia models, the blood perfusion and blood vessel regeneration rate were significantly higher. Our method for delivering ECMs-enriched stem cells using EFP significantly improved the therapeutic angiogenesis with hADSCs compared to proteolytic enzymatic application.
Keywords:Angiogenesis;Extracellular matrix;Stem cell therapy
  1. Tang YL, Zhao Q, Qin X, Shen L, Cheng L, Ge J, Phillips MI, Ann. Thor. Surg., 80, 229 (2005)
  2. Wu Y, Zhao RC, Tredget EE, Stem Cells, 28, 905 (2010)
  3. Ankrum J, Karp JM, Trends Mol. Med., 16, 203 (2010)
  4. Menasche P, Thromb. Haemost., 94, 697 (2005)
  5. Squillaro T, Peluso G, Galderisi U, Cell Transplant., 25, 829 (2016)
  6. Trounson A, McDonald C, Cell Stem Cell, 17, 11 (2015)
  7. Deuse T, Peter C, Fedak PW, Doyle T, Reichenspurner H, Zimmermann WH, Eschenhagen T, Stein W, Wu JC, Robbins RC, Circulation, 120, S247 (2009)
  8. Kim MJ, Kim HS, Gao X, Ryu JH, Yang YS, Kwon IC, Toberts TM, Kim SH, J. Ind. Eng. Chem., 99, 196 (2021)
  9. Bhang SH, Cho SW, La WG, Lee TJ, Yang HS, Sun AY, Baek SH, Rhie JW, Kim BS, Biomaterials, 32, 2734 (2011)
  10. Hu X, Yu SP, Fraser JL, Lu Z, Ogle ME, Wang JA, Wei L, J. Thorac. Cardiovasc. Surg., 135, 799 (2008)
  11. Park H, Temenoff JS, Tabata Y, Caplan AI, Mikos AG, Biomaterials, 28, 3217 (2007)
  12. Jo HJ, Shit A, Jhon HS, Park SY, J. Ind. Eng. Chem., 89, 485 (2020)
  13. Kim SG, Robby AI, Lee BC, Lee GB, Park SY, J. Ind. Eng. Chem., 99, 98 (2021)
  14. Anderson SB, Lin CC, Kuntzler DV, Anseth KS, Biomaterials, 32, 3564 (2011)
  15. de Vos P, Lazarjani HA, Poncelet D, Faas MM, Adv. Drug Deliv. Rev., 67, 15 (2014)
  16. Yang J, Yang Y, Kawazoe N Chen G, Biomaterials, 197, 317 (2019)
  17. He N, Xu Y, Du W, Qi X, Liang L, Wang Y, Feng G, Fan Y, Han Z, Kong D, Sci. Rep., 5, 1 (2015)
  18. Krishna OD, Jha AK, Jia X, Kiick KL, Biomaterials, 32, 6412 (2011)
  19. Hashimoto J, Kariya Y, Miyazaki K, Stem Cells, 24, 2346 (2006)
  20. Tohamy KM, Mabrouk M, Soliman IE, Beherei HH, Aboelnasr MA, Int. J. Biol. Macromol., 112, 448 (2018)
  21. Brun-Graeppi AKAS, Richard C, Bessodes M, Scherman D, Merten OW, Prog. Polym. Sci, 35, 1311 (2010)
  22. Guillaume-Gentil O, Semenov OV, Zisch AH, Zimmermann R, Voros J, Ehrbar M, Biomaterials, 32, 4376 (2011)
  23. Krishnamoorthy M, Hakobyan S, Ramstedt M, Gautrot JE, Chem. Rev., 114(21), 10976 (2014)
  24. Elloumi-Hannachi I, Yamato M, Okano T, J. Intern. Med., 267, 54 (2010)
  25. Inaba R, Khademhosseini A, Suzuki H, Fukuda J, Biomaterials, 30, 3573 (2009)
  26. Seto Y, Inaba R, Okuyama T, Sassa F, Suzuki H, Fukuda J, Biomaterials, 31, 2209 (2010)
  27. Guillaume-Gentil O, Akiyama Y, Schuler M, Tang C, Textor M, Yamato M, Okano T, Voros J, Adv. Mater., 20(3), 560 (2008)
  28. Sponchioni M, Palmiero UC, Moscatelli D, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 102, 589 (2019)
  29. Zhao C, Nie S, Tang M, Sun S, Prog. Polym. Sci, 36, 1499 (2011)
  30. Du JZ, Du XJ, Mao CQ, Wang J, J. Am. Chem. Soc., 133(44), 17560 (2011)
  31. Cheung CY, Murthy N, Stayton PS, Hoffman AS, Bioconjug. Chem., 12, 906 (2001)
  32. Chang HH, Cheng NC, Li YCE, Wang JH, Young TH, J. Taiwan Inst. Chem. Eng., 11, 34 (2020)
  33. Potineni A, Lynn DM, Langer R, Amiji MM, J. Control. Release, 86, 223 (2003)
  34. Min KH, Kim JH, Bae SM, Shin H, Kim MS, Park S, Lee H, Park RW, Kim IS, Kim K, J. Control. Release, 144, 259 (2010)
  35. Lee JSJ, Kim SJ, Choi JS, Eom MR, Shin HS, Kwon SK, J. Ind. Eng. Chem., 91, 296 (2020)
  36. Niiyama H, Huang NF, Rollins MD, Cooke JP, J. Visual. Exp.: JoVE (2009).
  37. Burridge K, Fath K, Kelly T, Nuckolls G, Turner C, Annu. Rev. Cell Biol., 4, 487 (1988)
  38. Floros KV, Thomadaki H, Florou D, Talieri M, Scorilas A, Ann. N. Y. Acad. Sci., 1090, 89 (2006)
  39. Nunan R, Harding KG, Martin P, Disease Models Mechan., 7, 1205 (2014)
  40. Duan H, Cheng L, Sun X, Wu Y, Hu L, Wang J, Zhao H, Lu G, Thromb. Haemost., 96, 807 (2006)
  41. Peled A, Grabovsky V, Habler L, Sandbank J, Arenzana-Seisdedos F, Petit I, Ben-Hur H, Lapidot T, Alon R, J. Clin. Investig., 104, 1199 (1999)
  42. Lertkiatmongkol P, Liao D, Mei H, Hu Y, Newman PJ, Curr. Opin. Hematol., 23, 253 (2016)
  43. Pusztaszeri MP, Seelentag W, Bosman FT, J. Histochem. Cytochem., 54, 385 (2006)
  44. Guo DC, Papke CL, Tran-Fadulu V, Regalado ES, Avidan N, Johnson RJ, Kim DH, Pannu H, Willing MC, Sparks E, Am. J. Human Genet., 84, 617 (2009)
  45. Antebi B, Zhang Z, Wang Y, Lu Z, Chen XD, Ling J, Tissue Eng. Part C, 21, 171 (2015)
  46. Rakian R, Block TJ, Johnson SM, Marinkovic M, Wu J, Dai Q, Dean DD, Chen XD, Stem Cell Res. Ther., 6, 1 (2015)
  47. Watt FM, Huck WT, Nat. Rev. Mol. Cell Biol., 14, 467 (2013)
  48. Taddei M, Giannoni E, Fiaschi T, Chiarugi P, J. Pathol., 226, 380 (2012)
  49. Heng BC, Cowan CM, Basu S, Biological procedures online, 11, 161 (2009).
  50. Gilbert TW, Sellaro TL, Badylak SF, Biomaterials, 27, 3675 (2006)