Fortifying the angiogenic efficacy of adipose derived stem cell spheroids using spheroid compaction

Gwang-Bum Im; Sung-Won Kim; Suk Ho Bhang

Journal of Industrial and Engineering Chemistry, Vol.93, 228-236, January, 2021

DOI10.1016/j.jiec.2020.09.027 Export Citation

Fortifying the angiogenic efficacy of adipose derived stem cell spheroids using spheroid compaction

Gwang-Bum Im, Sung-Won Kim, and Suk Ho Bhang^†

School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea

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Transplantation of stem cell spheroids to ischemic tissues has been suggested as an effective method for treating ischemic disease, but its therapeutic efficacy varies according to the preparation methods for spheroids. We hypothesized that increasing cell compaction while preparing spheroids could improve the angiogenic efficacy of spheroids. Optimized human adipose derived stem cell (hADSC) spheroids were shown to upregulate cell adhesion molecule, and angiogenic paracrine factors expression with downregulated senescence and apoptotic markers expression. We noted that the low seeding density (1 × 104 cells (10KS)) had a far lower probability of forming spheroids than higher seeding densities (3 × 104 cells (30KS) and 1 × 105 cells (100KS)). The 30KS spheroids demonstrated higher cell density and expression levels of the angiogenic paracrine factor expression compared to those of 100 KS spheroids. 30KS spheroids with additional incubation (A30KS) showed significantly increased angiogenic paracrine factors and cell adhesion molecule expressions with decreased senescence expression compared to those in 30KS spheroids. Transplanting A30KS spheroids showed significantly enhanced therapeutic angiogenesis in mouse hindlimb ischemia model compared to conventional spheroid transplantation. This study successfully defined a set of novel criteria for spheroid culture, which may contribute to future stem cell therapies.

Keywords:Adipose derived stem cells;Angiogenesis;Cell density;Compaction;Spheroids

[References]

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Joshi P, Lee MY, Biosensors, 5(4), 768 (2015)
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[Referenced By]

[1] Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, et al., Lancet, 360, 427 (2002)

[2] Bhang SH, Cho SW, La WG, Lee TJ, Yang HS, Sun AY, Baek SH, Rhie JW, Kim BS, Biomaterials, 32, 2734 (2011)

[3] Murphy KC, Whitehead J, Zhou D, Ho SS, Leach JK, Acta Biomater., 64, 176 (2017)

[4] Sun Y, Wang Y, Zhou L, Zou Y, Huang G, Gao G, Ting S, Lei X, Ding X, Sci. Rep., 8(1), 2518 (2018)

[5] Rosova I, Dao M, Capoccia B, Link D, Nolta JA, Stem Cells, 26, 2173 (2008)

[6] Bhang SH, Lee S, Shin JYU, Lee TJ, Kim BS, Tissue Eng Part A, 18(19-20), 2138 (2012)

[7] Dai Y, Xu M, Wang Y, Pasha Z, Li T, Ashraf M, J. Mol. Cell. Cardiol., 42(6), 1036 (2007)

[8] Nelson CM, Chen CS, Febs Lett., 514(2-3), 238 (2002)

[9] Wei Q, Hariharan V, Huang H, PLoS ONE, 6(10), e27064 (2011)

[10] Balcioglu HE, van de Water B, Danen EH, Sci. Rep., 6(1), 22580 (2016)

[11] Zhou Z, Chen Y, Chai M, Tao R, Lei Y, Jia Y, Shu J, Ren J, Li G, Wei W, Han Y, Han Y, Int. J. Mol. Med., 43(2), 890 (2019)

[12] Petrenko Y, Sykova E, Kubinova S, Stem Cell Res. Ther., 8(1), 94 (2017)

[13] Santos JM, Camoes SP, Filipe E, Cipriano M, Barcia RN, Filipe M, Teixeira M, et al., Stem Cell Res. Ther., 6, 90 (2015)

[14] Xu Y, Shi T, Xu A, Zhang L, J. Cell. Mol. Med., 20(7), 1203 (2016)

[15] Sankar S, Sharma CS, Rath SN, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 94, 703 (2019)

[16] Tseng TC, Hsu SH, Biomaterials, 35(9), 2630 (2014)

[17] Park IS, Chung PS, Ahn JC, Biomaterials, 35(34), 9280 (2014)

[18] Regmi S, Pathak S, Thanh TP, Nguyen TT, Sung JH, Yook S, Kim JO, et al., Stem Cell Res. Ther., 10(1), 230 (2019)

[19] Tsai CC, Hong YJ, Lee RJ, Cheng NC, Yu J, J. Mater. Chem. B, 7(7), 1064 (2019)

[20] Chung EJ, Choi JS, Shin JS, Cho HN, Kim SY, Park JY, Lee YS, Kim YI, Wu HG, Cho SW, Kwon SK, J. Ind. Eng. Chem., 90, 47 (2020)

[21] Perikamana SKM, Kim J, Park SY, Jung HS, Shin H, J. Ind. Eng. Chem., 80, 784 (2019)

[22] Shan X, Choi JH, Kim KJ, Lee YJ, Ryu YH, Lee SJ, Moon SH, Rhie JW, Tissue Eng. Regen. Med., 15, 49 (2018)

[23] Hwang OK, Noh YW, Hong JT, Lee JW, Tissue Eng. Regen. Med, 17, 335 (2020)

[24] Furuhata Y, Kikuchi Y, Tomita S, Yoshimoto K, Genes Cells, 21(12), 1380 (2016)

[25] Jensen MM, Jørgensen JT, Binderup T, Kjær A, BMC Med. Imaging, 8(1) (2008)

[26] Guo L, Zhou Y, Wang S, Wu Y, J. Cell. Mol. Med., 18(10), 2009 (2014)

[27] Bartosh TJ, Ylostalo JH, Mohammadipoor A, Bazhanov N, Coble K, Claypool K, Lee RH, Choi H, Prockop DJ, Proc. Natl. Acad. Sci. U. S. A., 107(31), 13724 (2010)

[28] Banerjee M, Bhonde RR, Cytotechnology, 51(1), 1 (2006)

[29] Miriam JS, Front. Cell. Dev. Biol., 3, 42 (2015)

[30] Razban V, Lotfi AS, Soleimani M, Ahmadi H, Massumi M, Khajeh S, Ghaedi M, Arjmand S, Najavand S, Khoshdel A, Biores. Open Access, 1(4), 174 (2012)

[31] Langan LM, Dodd NJ, Owen SF, Purcell WM, Jackson SK, Jha AN, PLoS One, 11(2), e01494 (2016)

[32] Brian AA, Widya M, James S, Kyle JL, Sarah CH, Tissue Eng. Part A, 18(7-8), 806 (2012)

[33] Lin RZ, Ho CT, Liu CH, Chang HY, Cell Tissue Res., 324, 411 (2006)

[34] Ishikawa M, Iwamoto T, Nakamura T, Doyle A, Fukumoto S, Yamada Y, J. Cell Biol., 193(7), 1257 (2011)

[35] Bao BA, Lai CP, Naus CC, Morgan JR, J. Biol. Chem., 287(11), 8407 (2012)

[36] Nishihira S, Okubo N, Takahashi N, Ishisaki A, Sugiyama Y, Chosa N, Cell Biol. Int., 35(5), 475 (2011)

[37] Chosa N, Ishisaki A, Jpn. Dent. Sci. Rev., 54(1), 37 (2018)

[38] Gerber HP, Dixit V, Ferrara N, J. Biol. Chem., 273(21), 13313 (1998)

[39] Joshi P, Lee MY, Biosensors, 5(4), 768 (2015)

[40] Fennema E, Rivron N, Rouwkema J, van Blitterswijk C, de Boer J, Trends Biotechnol., 31(2), 108 (2013)

[41] Katt ME, Placone AL, Wong AD, Xu ZS, Searson PC. Front. Bioeng. Biotechnol., 4 (2016).

[42] Boucher J, Simonneau C, Denet G, Clarhaut J, Balandre AC, Mesnil M, Cronier L, Monvoisin A, Int. J. Mol. Sci., 19(6), 1588 (2018)

[43] Du W, Li X, Chi Y, Ma F, Li Z, Yang S, Song B, Cui J, Ma T, Li J, Tian J, Yang Z, Feng X, Chen F, Lu S, Liang L, Han ZB, Han ZC, Stem Cell Res. Ther., 7(1), 49 (2016)

[44] Wang CM, Guo Z, Xie YJ, Hao YY, Sun JM, Gu J, Wang AL, Mol. Med. Rep., 10(2), 792 (2014)

[45] Suzuki H, Murakami M, Shoji M, Iso Y, Kondo T, Shibata M, Ezumi H, Hamazaki Y, Koba S, Katagiri T, Coron. Artery Dis., 14(4), 301 (2003)

[46] Meirelles LS, Fontes AM, Covas DT, Caplan AI, Cytokine Growth Factor Rev., 20(5-6), 419 (2009)

[47] Sun M, He Y, Zhou T, Zhang P, Gao J, Lu F, Biomed. Res. Int, 2017, 1 (2017)

[48] Guc E, Briquez PS, Foretay D, Fankhauser MA, Hubbell JA, Kilarski WW, Swartz MA, Biomaterials, 131, 160 (2017)

[49] Welford SM, Giaccia AJ, Mol. Cancer Res., 9(5), 538 (2011)

[50] Santilli G, Lamorte G, Carlessi L, Ferrari D, Rota Nodari L, Binda E, Delia D, Vescovi AL, De Filippis L, PLoS ONE, 5(1), e8575 (2010)

[51] Song YS, Joo HW, Park IH, Shen GY, Lee Y, Shin JH, Kim H, Kim KS, PLOS ONE, 12(6), e01799 (2017)

[52] Nita I, Hostettler K, Tamo L, Medova M, Bombaci G, Zhong J, Allam R, Zimmer Y, Roth M, Geiser T, Gazdhar A, Sci Rep., 7, 41901 (2017)