Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

A Novel Multi-compartment Rotating Bioreactor for Improving ADSC-Spheroid Formation and its Application in Neurogenic Erectile Dysfunction

Author(s): Peng Wang, Yang Liu, Xiao-Feng Duan, Xiao-Ying Pan, Xiang-Rui Kong and Yong Yang*

Volume 19, Issue 10, 2024

Published on: 04 January, 2024

Page: [1382 - 1392] Pages: 11

DOI: 10.2174/011574888X253599231126161254

Price: $65

Abstract

Objective: The aim of this study was to construct a multicompartment synchronous rotating bioreactor (MCSRB) for batch-production of homogenized adipose-derived stem cell (ADSC) microspheres and treat neurogenic erectile dysfunction (ED).

Methods: Firstly, an MCSRB was constructed using a centrifugal device and hinged trays. Secondly, influence factors (density, rotational speed) on the formation of ADSC-spheroids were explored. Finally, a neurogenic ED model was established to verify the effectiveness and safety of ADSC-spheroids for ED treatment.

Results: An MCSRB promoted ADSCs to gather microspheres, most of which were 90-130 μm in diameter. Supernatant from three-dimensional culture led to a significant increase in cytokine expression in ADSCs and migration rate in human umbilical vein endothelial cells (HUVECs) compared to control groups. The erectile function and pathological changes of the penis were improved in the ADSC-spheroids treatment group compared to the traditional ADSCs treatment group (p < 0.01).

Conclusion: Efficient, batch, controlled and homogenized production of ADSC stem cell microspheres, and effective improvement of erectile dysfunction in neurogenic rats can be achieved using the MCSRB device.

« Previous Next »
[1]
Zhang, H.; Yang, R.; Wang, Z.; Lin, G.; Lue, T.F.; Lin, C.S. Adipose tissue-derived stem cells secrete CXCL5 cytokine with neurotrophic effects on cavernous nerve regeneration. J. Sex. Med., 2011, 8(2), 437-446.
[http://dx.doi.org/10.1111/j.1743-6109.2010.02128.x] [PMID: 21114767]
[2]
Matsuda, Y.; Sasaki, M.; Kataoka-Sasaki, Y.; Takayanagi, A.; Kobayashi, K.; Oka, S.; Nakazaki, M.; Masumori, N.; Kocsis, J.D.; Honmou, O. Intravenous infusion of bone marrow–derived mesenchymal stem cells reduces erectile dysfunction following cavernous nerve injury in rats. Sex. Med., 2018, 6(1), 49-57.
[http://dx.doi.org/10.1016/j.esxm.2017.10.005] [PMID: 29275062]
[3]
Jung, J.W.; Kwon, M.; Choi, J.C.; Shin, J.W.; Park, I.W.; Choi, B.W.; Kim, J.Y. Familial occurrence of pulmonary embolism after intravenous, adipose tissue-derived stem cell therapy. Yonsei Med. J., 2013, 54(5), 1293-1296.
[http://dx.doi.org/10.3349/ymj.2013.54.5.1293] [PMID: 23918585]
[4]
Xu, Y.; Yang, Y.; Zheng, H.; Huang, C.; Zhu, X.; Zhu, Y.; Guan, R.; Xin, Z.; Liu, Z.; Tian, Y. Intracavernous injection of size-specific stem cell spheroids for neurogenic erectile dysfunction: Efficacy and risk versus single cells. EBioMedicine, 2020, 52, 102656.
[http://dx.doi.org/10.1016/j.ebiom.2020.102656] [PMID: 32062355]
[5]
Bhang, S.H.; Cho, S.W.; La, W.G.; Lee, T.J.; Yang, H.S.; Sun, A.Y.; Baek, S.H.; Rhie, J.W.; Kim, B.S. Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells. Biomaterials, 2011, 32(11), 2734-2747.
[http://dx.doi.org/10.1016/j.biomaterials.2010.12.035] [PMID: 21262528]
[6]
Bartosh, T.J.; Ylöstalo, J.H.; Mohammadipoor, A.; Bazhanov, N.; Coble, K.; Claypool, K.; Lee, R.H.; Choi, H.; Prockop, D.J. Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc. Natl. Acad. Sci., 2010, 107(31), 13724-13729.
[http://dx.doi.org/10.1073/pnas.1008117107] [PMID: 20643923]
[7]
Qiao, Y.; Xu, Z.; Yu, Y.; Hou, S.; Geng, J.; Xiao, T.; Liang, Y.; Dong, Q.; Mei, Y.; Wang, B.; Qiao, H.; Dai, J.; Suo, G. Single cell derived spheres of umbilical cord mesenchymal stem cells enhance cell stemness properties, survival ability and therapeutic potential on liver failure. Biomaterials, 2020, 227, 119573.
[http://dx.doi.org/10.1016/j.biomaterials.2019.119573] [PMID: 31670080]
[8]
Fuentes, P.; Torres, M.J.; Arancibia, R.; Aulestia, F.; Vergara, M.; Carrión, F.; Osses, N.; Altamirano, C. Dynamic culture of mesenchymal stromal/stem cell spheroids and secretion of paracrine factors. Front. Bioeng. Biotechnol., 2022, 10, 916229.
[http://dx.doi.org/10.3389/fbioe.2022.916229] [PMID: 36046670]
[9]
Ryu, N.E.; Lee, S.H.; Park, H. Spheroid culture system methods and applications for mesenchymal stem cells. Cells, 2019, 8(12), 1620.
[http://dx.doi.org/10.3390/cells8121620] [PMID: 31842346]
[10]
Wang, W.; Itaka, K.; Ohba, S.; Nishiyama, N.; Chung, U.; Yamasaki, Y.; Kataoka, K. 3D spheroid culture system on micropatterned substrates for improved differentiation efficiency of multipotent mesenchymal stem cells. Biomaterials, 2009, 30(14), 2705-2715.
[http://dx.doi.org/10.1016/j.biomaterials.2009.01.030] [PMID: 19215979]
[11]
Chan, H.F.; Zhang, Y.; Ho, Y.P.; Chiu, Y.L.; Jung, Y.; Leong, K.W. Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment. Sci. Rep., 2013, 3(1), 3462.
[http://dx.doi.org/10.1038/srep03462] [PMID: 24322507]
[12]
Kim, S.; Kim, E.M.; Yamamoto, M.; Park, H.; Shin, H. Engineering multi-cellular spheroids for tissue engineering and regenerative medicine. Adv. Healthc. Mater., 2020, 9(23), 2000608.
[http://dx.doi.org/10.1002/adhm.202000608] [PMID: 32734719]
[13]
Megaloikonomos, P.D.; Panagopoulos, G.N.; Bami, M.; Igoumenou, V.G.; Dimopoulos, L.; Milonaki, A.; Kyriakidou, M.; Mitsiokapa, E.; Anastassopoulou, J.; Mavrogenis, A.F. Harvesting, isolation and differentiation of rat adipose-derived stem cells. Curr. Pharm. Biotechnol., 2018, 19(1), 19-29.
[http://dx.doi.org/10.2174/1389201019666180418101323] [PMID: 29667552]
[14]
Yang, W.; Chen, Z.; Ma, X.; Ouyang, X.; Fang, J.; Wei, H. Co-overexpression of VEGF and GDNF in adipose-derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model. Cell Prolif., 2020, 53(2), e12756.
[http://dx.doi.org/10.1111/cpr.12756] [PMID: 31943490]
[15]
Bunnell, B.; Flaat, M.; Gagliardi, C.; Patel, B.; Ripoll, C. Adipose-derived stem cells: Isolation, expansion and differentiation. Methods, 2008, 45(2), 115-120.
[http://dx.doi.org/10.1016/j.ymeth.2008.03.006] [PMID: 18593609]
[16]
Liu, Y.; Pan, X.; Zhang, X.; Sun, J.; Mao, Y.; Yang, Y.; Wei, Z. Role of mechanotransduction mediated by YAP/TAZ in the treatment of neurogenic erectile dysfunction with low-intensity pulsed ultrasound. Andrology, 2023, 11(7), 1514-1527.
[http://dx.doi.org/10.1111/andr.13438] [PMID: 37042189]
[17]
Liu, Y.; Wei, Z.; Liu, S.; Sun, J.; Mao, Y.; Xu, Y.; Yang, Y. A flavonoid derivative of icariside II (YS-10) improves erectile dysfunction in radiation-injured rats via oxidative stress pathway. Transl. Androl. Urol., 2022, 11(6), 832-841.
[http://dx.doi.org/10.21037/tau-22-376] [PMID: 35812197]
[18]
Paschos, N.K.; Brown, W.E.; Eswaramoorthy, R.; Hu, J.C.; Athanasiou, K.A. Advances in tissue engineering through stem cell-based co- culture. J. Tissue Eng. Regen. Med., 2015, 9(5), 488-503.
[http://dx.doi.org/10.1002/term.1870] [PMID: 24493315]
[19]
Kim, E.M.; Lee, G.M.; Lee, S.; Kim, S.; Lee, D.; Yoon, D.S.; Joo, J.; Kong, H.; Park, H.H.; Shin, H. Effects of mechanical properties of gelatin methacryloyl hydrogels on encapsulated stem cell spheroids for 3D tissue engineering. Int. J. Biol. Macromol., 2022, 194, 903-913.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.11.145] [PMID: 34838857]
[20]
Virdi, J.K.; Pethe, P. Biomaterials regulate mechanosensors YAP/TAZ in stem cell growth and differentiation. Tissue Eng. Regen. Med., 2021, 18(2), 199-215.
[http://dx.doi.org/10.1007/s13770-020-00301-4] [PMID: 33230800]
[21]
Martin, S.; Harrington, D.A.; Ohlander, S.; Stupp, S.I.; McVary, K.T.; Podlasek, C.A. Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction. Nanomedicine, 2021, 37, 102444.
[http://dx.doi.org/10.1016/j.nano.2021.102444] [PMID: 34314869]
[22]
Hsu, T.W.; Lu, Y.J.; Lin, Y.J.; Huang, Y.T.; Hsieh, L.H.; Wu, B.H.; Lin, Y.C.; Chen, L.C.; Wang, H.W.; Chuang, J.C.; Fang, Y.Q.; Huang, C.C. Transplantation of 3D MSC/HUVEC spheroids with neuroprotective and proangiogenic potentials ameliorates ischemic stroke brain injury. Biomaterials, 2021, 272, 120765.
[http://dx.doi.org/10.1016/j.biomaterials.2021.120765] [PMID: 33780686]
[23]
Kodali, A.; Lim, T.C.; Leong, D.T.; Tong, Y.W. Cell-microsphere constructs formed with human adipose-derived stem cells and gelatin microspheres promotes stemness, differentiation, and controlled pro-angiogenic potential. Macromol. Biosci., 2014, 14(10), 1458-1468.
[http://dx.doi.org/10.1002/mabi.201400094] [PMID: 24986523]
[24]
Zhang, S.; Liu, P.; Chen, L.; Wang, Y.; Wang, Z.; Zhang, B. The effects of spheroid formation of adipose-derived stem cells in a microgravity bioreactor on stemness properties and therapeutic potential. Biomaterials, 2015, 41, 15-25.
[http://dx.doi.org/10.1016/j.biomaterials.2014.11.019] [PMID: 25522961]
[25]
Chen, Y.; Zhang, L.; Liu, W.; Wang, K. VEGF and SEMA4D have synergistic effects on the promotion of angiogenesis in epithelial ovarian cancer. Cell. Mol. Biol. Lett., 2018, 23(1), 2.
[http://dx.doi.org/10.1186/s11658-017-0058-9] [PMID: 29308068]
[26]
Lai, F.; Wang, J.; Tang, H.; Huang, P.; Liu, J.; He, G.; Zhou, M.; Tao, X.; Tang, K. VEGF promotes tendon regeneration of aged rats by inhibiting adipogenic differentiation of tendon stem/progenitor cells and promoting vascularization. FASEB J., 2022, 36(8), e22433.
[http://dx.doi.org/10.1096/fj.202200213R] [PMID: 35867348]
[27]
Nejabati, H.R.; Latifi, Z.; Ghasemnejad, T.; Fattahi, A.; Nouri, M. Placental growth factor (PlGF) as an angiogenic/inflammatory switcher: lesson from early pregnancy losses. Gynecol. Endocrinol., 2017, 33(9), 668-674.
[http://dx.doi.org/10.1080/09513590.2017.1318375] [PMID: 28447504]
[28]
Desole, C.; Gallo, S.; Vitacolonna, A.; Montarolo, F.; Bertolotto, A.; Vivien, D.; Comoglio, P.; Crepaldi, T. HGF and MET: From brain development to neurological disorders. Front. Cell Dev. Biol., 2021, 9, 683609.
[http://dx.doi.org/10.3389/fcell.2021.683609] [PMID: 34179015]
[29]
Ying, C-C.; Yang, M.; Sun, J-Y.; Wang, Y.; Guo, Y.L. Adipose-derived stem cells modified by BDNF gene rescue erectile dysfunction after cavernous nerve injury. Neural Regen. Res., 2020, 15(1), 120-127.
[http://dx.doi.org/10.4103/1673-5374.264464] [PMID: 31535660]
[30]
Jiang, W.; Zhang, J.; Zhang, X.; Fan, C.; Huang, J. VAP-PLGA microspheres (VAP-PLGA) promote adipose-derived stem cells (ADSCs)-induced wound healing in chronic skin ulcers in mice via PI3K/Akt/HIF-1α pathway. Bioengineered, 2021, 12(2), 10264-10284.
[http://dx.doi.org/10.1080/21655979.2021.1990193] [PMID: 34720043]
[31]
Wani, M.M.; Rai, B.P.; Webb, W.R.; Madaan, S. Is there a role for stem cell therapy in erectile dysfunction secondary to cavernous nerve injury? Network meta-analysis from animal studies and human trials. Ther. Adv. Urol., 2022, 14
[http://dx.doi.org/10.1177/17562872221086999] [PMID: 35371295]
[32]
Yan, H.; Ding, Y.; Lu, M. Current status and prospects in the treatment of erectile dysfunction by adipose-derived stem cells in the diabetic animal model. Sex. Med. Rev., 2020, 8(3), 486-491.
[http://dx.doi.org/10.1016/j.sxmr.2019.09.006] [PMID: 31980404]
[33]
Zheng, H.; Bai, Z.; Xu, Y.; Sun, J.; Lu, L.; Yang, Y. Effects of cells self-aggregation in the treatment of neurogenic erectile dysfunction with traditional single cell suspension of adipose-derived stem cells. Urology, 2021, 158, 102-109.
[http://dx.doi.org/10.1016/j.urology.2021.09.002] [PMID: 34536411]
[34]
Chen, Y.L.; Chao, T.T.; Wu, Y.N.; Chen, M.C.; Lin, Y.H.; Liao, C.H.; Wu, C.C.; Chen, K.C.; Chou, S.S.P.; Chiang, H.S. nNOS-positive minor-branches of the dorsal penile nerves is associated with erectile function in the bilateral cavernous injury model of rats. Sci. Rep., 2018, 8(1), 929.
[http://dx.doi.org/10.1038/s41598-017-18988-2] [PMID: 29343793]
[35]
Haney, N.M.; Talwar, S.; Akula, P.K.; Reddy, A.G.; Pema, G.S.; Ninh, T.V.; Rezk, B.M.; Heidari, Z.; Bouljihad, M.T.; Sikka, S.C.; John, V.; Abdel-Mageed, A.B.; Hellstrom, W.J.G. Insulin-like growth factor-1–loaded polymeric poly(Lactic-Co-Glycolic) acid microspheres improved erectile function in a rat model of bilateral cavernous nerve injury. J. Sex. Med., 2019, 16(3), 383-393.
[http://dx.doi.org/10.1016/j.jsxm.2018.12.018] [PMID: 30846112]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy