Abstract
In vivo, all stem cells reside within distinct and defined microenvironments referred to as stem cell niches. Complex interactions between stem cells and their niche tightly regulate cell fate decisions. This affects live/death decisions, cellular senescence, and cell differentiation. Therefore, removing mesenchymal stromal/stem cells (MSCs) from their niche and cultivation within conventional flat, two-dimensional (2D) cell culture systems affects their cell fate and therefore also their regenerative potential. Nevertheless, routine MSC culture for research and therapy is still conducted in 2D. Three-dimensional (3D) cell culture is a state-of-the-art technology allowing expanding and differentiating MSCs under more physiological conditions. This chapter will summarize current understanding of the impact of 3D cell culture on fundamental properties of MSCs including their proliferation, viability, cellular senescence, and differentiation. Furthermore, effects of 3D cell culture on the immunomodulatory and anti-inflammatory potential of MSCs will be evaluated.
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Abbreviations
- 2D:
-
Two-dimensional
- 3D:
-
Three-dimensional
- AD-MSCs:
-
Adipose tissue-derived MSCs
- ALP:
-
Alkaline phosphatase
- IL-10:
-
Interleukin-10
- IL-24:
-
Interleukin-24
- IL-1β:
-
Interleukin-1β
- IL-6:
-
Interleukin-6
- LIF:
-
Leukemia inhibitory factor
- MCP-1:
-
Monocyte chemoattractant protein-1
- M-CSF:
-
Macrophage colony stimulating factor
- MSCs:
-
Mesenchymal stromal cells/mesenchymal stem cells
- OCN:
-
Osteocalcin
- OPN:
-
Osteopontin
- PGE-2:
-
Prostaglandin E2
- TNF-α:
-
Tumor necrosis factor-α
References
Afzal MR, Haider KH, Niagara MI, Jiang S, Ahmed RPH, Ashraf M (2010) Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in infarcted heart via NF-кB signaling. Antioxid Redox Signal 12(6):693–702
Andrzejewska A, Lukomska B, Janowski M (2019) Concise review: mesenchymal stem cells: from roots to boost. Stem Cells 37(7):855–864. https://doi.org/10.1002/stem.3016
Atoui R, Asenjo JF, Duong M, Chen G, Chiu RC, Shum-Tim D (2008a) Marrow stromal cells as universal donor cells for myocardial regenerative therapy: their unique immune tolerance. Ann Thorac Surg 85:571–580. https://doi.org/10.1016/j.athoracsur.2007.10.034
Atoui R, Shum-Tim D, Chiu RC (2008b) Myocardial regenerative therapy: immunologic basis for the potential “universal donor cells”. Ann Thorac Surg 86:327–334. https://doi.org/10.1016/j.athoracsur.2008.03.038
Azoidis I, Metcalfe J, Reynolds J, Keeton S, Hakki SS, Sheard J, Widera D (2017) Three-dimensional cell culture of human mesenchymal stem cells in nanofibrillar cellulose hydrogels. MRS Commun 7(3):458–465. https://doi.org/10.1557/mrc.2017.59
Bae YJ, Kwon YR, Kim HJ, Lee S, Kim YJ (2017) Enhanced differentiation of mesenchymal stromal cells by three-dimensional culture and azacitidine. Blood Res 52(1):18–24. https://doi.org/10.5045/br.2017.52.1.18
Bara JJ, Richards RG, Alini M, Stoddart MJ (2014) Concise review: bone marrow-derived mesenchymal stem cells change phenotype following in vitro culture: implications for basic research and the clinic. Stem Cells 32(7):1713–1723. https://doi.org/10.1002/stem.1649
Baraniak PR, McDevitt TC (2012) Scaffold-free culture of mesenchymal stem cell spheroids in suspension preserves multilineage potential. Cell Tissue Res 347(3):701–711. https://doi.org/10.1007/s00441-011-1215-5
Bartosh TJ, Ylostalo JH, Mohammadipoor A, Bazhanov N, Coble K, Claypool K, Lee RH, Choi H, Prockop DJ (2010) Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc Natl Acad Sci U S A 107(31):13724–13729. https://doi.org/10.1073/pnas.1008117107
Bartosh TJ, Ylostalo JH, Bazhanov N, Kuhlman J, Prockop DJ (2013) Dynamic compaction of human mesenchymal stem/precursor cells into spheres self-activates caspase-dependent IL1 signaling to enhance secretion of modulators of inflammation and immunity (PGE2, TSG6, and STC1). Stem Cells 31(11):2443–2456. https://doi.org/10.1002/stem.1499
Ben-David U, Mayshar Y, Benvenisty N (2011) Large-scale analysis reveals acquisition of lineage-specific chromosomal aberrations in human adult stem cells. Cell Stem Cell 9(2):97–102. https://doi.org/10.1016/j.stem.2011.06.013
Bicer M, Cottrell GS, Widera D (2021) Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells. Stem Cell Res Ther 12(1):31. https://doi.org/10.1186/s13287-020-02094-8
Bou-Ghannam S, Kim K, Grainger D, Okano T (2021) 3D cell sheet structure augments mesenchymal stem cell cytokine production. Sci Rep 11:8170. https://doi.org/10.1038/s41598-021-87571-7
Brennan MA, Renaud A, Gamblin AL, D’Arros C, Nedellec S, Trichet V, Layrolle P (2015) 3D cell culture and osteogenic differentiation of human bone marrow stromal cells plated onto jet-sprayed or electrospun micro-fiber scaffolds. Biomed Mater 10(4):045019. https://doi.org/10.1088/1748-6041/10/4/045019
Brook FA, Gardner RL (1997) The origin and efficient derivation of embryonic stem cells in the mouse. Proc Natl Acad Sci U S A 94(11):5709–5712. https://doi.org/10.1073/pnas.94.11.5709
Burand AJ Jr, Di L, Boland LK, Boyt DT, Schrodt MV, Santillan DA, Ankrum JA (2020) Aggregation of human mesenchymal stromal cells eliminates their ability to suppress human T cells. Front Immunol 11:143. https://doi.org/10.3389/fimmu.2020.00143
Carter K, Lee HJ, Na KS, Fernandes-Cunha GM, Blanco IJ, Djalilian A, Myung D (2019) Characterizing the impact of 2D and 3D culture conditions on the therapeutic effects of human mesenchymal stem cell secretome on corneal wound healing in vitro and ex vivo. Acta Biomater 99:247–257. https://doi.org/10.1016/j.actbio.2019.09.022
Cesarz Z, Tamama K (2016) Spheroid culture of mesenchymal stem cells. Stem Cells Int 2016:9176357. https://doi.org/10.1155/2016/9176357
Cheng NC, Chen SY, Li JR, Young TH (2013) Short-term spheroid formation enhances the regenerative capacity of adipose-derived stem cells by promoting stemness, angiogenesis, and chemotaxis. Stem Cells Transl Med 2(8):584–594. https://doi.org/10.5966/sctm.2013-0007
Chierchia A, Chirico N, Boeri L, Raimondi I, Riva GA, Raimondi MT, Tunesi M, Giordano C, Forloni G, Albani D (2017) Secretome released from hydrogel-embedded adipose mesenchymal stem cells protects against the Parkinson’s disease related toxin 6-hydroxydopamine. Eur J Pharm Biopharm 121:113–120. https://doi.org/10.1016/j.ejpb.2017.09.014
Cochis A, Grad S, Stoddart MJ, Fare S, Altomare L, Azzimonti B, Alini M, Rimondini L (2017) Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel. Sci Rep 7:45018. https://doi.org/10.1038/srep45018
Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, Morgan JE (2005) Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122(2):289–301. https://doi.org/10.1016/j.cell.2005.05.010
Colmone A, Amorim M, Pontier AL, Wang S, Jablonski E, Sipkins DA (2008) Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science 322(5909):1861–1865. https://doi.org/10.1126/science.1164390
Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433(7027):760–764. https://doi.org/10.1038/nature03260
Connick P, Kolappan M, Patani R, Scott MA, Crawley C, He XL, Richardson K, Barber K, Webber DJ, Wheeler-Kingshott CA, Tozer DJ, Samson RS, Thomas DL, Du MQ, Luan SL, Michell AW, Altmann DR, Thompson AJ, Miller DH, Compston A, Chandran S (2011) The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments. Trials 12:62. https://doi.org/10.1186/1745-6215-12-62
D’Ippolito G, Diabira S, Howard GA, Menei P, Roos BA, Schiller PC (2004) Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci 117(Pt 14):2971–2981. https://doi.org/10.1242/jcs.01103
Domnina A, Novikova P, Obidina J, Fridlyanskaya I, Alekseenko L, Kozhukharova I, Lyublinskaya O, Zenin V, Nikolsky N (2018) Human mesenchymal stem cells in spheroids improve fertility in model animals with damaged endometrium. Stem Cell Res Ther 9(1):50. https://doi.org/10.1186/s13287-018-0801-9
Domnina A, Ivanova J, Alekseenko L, Kozhukharova I, Borodkina A, Pugovkina N, Smirnova I, Lyublinskaya O, Fridlyanskaya I, Nikolsky N (2020) Three-dimensional compaction switches stress response programs and enhances therapeutic efficacy of endometrial mesenchymal stem/stromal cells. Front Cell Dev Biol 8:473. https://doi.org/10.3389/fcell.2020.00473
Edmondson R, Broglie JJ, Adcock AF, Yang L (2014) Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol 12(4):207–218. https://doi.org/10.1089/adt.2014.573
Favi PM, Benson RS, Neilsen NR, Hammonds RL, Bates CC, Stephens CP, Dhar MS (2013) Cell proliferation, viability, and in vitro differentiation of equine mesenchymal stem cells seeded on bacterial cellulose hydrogel scaffolds. Mater Sci Eng C Mater Biol Appl 33(4):1935–1944. https://doi.org/10.1016/j.msec.2012.12.100
Follin B, Juhl M, Cohen S, Pedersen AE, Kastrup J, Ekblond A (2016) Increased paracrine immunomodulatory potential of mesenchymal stromal cells in three-dimensional culture. Tissue Eng Part B Rev 22(4):322–329. https://doi.org/10.1089/ten.TEB.2015.0532
Foudah D, Redondo J, Caldara C, Carini F, Tredici G, Miloso M (2013) Human mesenchymal stem cells express neuronal markers after osteogenic and adipogenic differentiation. Cell Mol Biol Lett 18(2):163–186. https://doi.org/10.2478/s11658-013-0083-2
Frenette PS, Subbarao S, Mazo IB, von Andrian UH, Wagner DD (1998) Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow. Proc Natl Acad Sci U S A 95(24):14423–14428. https://doi.org/10.1073/pnas.95.24.14423
Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6(2):230–247
Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3(4):393–403. https://doi.org/10.1111/j.1365-2184.1970.tb00347.x
Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17(4):331–340. https://doi.org/10.1097/00007890-197404000-00001
Frith JE, Thomson B, Genever PG (2010) Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng Part C Methods 16(4):735–749. https://doi.org/10.1089/ten.TEC.2009.0432
Gardner OFW, Musumeci G, Neumann AJ, Eglin D, Archer CW, Alini M, Stoddart MJ (2017) Asymmetrical seeding of MSCs into fibrin-poly(ester-urethane) scaffolds and its effect on mechanically induced chondrogenesis. J Tissue Eng Regen Med 11(10):2912–2921. https://doi.org/10.1002/term.2194
Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11(4):367–368. https://doi.org/10.1038/nm0405-367
Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, Mu H, Melo LG, Pratt RE, Ingwall JS, Dzau VJ (2006) Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J 20(6):661–669. https://doi.org/10.1096/fj.05-5211com
Greiner JF, Hauser S, Widera D, Muller J, Qunneis F, Zander C, Martin I, Mallah J, Schuetzmann D, Prante C, Schwarze H, Prohaska W, Beyer A, Rott K, Hutten A, Golzhauser A, Sudhoff H, Kaltschmidt C, Kaltschmidt B (2011) Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics. Eur Cell Mater 22:403–419. https://doi.org/10.22203/ecm.v022a30
Haider KH, Aramini B (2020) “Mircrining” the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy. Stem Cell Res Ther 11:23, 1–12
Haider KH, Aslam M (2018) Cell-free therapy with stem cell secretions: protection, repair and regeneration of the injured myocardium. In: Husnain Haider K, Aziz S (eds) Stem cells: from hype to real hope. Medicine & Life Sciences, DE GRUYTER, Berlin. (Published, 2018)
Haider KH, Aziz S (2017) Paracrine hypothesis and cardiac repair. Int J Stem Cell Res Transplant 5(1):265–267
Haider KH, Jiang S, Niagara MI, Ashraf M (2008) IGF-I over expressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1α/CXCR4 signaling to promote myocardial repair. Circ Res 103:1300–1308
Han S, Zhao Y, Xiao Z, Han J, Chen B, Chen L, Dai J (2012) The three-dimensional collagen scaffold improves the stemness of rat bone marrow mesenchymal stem cells. J Genet Genomics 39(12):633–641. https://doi.org/10.1016/j.jgg.2012.08.006
Hauser S, Widera D, Qunneis F, Muller J, Zander C, Greiner J, Strauss C, Luningschror P, Heimann P, Schwarze H, Ebmeyer J, Sudhoff H, Arauzo-Bravo MJ, Greber B, Zaehres H, Scholer H, Kaltschmidt C, Kaltschmidt B (2012) Isolation of novel multipotent neural crest-derived stem cells from adult human inferior turbinate. Stem Cells Dev 21(5):742–756. https://doi.org/10.1089/scd.2011.0419
Ho SS, Murphy KC, Binder BY, Vissers CB, Leach JK (2016) Increased survival and function of mesenchymal stem cell spheroids entrapped in instructive alginate hydrogels. Stem Cells Transl Med 5(6):773–781. https://doi.org/10.5966/sctm.2015-0211
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418(6893):41–49. http://www.nature.com/nature/journal/v418/n6893/suppinfo/nature00870_S1.html
Johansson CB, Svensson M, Wallstedt L, Janson AM, Frisen J (1999) Neural stem cells in the adult human brain. Exp Cell Res 253(2):733–736. https://doi.org/10.1006/excr.1999.4678
Kalou YMN, Hashemi ASA, Joudeh R, Aramini B, Haider KH (2021) Mesenchymal stem cell-based heart cell therapy: the effect of route of cell delivery in the clinical perspective. In: Haider KH (ed) Stem cells: from potential to promise. Springer NATURE., Chapter 6, pp 151–191
Kharaziha P, Hellstrom PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR, Soleimani M (2009) Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol 21(10):1199–1205. https://doi.org/10.1097/MEG.0b013e32832a1f6c
Kim HW, Haider KH, Jiang S, Ashraf M (2009) Ischemic preconditioning augments survival of stem cells via miR-107 and miR-210 expression. J Biol Chem 284:33161–33168
Kim JH, Park IS, Park Y, Jung Y, Kim SH, Kim SH (2013) Therapeutic angiogenesis of three-dimensionally cultured adipose-derived stem cells in rat infarcted hearts. Cytotherapy 15(5):542–556. https://doi.org/10.1016/j.jcyt.2012.11.016
Kusuma G, Li A, Zhu D, McDonald H, Chambers D, Frith J, Lim R (2020) Engineering mesenchymal stem cell paracrine activity with 3D culture. Cytotherapy 22(5, Suppl):S51. https://doi.org/10.1016/j.jcyt.2020.03.064
Lee J, Cuddihy MJ, Kotov NA (2008) Three-dimensional cell culture matrices: state of the art. Tissue Eng Part B Rev 14(1):61–86. https://doi.org/10.1089/teb.2007.0150
Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, Semprun-Prieto L, Delafontaine P, Prockop DJ (2009) Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell 5(1):54–63. https://doi.org/10.1016/j.stem.2009.05.003
Lee JH, Han YS, Lee SH (2016) Long-duration three-dimensional spheroid culture promotes angiogenic activities of adipose-derived mesenchymal stem cells. Biomol Ther (Seoul) 24(3):260–267. https://doi.org/10.4062/biomolther.2015.146
Lo YP, Liu YS, Rimando MG, Ho JH, Lin KH, Lee OK (2016) Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells. Sci Rep 6:21253. https://doi.org/10.1038/srep21253
Lu G, Haider KH, Jiang S, Ashraf M (2009) Sca-1+ stem cell survival and engraftment in the infarcted heart: dual role for preconditioning-induced connexin-43. Circulation 119(19):2587–2596
Lu G, Haider KH, Porollo A, Ashraf M (2010) Mitochondria specific transgenic overexpression of connexin-43 simulates preconditioning induced cytoprotection of stem cells. Cardiovasc Res 88:277–286
Lund AW, Stegemann JP, Plopper GE (2009) Mesenchymal stem cells sense three dimensional type I collagen through discoidin domain receptor 1. Open Stem Cell J 1:40–53. https://doi.org/10.2174/1876893800901010040
Mathiasen AB, Qayyum AA, Jorgensen E, Helqvist S, Fischer-Nielsen A, Kofoed KF, Haack-Sorensen M, Ekblond A, Kastrup J (2015) Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial). Eur Heart J 36(27):1744–1753. https://doi.org/10.1093/eurheartj/ehv136
Matta C, Szűcs-Somogyi C, Kon E, Robinson D, Neufeld T, Altschuler N, Berta A et al (2019) Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells is enhanced by an aragonite scaffold. Differentiation 107:24–34. https://doi.org/10.1016/j.diff.2019.05.002
Miranda JP, Camoes SP, Gaspar MM, Rodrigues JS, Carvalheiro M, Barcia RN, Cruz P, Cruz H, Simoes S, Santos JM (2019) The secretome derived from 3D-cultured umbilical cord tissue MSCs counteracts manifestations typifying rheumatoid arthritis. Front Immunol 10:18. https://doi.org/10.3389/fimmu.2019.00018
Mirbagheri M, Adibnia V, Hughes BR, Waldman SD, Banquy X, Hwang DK (2019) Advanced cell culture platforms: a growing quest for emulating natural tissues. Mater Horiz 6(1):45–71. https://doi.org/10.1039/c8mh00803e
Miyamoto Y, Ikeuchi M, Noguchi H, Yagi T, Hayashi S (2016) Enhanced adipogenic differentiation of human adipose-derived stem cells in an in vitro microenvironment: the preparation of adipose-like microtissues using a three-dimensional culture. Cell Med 9(1–2):35–44. https://doi.org/10.3727/215517916X693096
Nguyen LT, Liao S, Chan CK, Ramakrishna S (2012) Enhanced osteogenic differentiation with 3D electrospun nanofibrous scaffolds. Nanomedicine (Lond) 7(10):1561–1575. https://doi.org/10.2217/nnm.12.41
Niibe K, Ohori-Morita Y, Zhang M, Mabuchi Y, Matsuzaki Y, Egusa H (2020) A shaking-culture method for generating bone marrow derived mesenchymal stromal/stem cell-spheroids with enhanced multipotency in vitro. Front Bioeng Biotechnol 8:590332. https://doi.org/10.3389/fbioe.2020.590332
Park H, Kim JS, Oh EJ, Kim TJ, Kim HM, Shim JH, Yoon WS, Huh JB, Moon SH, Kang SS, Chung HY (2018) Effects of three-dimensionally printed polycaprolactone/beta-tricalcium phosphate scaffold on osteogenic differentiation of adipose tissue- and bone marrow-derived stem cells. Arch Craniofac Surg 19(3):181–189. https://doi.org/10.7181/acfs.2018.01879
Persson M, Lehenkari PP, Berglin L, Turunen S, Finnila MAJ, Risteli J, Skrifvars M, Tuukkanen J (2018) Osteogenic differentiation of human mesenchymal stem cells in a 3D woven scaffold. Sci Rep 8(1):10457. https://doi.org/10.1038/s41598-018-28699-x
Rampichova M, Chvojka J, Buzgo M, Prosecka E, Mikes P, Vyslouzilova L, Tvrdik D, Kochova P, Gregor T, Lukas D, Amler E (2013) Elastic three-dimensional poly (epsilon-caprolactone) nanofibre scaffold enhances migration, proliferation and osteogenic differentiation of mesenchymal stem cells. Cell Prolif 46(1):23–37. https://doi.org/10.1111/cpr.12001
Redondo-Castro E, Cunningham CJ, Miller J, Brown H, Allan SM, Pinteaux E (2018) Changes in the secretome of tri-dimensional spheroid-cultured human mesenchymal stem cells in vitro by interleukin-1 priming. Stem Cell Res Ther 9(1):11. https://doi.org/10.1186/s13287-017-0753-5
Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255(5052):1707–1710. https://doi.org/10.1126/science.1553558
Schofield R (1978) The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4(1–2):7–25
Scuteri A, Miloso M, Foudah D, Orciani M, Cavaletti G, Tredici G (2011) Mesenchymal stem cells neuronal differentiation ability: a real perspective for nervous system repair? Curr Stem Cell Res Ther 6(2):82–92
Sefcik LS, Neal RA, Kaszuba SN, Parker AM, Katz AJ, Ogle RC, Botchwey EA (2008) Collagen nanofibres are a biomimetic substrate for the serum-free osteogenic differentiation of human adipose stem cells. J Tissue Eng Regen Med 2(4):210–220. https://doi.org/10.1002/term.85
Shahini A, Yazdimamaghani M, Walker KJ, Eastman MA, Hatami-Marbini H, Smith BJ, Ricci JL, Madihally SV, Vashaee D, Tayebi L (2014) 3D conductive nanocomposite scaffold for bone tissue engineering. Int J Nanomedicine 9:167–181. https://doi.org/10.2147/IJN.S54668
Sharma RR, Pollock K, Hubel A, McKenna D (2014) Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices. Transfusion 54(5):1418–1437. https://doi.org/10.1111/trf.12421
Sheard JJ, Bicer M, Meng Y, Frigo A, Aguilar RM, Vallance TM, Iandolo D, Widera D (2019) Optically transparent anionic nanofibrillar cellulose is cytocompatible with human adipose tissue-derived stem cells and allows simple imaging in 3D. Stem Cells Int 2019:3106929. https://doi.org/10.1155/2019/3106929
Shekaran A, Sim E, Tan KY, Chan JK, Choolani M, Reuveny S, Oh S (2015) Enhanced in vitro osteogenic differentiation of human fetal MSCs attached to 3D microcarriers versus harvested from 2D monolayers. BMC Biotechnol 15:102. https://doi.org/10.1186/s12896-015-0219-8
Shima WN, Ali AM, Subramani T, Mohamed Alitheen NB, Hamid M, Samsudin AR, Yeap SK (2015) Rapid growth and osteogenic differentiation of mesenchymal stem cells isolated from human bone marrow. Exp Ther Med 9:2202–2206
Sun Y, Wang Y, Zhou L, Zou Y, Huang G, Gao G, Ting S, Lei X, Ding X (2018) Spheroid-cultured human umbilical cord-derived mesenchymal stem cells attenuate hepatic ischemia-reperfusion injury in rats. Sci Rep 8(1):2518. https://doi.org/10.1038/s41598-018-20975-0
Takeda YS, Xu Q (2015) Neuronal differentiation of human mesenchymal stem cells using exosomes derived from differentiating neuronal cells. PLoS One 10(8):e0135111. https://doi.org/10.1371/journal.pone.0135111
Timmers L, Lim SK, Arslan F, Armstrong JS, Hoefer IE, Doevendans PA, Piek JJ, El Oakley RM, Choo A, Lee CN, Pasterkamp G, de Kleijn DP (2007) Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell Res 1(2):129–137. https://doi.org/10.1016/j.scr.2008.02.002
Tropel P, Platet N, Platel JC, Noel D, Albrieux M, Benabid AL, Berger F (2006) Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells. Stem Cells 24(12):2868–2876. https://doi.org/10.1634/stemcells.2005-0636
Tsai AC, Liu Y, Yuan X, Ma T (2015) Compaction, fusion, and functional activation of three-dimensional human mesenchymal stem cell aggregate. Tissue Eng Part A 21(9–10):1705–1719. https://doi.org/10.1089/ten.TEA.2014.0314
Turinetto V, Vitale E, Giachino C (2016) Senescence in human mesenchymal stem cells: functional changes and implications in stem cell-based therapy. Int J Mol Sci 17(7). https://doi.org/10.3390/ijms17071164
Wang XF, Song Y, Liu YS, Sun YC, Wang YG, Wang Y, Lyu PJ (2016) Osteogenic differentiation of three-dimensional bioprinted constructs consisting of human adipose-derived stem cells in vitro and in vivo. PLoS One 11(6):e0157214. https://doi.org/10.1371/journal.pone.0157214
Whitehead J, Zhang J, Harvestine JN, Kothambawala A, Liu GY, Leach JK (2020) Tunneling nanotubes mediate the expression of senescence markers in mesenchymal stem/stromal cell spheroids. Stem Cells 38(1):80–89. https://doi.org/10.1002/stem.3056
Yamaguchi Y, Ohno J, Sato A, Kido H, Fukushima T (2014) Mesenchymal stem cell spheroids exhibit enhanced in-vitro and in-vivo osteoregenerative potential. BMC Biotechnol 14:105. https://doi.org/10.1186/s12896-014-0105-9
Yin Q, Xu N, Xu D, Dong M, Shi X, Wang Y, Hao Z, Zhu S, Zhao D, Jin H, Liu W (2020) Comparison of senescence-related changes between three- and two-dimensional cultured adipose-derived mesenchymal stem cells. Stem Cell Res Ther 11(1):226. https://doi.org/10.1186/s13287-020-01744-1
Ylostalo JH, Bartosh TJ, Coble K, Prockop DJ (2012) Human mesenchymal stem/stromal cells cultured as spheroids are self-activated to produce prostaglandin E2 that directs stimulated macrophages into an anti-inflammatory phenotype. Stem Cells 30(10):2283–2296. https://doi.org/10.1002/stem.1191
Young SA, Sherman SE, Cooper TT, Brown C, Anjum F, Hess DA, Flynn LE, Amsden BG (2018) Mechanically resilient injectable scaffolds for intramuscular stem cell delivery and cytokine release. Biomaterials 159:146–160. https://doi.org/10.1016/j.biomaterials.2018.01.008
Younis LT, Abu Hassan MI, Taiyeb Ali TB, Bustami TJ (2018) 3D TECA hydrogel reduces cellular senescence and enhances fibroblasts migration in wound healing. Asian J Pharm Sci 13(4):317–325. https://doi.org/10.1016/j.ajps.2017.12.003
Yu L, Wu Y, Liu J, Li B, Ma B, Li Y, Huang Z, He Y, Wang H, Wu Z, Qiu G (2018) 3D culture of bone marrow-derived mesenchymal stem cells (BMSCs) could improve bone regeneration in 3D-printed porous Ti6Al4V scaffolds. Stem Cells Int 2018:2074021. https://doi.org/10.1155/2018/2074021
Zanini C, Bruno S, Mandili G, Baci D, Cerutti F, Cenacchi G, Izzi L, Camussi G, Forni M (2011) Differentiation of mesenchymal stem cells derived from pancreatic islets and bone marrow into islet-like cell phenotype. PLoS One 6(12):e28175. https://doi.org/10.1371/journal.pone.0028175
Zanotti L, Sarukhan A, Dander E, Castor M, Cibella J, Soldani C, Trovato AE, Ploia C, Luca G, Calvitti M, Mancuso F, Arato I, Golemac M, Jonjic N, Biondi A, Calafiore R, Locati M, D’Amico G, Viola A (2013) Encapsulated mesenchymal stem cells for in vivo immunomodulation. Leukemia 27(2):500–503. https://doi.org/10.1038/leu.2012.202
Zhang Y, Fang C, Zhang S, Campbell RE, Serpe MJ (2021) Controlled osteogenic differentiation of human mesenchymal stem cells using dexamethasone-loaded light-responsive microgels. ACS Appl Mater Interfaces 13(6):7051–7059
Zhao G, Liu F, Lan S, Li P, Wang L, Kou J, Qi X, Fan R, Hao D, Wu C, Bai T, Li Y, Liu JY (2015) Large-scale expansion of Wharton’s jelly-derived mesenchymal stem cells on gelatin microbeads, with retention of self-renewal and multipotency characteristics and the capacity for enhancing skin wound healing. Stem Cell Res Ther 6:38. https://doi.org/10.1186/s13287-015-0031-3
Zohora FT, Aldebs AI, Nosoudi N, Singh SP, Ramirez-Vick JE (2019) Gene expression profiling of human adipose tissue stem cells during 2D versus 3D adipogenesis. Cells Tissues Organs 208(3–4):113–133. https://doi.org/10.1159/000507187
Zou J, Wang W, Neffe AT, Xu X, Li Z, Deng Z, Sun X, Ma N, Lendlein A (2017) Adipogenic differentiation of human adipose derived mesenchymal stem cells in 3D architectured gelatin based hydrogels (ArcGel). Clin Hemorheol Microcirc 67(3–4):297–307. https://doi.org/10.3233/CH-179210
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Widera, D. (2022). Effects of 3D Cell Culture on the Cell Fate Decisions of Mesenchymal Stromal/Stem Cells. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_19-1
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