Union is strength: matrix elasticity and microenvironmental factors codetermine stem cell differentiation fate
Stem cells are an attractive cellular source for regenerative medicine and tissue engineering applications due to their multipotency. Although the elasticity of the extracellular matrix (ECM) has been shown to have crucial impacts in directing stem cell differentiation, it is not the only contributing factor. Many researchers have recently attempted to design microenvironments that mimic the stem cell niche with combinations of ECM elasticity and other cues, such as ECM physical properties, soluble biochemical factors and cell–cell interactions, thereby driving cells towards their preferred lineages. Here, we briefly discuss the effect of matrix elasticity on stem cell lineage specification and then summarize recent advances in the study of the combined effects of ECM elasticity and other cues on the differentiation of stem cells, focusing on two aspects: biophysical and biochemical factors. In the future, biomedical scientists will continue investigating the union strength of matrix elasticity and microenvironmental cues for manipulating stem cell fates.
KeywordsMatrix elasticity Biophysical factor Biochemical factor Stem cells Differentiation
The authors thank William Orr, M.D., University of Manitoba, Winnipeg, Canada, for his assistance in writing. This work was supported by the State Key Development Program for Basic Research of China (Grant No. 2011CB606201), the National Natural Science Foundation of China (Grant No. 31150007, 31201052), China Postdoctoral Science Foundation (Grant No. 20090450415 and 201003125), Bethune Medical Research Support Program and Advanced Interdisciplinary Innovation Project (Grant No. 2013101004).
Conflicts of interest
The authors declare no potential conflicts of interest.
- Alkhouli N, Mansfield J, Green E, Bell J, Knight B, Liversedge N, Tham JC, Welbourn R, Shore AC, Kos K, Winlove CP (2013) The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix. Am J Physiol Endocrinol Metab 305:E1427–E1435CrossRefPubMedGoogle Scholar
- Bajpai VK, Andreadis ST (2012) Stem cell sources for vascular tissue engineering and regeneration. Tissue Eng B 18:405–425Google Scholar
- Cao N, Liu ZM, Chen ZY, Wang J, Chen TT, Zhao XY, Ma Y, Qin LJ, Kang JH, Wei B, Wang L, Jin Y, Yang HT (2012) Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells. Cell Res 22:219–236PubMedCentralCrossRefPubMedGoogle Scholar
- Cheng XG, Tsao C, Sylvia VL, Cornet D, Nicolella DP, Bredbenner TL, Christy RJ (2014) Platelet-derived growth-factor-releasing aligned collagen-nanoparticle fibers promote the proliferation and tenogenic differentiation of adipose-derived stem cells. Acta Biomater 10:1360–1369CrossRefPubMedGoogle Scholar
- Elder BD, Athanasiou KA (2009) Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration. Tissue Eng B 15:43–53Google Scholar
- Gershlak JR, Resnikoff JIN, Sullivan KE, Williams C, Wang RM, Black LD (2013) Mesenchymal stem cells ability to generate traction stress in response to substrate stiffness is modulated by the changing extracellular matrix composition of the heart during development. Biochem Biophys Res Commun 439:161–166CrossRefPubMedGoogle Scholar
- Kim MJ, Shin KS, Jeon JH, Lee DR, Shim SH, Kim JK, Cha DH, Yoon TK, Kim GJ (2011) Human chorionic-plate-derived mesenchymal stem cells and Wharton’s jelly-derived mesenchymal stem cells: a comparative analysis of their potential as placenta-derived stem cells. Cell Tissue Res 346:53–64CrossRefPubMedGoogle Scholar
- Kraehenbuehl TP, Zammaretti P, Van der Vlies AJ, Schoenmakers RG, Lutolf MP, Jaconi ME, Hubbell JA (2008) Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: systematic modulation of a synthetic cell-responsive PEG-hydrogel. Biomaterials 29:2757–2766CrossRefPubMedGoogle Scholar
- Kshitiz, Hubbi ME, Ahn EH, Downey J, Afzal J, Kim DH, Rey S, Chang C, Kundu A, Semenza GL, Abraham RM, Levchenko A (2012) Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors. Sci Signal 5: ra41Google Scholar
- Prosecka E, Rampichova M, Vojtova L, Tvrdik D, Melcakova S, Juhasova J, Plencner M, Jakubova R, Jancar J, Necas A, Kochova P, Klepacek J, Tonar Z, Amler E (2011) Optimized conditions for mesenchymal stem cells to differentiate into osteoblasts on a collagen/hydroxyapatite matrix. J Biomed Mater Res A 99A:307–315CrossRefGoogle Scholar
- Shi Y, Glaser KJ, Venkatesh SK, Ben-Abraham EI, Ehman RL (2015) Feasibility of using 3D MR elastography to determine pancreatic stiffness in healthy volunteers. J Magn Reson Imaging 41:369–375Google Scholar
- Sun H, Hou Z, Yang H, Meng M, Li P, Zou Q, Yang L, Chen Y, Chai H, Zhong H, Yang ZZ, Zhao J, Lai L, Jiang X, Xiao Z (2014) Multiple systemic transplantations of human amniotic mesenchymal stem cells exert therapeutic effects in an ALS mouse model. Cell Tissue Res 357:571–582CrossRefPubMedGoogle Scholar
- Swift J, Ivanovska IL, Buxboim A, Harada T, Dingal PCDP, Pinter J, Pajerowski JD, Spinler KR, Shin JW, Tewari M, Rehfeldt F, Speicher DW, Discher DE (2013) Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341:1240104PubMedCentralCrossRefPubMedGoogle Scholar
- Zouani OF, Kalisky J, Ibarboure E, Durrieu MC (2013) Effect of BMP-2 from matrices of different stiffnesses for the modulation of stem cell fate. Biomaterials 34:2157–2166Google Scholar