- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, P. R. China;
Stem cells have been regarded with promising application potential in tissue engineering and regenerative medicine due to their self-renewal and multidirectional differentiation abilities. However, their fate is relied on their local microenvironment, or niche. Recent studied have demonstrated that biophysical factors, defined as physical microenvironment in which stem cells located play a vital role in regulating stem cell committed differentiation. In vitro, synthetic physical microenvironments can be used to precisely control a variety of biophysical properties. On this basis, the effect of biophysical properties such as matrix stiffness, matrix topography and mechanical force on the committed differentiation of stem cells was further investigated. This paper summarizes the approach of mechanical models of artificial physical microenvironment and reviews the effects of different biophysical characteristics on stem cell differentiation, in order to provide reference for future research and development in related fields.
Citation: LI Chiyu, FAN Yubo, ZHENG Lisha. Differentiation of stem cells regulated by biophysical cues. Journal of Biomedical Engineering, 2023, 40(4): 609-616. doi: 10.7507/1001-5515.202208002 Copy
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2. | Abdul-Al M, Kyeremeh G K, Saeinasab M, et al. Stem cell niche microenvironment: review. Bioengineering, 2021, 8(8): 108. |
3. | Hicks M R, Pyle A D. The emergence of the stem cell niche. Trends Cell Biol, 2023, 33(2): 112-123. |
4. | Aaronson S A. Growth factors and cancer. Science, 1991, 254(5035): 1146-1153. |
5. | Padhi A, Nain A S. ECM in differentiation: a review of matrix structure, composition and mechanical properties. Ann Biomed Eng, 2020, 48(3): 1071-1089. |
6. | Li J, Liu Y, Zhang Y, et al. Biophysical and biochemical cues of biomaterials guide mesenchymal stem cell behaviors. Front Cell Dev Biol, 2021, 9: 640388. |
7. | Xing H, Lee H, Luo L, et al. Extracellular matrix-derived biomaterials in engineering cell function. Biotechnol Adv, 2020, 42: 107421. |
8. | Ma J, Huang C. Composition and mechanism of three-dimensional hydrogel system in regulating stem cell fate. Tissue Eng Part B Rev, 2020, 26(6): 498-518. |
9. | Deng Z, Jin J, Wang S, et al. Narrative review of the choices of stem cell sources and hydrogels for cartilage tissue engineering. Ann Transl Med, 2020, 8(23): 1598. |
10. | Abdul Halim N A, Hussein M Z, Kandar M K. Nanomaterials-upconverted hydroxyapatite for bone tissue engineering and a platform for drug delivery. Int J Nanomedicine, 2021, 16: 6477-6496. |
11. | 田键, 汤钒, 胡攀, 等. 羟基磷灰石复合及掺杂改性研究进展. 有色金属材料与工程. 2021, 42(4): 55-60. |
12. | Xu J, Zhang J, Shi Y, et al. Surface modification of biomedical Ti and Ti alloys: a review on current advances. Materials (Basel), 2022, 15(5): 1749. |
13. | Halim A, Ariyanti A D, Luo Q, et al. Recent progress in engineering mesenchymal stem cell differentiation. Stem Cell Rev Rep, 2020, 16(4): 661-674. |
14. | Manokawinchoke J, Pavasant P, Limjeerajarus C N, et al. Mechanical loading and the control of stem cell behavior. Arch Oral Biol, 2021, 125: 105092. |
15. | Han Y L, Wang S, Zhang X, et al. Engineering physical microenvironment for stem cell based regenerative medicine. Drug Discov Today, 2014, 19(6): 763-773. |
16. | Huang Y, Qian J Y, Cheng H, et al. Effects of shear stress on differentiation of stem cells into endothelial cells. World J Stem Cells, 2021, 13(7): 894-913. |
17. | Zheng L, Shi Q, Na J, et al. Platelet-derived growth factor receptor-α and β are involved in fluid shear stress regulated cell migration in human periodontal ligament cells. Cell Mol Bioeng, 2019, 12(1): 85-97. |
18. | Shi Q, Zheng L, Na J, et al. Fluid shear stress promotes periodontal ligament cells proliferation via p38-AMOT-YAP. Cell Mol Life Sci. 2022, 79(11):551. |
19. | Cun X, Hosta-Rigau L. Topography: a biophysical approach to direct the fate of mesenchymal stem cells in tissue engineering applications. Nanomaterials, 2020, 10(10): 2070. |
20. | Chen G, Kawazoe N. Regulation of stem cell functions by micro-patterned structures. Adv Exp Med Biol, 2020, 1250: 141-155. |
21. | Kilian K A, Bugarija B, Lahn B T, et al. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci U S A, 2010, 107(11): 4872-4877. |
22. | Tang S W, Yuen W, Kaur I, et al. Capturing instructive cues of tissue microenvironment by silica bioreplication. Acta Biomater, 2020, 102: 114-126. |
23. | Ronaldson-Bouchard K, Teles D, Yeager K, et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nat Biomed Eng, 2022, 6(4): 351-371. |
24. | Wu Y, Ravnic D J, Ozbolat I T. Intraoperative bioprinting: repairing tissues and organs in a surgical setting. Trends Biotechnol, 2020, 38(6): 594-605. |
25. | Turner P R, Murray E, Mcadam C J, et al. Peptide chitosan/dextran core/shell vascularized 3D constructs for wound healing. ACS Appl Mater Interfaces, 2020, 12(29): 32328-32339. |
26. | Yu D, Wang J, Qian K J, et al. Effects of nanofibers on mesenchymal stem cells: environmental factors affecting cell adhesion and osteogenic differentiation and their mechanisms. J Zhejiang Univ Sci B, 2020, 21(11): 871-884. |
27. | Jahanmard F, Baghban E M, Amani M, et al. Incorporation of F-MWCNTs into electrospun nanofibers regulates osteogenesis through stiffness and nanotopography. Mater Sci Eng C Mater Biol Appl, 2020, 106: 110163. |
28. | Kozaniti F K, Deligianni D D, Georgiou M D, et al. The role of substrate topography and stiffness on msc cells functions: key material properties for biomimetic bone tissue engineering. Biomimetics (Basel), 2021, 7(1): 7. |
29. | Wong S W, Lenzini S, Giovanni R, et al. Matrix biophysical cues direct mesenchymal stromal cell functions in immunity. Acta Biomater, 2021, 133: 126-138. |
30. | Chan C E, Odde D J. Traction dynamics of filopodia on compliant substrates. Science, 2008, 322(5908): 1687-1691. |
31. | Wan W, Cheng B, Zhang C, et al. Synergistic effect of matrix stiffness and inflammatory factors on osteogenic differentiation of msc. Biophys J, 2019, 117(1): 129-142. |
32. | Engler A J, Sen S, Sweeney H L, et al. Matrix elasticity directs stem cell lineage specification. Cell, 2006, 126(4): 677-689. |
33. | Kim C, Young J L, Holle A W, et al. Stem cell mechanosensation on gelatin methacryloyl (GelMA) stiffness gradient hydrogels. Ann Biomed Eng, 2020, 48(2): 893-902. |
34. | Oh B, Wu Y-W, Swaminathan V, et al. Modulating the electrical and mechanical microenvironment to guide neuronal stem cell differentiation. Adv Sci (Weinh), 2021, 8(7): 2002112. |
35. | Huebsch N, Lippens E, Lee K, et al. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation. Nat Mater, 2015, 14(12): 1269-1277. |
36. | Dunham C, Havlioglu N, Chamberlain A, et al. Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model. FASEB J, 2020, 34(9): 12976-12990. |
37. | Bae M, Hwang D W, Ko M K, et al. Neural stem cell delivery using brain-derived tissue-specific bioink for recovering from traumatic brain injury. Biofabrication, 2021, 13(4): 044110. |
38. | Morrison D A, Kop A M, Nilasaroya A, et al. Cranial reconstruction using allogeneic mesenchymal stromal cells: a phase 1 first-in-human trial. J Tissue Eng Regen Med, 2018, 12(2): 341-348. |
39. | Vining K H, Stafford A, Mooney D J. Sequential modes of crosslinking tune viscoelasticity of cell-instructive hydrogels. Biomaterials, 2019, 188: 187-197. |
40. | McBeath R, Pirone D M, Nelson C M, et al. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell, 2004, 6(4): 483-495. |
41. | Jiao F, Zhao Y, Sun Q, et al. Spreading area and shape regulate the apoptosis and osteogenesis of mesenchymal stem cells on circular and branched micropatterned islands. J Biomed Mater Res A, 2020, 108(10): 2080-2089. |
42. | Zheng L, Jiang J, Gui J, et al. Influence of micropatterning on human periodontal ligament cells' behavior. Biophys J, 2018, 114(8): 1988-2000. |
43. | Coyer S R, Singh A, Dumbauld D W, et al. Nanopatterning reveals an ECM area threshold for focal adhesion assembly and force transmission that is regulated by integrin activation and cytoskeleton tension. J Cell Sci, 2012, 125(Pt 21): 5110-5123. |
44. | Changede R, Cai H, Wind S J, et al. Integrin nanoclusters can bridge thin matrix fibres to form cell–matrix adhesions. Nat Mater, 2019, 18(12): 1366-1375. |
45. | Pedrosa C R, Chanseau C, Labrugere C, et al. Mesenchymal stem cell differentiation driven by osteoinductive bioactive nanoscale topographies. Appl Sci-Basel, 2021, 11(23):11209. |
46. | Guo N N, Liu L P, Zheng Y W, et al. Inducing human induced pluripotent stem cell differentiation through embryoid bodies: a practical and stable approach. World J Stem Cells, 2020, 12(1): 25-34. |
47. | He X, Wang Q, Zhao Y, et al. Effect of intramyocardial grafting collagen scaffold with mesenchymal stromal cells in patients with chronic ischemic heart disease: a randomized clinical trial. JAMA Netw Open, 2020, 3(9): e2016236. |
48. | Sun Y, Wan B, Wang R, et al. Mechanical stimulation on mesenchymal stem cells and surrounding microenvironments in bone regeneration: regulations and applications. Front Cell Dev Biol, 2022, 10: 808303. |
49. | Zhang R, Wan J, Wang H. Mechanical strain triggers differentiation of dental mesenchymal stem cells by activating osteogenesis-specific biomarkers expression. Am J Transl Res, 2019, 11(1): 233-244. |
50. | Walters B, Turner P A, Rolauffs B, et al. Controlled growth factor delivery and cyclic stretch induces a smooth muscle cell-like phenotype in adipose-derived stem cells. Cells, 2021, 10(11): 3123. |
51. | Yan J, Wang W B, Fan Y J, et al. Cyclic stretch induces vascular smooth muscle cells to secrete connective tissue growth factor and promote endothelial progenitor cell differentiation and angiogenesis. Front Cell Dev Biol, 2020, 8: 606989. |
52. | Jing L, Fan S, Yao X, et al. Effects of compound stimulation of fluid shear stress plus ultrasound on stem cell proliferation and osteogenesis. Regen Biomater, 2021, 8(6): rbab066. |
53. | Sone N, Konishi S, Igura K, et al. Multicellular modeling of ciliopathy by combining iPS cells and microfluidic airway-on-a-chip technology. Sci Transl Med, 2021, 13(601): eabb1298. |
54. | Huang Y, Chen X F, Che J F, et al. Shear stress promotes arterial endothelium-oriented differentiation of mouse-induced pluripotent stem cells. Stem Cells Int, 2019, 2019: 1847098. |
55. | Zheng L, Chen L, Chen Y, et al. The effects of fluid shear stress on proliferation and osteogenesis of human periodontal ligament cells. J Biomech, 2016, 49(4): 572-579. |
56. | 马刘红, 陈莹, 孙晓梅, 等. 下颌骨牵张成骨术后对上颌骨发育长期随访的研究. 中国美容整形外科杂志, 2021, 32(7): 418-421. |
57. | Mogil R J, Kaste S C, Ferry R J, Jr., et al. Effect of low-magnitude, high-frequency mechanical stimulation on BMD among young childhood cancer survivors: a randomized clinical trial. JAMA Oncol, 2016, 2(7): 908-914. |
58. | Veltri A, Lang C, Lien W H. Concise review: Wnt signaling pathways in skin development and epidermal stem cells. Stem Cells, 2018, 36(1): 22-35. |
59. | Sun Y, Yuan Y, Wu W, et al. The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation. Cell Biosci, 2021, 11(1): 88. |
60. | Joshi J, Mahajan G, Kothapalli C R. Three-dimensional collagenous niche and azacytidine selectively promote time-dependent cardiomyogenesis from human bone marrow-derived MSC spheroids. Biotechnol Bioeng, 2018, 115(8): 2013-2026. |
61. | Ronkina N, Gaestel M. Mapk-activated protein kinases: servant or partner?. Annu Rev Biochem, 2022, 91: 505-540. |
62. | Šimoliūnas E, Ivanauskienė I, Bagdzevičiūtė L, et al. Surface stiffness depended gingival mesenchymal stem cell sensitivity to oxidative stress. Free Radic Biol Med, 2021, 169: 62-73. |
63. | Li J, Yan J F, Wan Q Q, et al. Matrix stiffening by self-mineralizable guided bone regeneration. Acta Biomater, 2021, 125: 112-125. |
64. | Cao X, Wang C, Liu J, et al. Regulation and functions of the Hippo pathway in stemness and differentiation. Acta Biochim Biophys Sin (Shanghai), 2020, 52(7): 736-748. |
65. | Yin J Q, Zhu J, Ankrum J A. Manufacturing of primed mesenchymal stromal cells for therapy. Nat Biomed Eng, 2019, 3(2): 90-104. |
- 1. Kimbrel E A, Lanza R. Next-generation stem cells-ushering in a new era of cell-based therapies. Nat Rev Drug Discov, 2020, 19(7): 463-479.
- 2. Abdul-Al M, Kyeremeh G K, Saeinasab M, et al. Stem cell niche microenvironment: review. Bioengineering, 2021, 8(8): 108.
- 3. Hicks M R, Pyle A D. The emergence of the stem cell niche. Trends Cell Biol, 2023, 33(2): 112-123.
- 4. Aaronson S A. Growth factors and cancer. Science, 1991, 254(5035): 1146-1153.
- 5. Padhi A, Nain A S. ECM in differentiation: a review of matrix structure, composition and mechanical properties. Ann Biomed Eng, 2020, 48(3): 1071-1089.
- 6. Li J, Liu Y, Zhang Y, et al. Biophysical and biochemical cues of biomaterials guide mesenchymal stem cell behaviors. Front Cell Dev Biol, 2021, 9: 640388.
- 7. Xing H, Lee H, Luo L, et al. Extracellular matrix-derived biomaterials in engineering cell function. Biotechnol Adv, 2020, 42: 107421.
- 8. Ma J, Huang C. Composition and mechanism of three-dimensional hydrogel system in regulating stem cell fate. Tissue Eng Part B Rev, 2020, 26(6): 498-518.
- 9. Deng Z, Jin J, Wang S, et al. Narrative review of the choices of stem cell sources and hydrogels for cartilage tissue engineering. Ann Transl Med, 2020, 8(23): 1598.
- 10. Abdul Halim N A, Hussein M Z, Kandar M K. Nanomaterials-upconverted hydroxyapatite for bone tissue engineering and a platform for drug delivery. Int J Nanomedicine, 2021, 16: 6477-6496.
- 11. 田键, 汤钒, 胡攀, 等. 羟基磷灰石复合及掺杂改性研究进展. 有色金属材料与工程. 2021, 42(4): 55-60.
- 12. Xu J, Zhang J, Shi Y, et al. Surface modification of biomedical Ti and Ti alloys: a review on current advances. Materials (Basel), 2022, 15(5): 1749.
- 13. Halim A, Ariyanti A D, Luo Q, et al. Recent progress in engineering mesenchymal stem cell differentiation. Stem Cell Rev Rep, 2020, 16(4): 661-674.
- 14. Manokawinchoke J, Pavasant P, Limjeerajarus C N, et al. Mechanical loading and the control of stem cell behavior. Arch Oral Biol, 2021, 125: 105092.
- 15. Han Y L, Wang S, Zhang X, et al. Engineering physical microenvironment for stem cell based regenerative medicine. Drug Discov Today, 2014, 19(6): 763-773.
- 16. Huang Y, Qian J Y, Cheng H, et al. Effects of shear stress on differentiation of stem cells into endothelial cells. World J Stem Cells, 2021, 13(7): 894-913.
- 17. Zheng L, Shi Q, Na J, et al. Platelet-derived growth factor receptor-α and β are involved in fluid shear stress regulated cell migration in human periodontal ligament cells. Cell Mol Bioeng, 2019, 12(1): 85-97.
- 18. Shi Q, Zheng L, Na J, et al. Fluid shear stress promotes periodontal ligament cells proliferation via p38-AMOT-YAP. Cell Mol Life Sci. 2022, 79(11):551.
- 19. Cun X, Hosta-Rigau L. Topography: a biophysical approach to direct the fate of mesenchymal stem cells in tissue engineering applications. Nanomaterials, 2020, 10(10): 2070.
- 20. Chen G, Kawazoe N. Regulation of stem cell functions by micro-patterned structures. Adv Exp Med Biol, 2020, 1250: 141-155.
- 21. Kilian K A, Bugarija B, Lahn B T, et al. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci U S A, 2010, 107(11): 4872-4877.
- 22. Tang S W, Yuen W, Kaur I, et al. Capturing instructive cues of tissue microenvironment by silica bioreplication. Acta Biomater, 2020, 102: 114-126.
- 23. Ronaldson-Bouchard K, Teles D, Yeager K, et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nat Biomed Eng, 2022, 6(4): 351-371.
- 24. Wu Y, Ravnic D J, Ozbolat I T. Intraoperative bioprinting: repairing tissues and organs in a surgical setting. Trends Biotechnol, 2020, 38(6): 594-605.
- 25. Turner P R, Murray E, Mcadam C J, et al. Peptide chitosan/dextran core/shell vascularized 3D constructs for wound healing. ACS Appl Mater Interfaces, 2020, 12(29): 32328-32339.
- 26. Yu D, Wang J, Qian K J, et al. Effects of nanofibers on mesenchymal stem cells: environmental factors affecting cell adhesion and osteogenic differentiation and their mechanisms. J Zhejiang Univ Sci B, 2020, 21(11): 871-884.
- 27. Jahanmard F, Baghban E M, Amani M, et al. Incorporation of F-MWCNTs into electrospun nanofibers regulates osteogenesis through stiffness and nanotopography. Mater Sci Eng C Mater Biol Appl, 2020, 106: 110163.
- 28. Kozaniti F K, Deligianni D D, Georgiou M D, et al. The role of substrate topography and stiffness on msc cells functions: key material properties for biomimetic bone tissue engineering. Biomimetics (Basel), 2021, 7(1): 7.
- 29. Wong S W, Lenzini S, Giovanni R, et al. Matrix biophysical cues direct mesenchymal stromal cell functions in immunity. Acta Biomater, 2021, 133: 126-138.
- 30. Chan C E, Odde D J. Traction dynamics of filopodia on compliant substrates. Science, 2008, 322(5908): 1687-1691.
- 31. Wan W, Cheng B, Zhang C, et al. Synergistic effect of matrix stiffness and inflammatory factors on osteogenic differentiation of msc. Biophys J, 2019, 117(1): 129-142.
- 32. Engler A J, Sen S, Sweeney H L, et al. Matrix elasticity directs stem cell lineage specification. Cell, 2006, 126(4): 677-689.
- 33. Kim C, Young J L, Holle A W, et al. Stem cell mechanosensation on gelatin methacryloyl (GelMA) stiffness gradient hydrogels. Ann Biomed Eng, 2020, 48(2): 893-902.
- 34. Oh B, Wu Y-W, Swaminathan V, et al. Modulating the electrical and mechanical microenvironment to guide neuronal stem cell differentiation. Adv Sci (Weinh), 2021, 8(7): 2002112.
- 35. Huebsch N, Lippens E, Lee K, et al. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation. Nat Mater, 2015, 14(12): 1269-1277.
- 36. Dunham C, Havlioglu N, Chamberlain A, et al. Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model. FASEB J, 2020, 34(9): 12976-12990.
- 37. Bae M, Hwang D W, Ko M K, et al. Neural stem cell delivery using brain-derived tissue-specific bioink for recovering from traumatic brain injury. Biofabrication, 2021, 13(4): 044110.
- 38. Morrison D A, Kop A M, Nilasaroya A, et al. Cranial reconstruction using allogeneic mesenchymal stromal cells: a phase 1 first-in-human trial. J Tissue Eng Regen Med, 2018, 12(2): 341-348.
- 39. Vining K H, Stafford A, Mooney D J. Sequential modes of crosslinking tune viscoelasticity of cell-instructive hydrogels. Biomaterials, 2019, 188: 187-197.
- 40. McBeath R, Pirone D M, Nelson C M, et al. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell, 2004, 6(4): 483-495.
- 41. Jiao F, Zhao Y, Sun Q, et al. Spreading area and shape regulate the apoptosis and osteogenesis of mesenchymal stem cells on circular and branched micropatterned islands. J Biomed Mater Res A, 2020, 108(10): 2080-2089.
- 42. Zheng L, Jiang J, Gui J, et al. Influence of micropatterning on human periodontal ligament cells' behavior. Biophys J, 2018, 114(8): 1988-2000.
- 43. Coyer S R, Singh A, Dumbauld D W, et al. Nanopatterning reveals an ECM area threshold for focal adhesion assembly and force transmission that is regulated by integrin activation and cytoskeleton tension. J Cell Sci, 2012, 125(Pt 21): 5110-5123.
- 44. Changede R, Cai H, Wind S J, et al. Integrin nanoclusters can bridge thin matrix fibres to form cell–matrix adhesions. Nat Mater, 2019, 18(12): 1366-1375.
- 45. Pedrosa C R, Chanseau C, Labrugere C, et al. Mesenchymal stem cell differentiation driven by osteoinductive bioactive nanoscale topographies. Appl Sci-Basel, 2021, 11(23):11209.
- 46. Guo N N, Liu L P, Zheng Y W, et al. Inducing human induced pluripotent stem cell differentiation through embryoid bodies: a practical and stable approach. World J Stem Cells, 2020, 12(1): 25-34.
- 47. He X, Wang Q, Zhao Y, et al. Effect of intramyocardial grafting collagen scaffold with mesenchymal stromal cells in patients with chronic ischemic heart disease: a randomized clinical trial. JAMA Netw Open, 2020, 3(9): e2016236.
- 48. Sun Y, Wan B, Wang R, et al. Mechanical stimulation on mesenchymal stem cells and surrounding microenvironments in bone regeneration: regulations and applications. Front Cell Dev Biol, 2022, 10: 808303.
- 49. Zhang R, Wan J, Wang H. Mechanical strain triggers differentiation of dental mesenchymal stem cells by activating osteogenesis-specific biomarkers expression. Am J Transl Res, 2019, 11(1): 233-244.
- 50. Walters B, Turner P A, Rolauffs B, et al. Controlled growth factor delivery and cyclic stretch induces a smooth muscle cell-like phenotype in adipose-derived stem cells. Cells, 2021, 10(11): 3123.
- 51. Yan J, Wang W B, Fan Y J, et al. Cyclic stretch induces vascular smooth muscle cells to secrete connective tissue growth factor and promote endothelial progenitor cell differentiation and angiogenesis. Front Cell Dev Biol, 2020, 8: 606989.
- 52. Jing L, Fan S, Yao X, et al. Effects of compound stimulation of fluid shear stress plus ultrasound on stem cell proliferation and osteogenesis. Regen Biomater, 2021, 8(6): rbab066.
- 53. Sone N, Konishi S, Igura K, et al. Multicellular modeling of ciliopathy by combining iPS cells and microfluidic airway-on-a-chip technology. Sci Transl Med, 2021, 13(601): eabb1298.
- 54. Huang Y, Chen X F, Che J F, et al. Shear stress promotes arterial endothelium-oriented differentiation of mouse-induced pluripotent stem cells. Stem Cells Int, 2019, 2019: 1847098.
- 55. Zheng L, Chen L, Chen Y, et al. The effects of fluid shear stress on proliferation and osteogenesis of human periodontal ligament cells. J Biomech, 2016, 49(4): 572-579.
- 56. 马刘红, 陈莹, 孙晓梅, 等. 下颌骨牵张成骨术后对上颌骨发育长期随访的研究. 中国美容整形外科杂志, 2021, 32(7): 418-421.
- 57. Mogil R J, Kaste S C, Ferry R J, Jr., et al. Effect of low-magnitude, high-frequency mechanical stimulation on BMD among young childhood cancer survivors: a randomized clinical trial. JAMA Oncol, 2016, 2(7): 908-914.
- 58. Veltri A, Lang C, Lien W H. Concise review: Wnt signaling pathways in skin development and epidermal stem cells. Stem Cells, 2018, 36(1): 22-35.
- 59. Sun Y, Yuan Y, Wu W, et al. The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation. Cell Biosci, 2021, 11(1): 88.
- 60. Joshi J, Mahajan G, Kothapalli C R. Three-dimensional collagenous niche and azacytidine selectively promote time-dependent cardiomyogenesis from human bone marrow-derived MSC spheroids. Biotechnol Bioeng, 2018, 115(8): 2013-2026.
- 61. Ronkina N, Gaestel M. Mapk-activated protein kinases: servant or partner?. Annu Rev Biochem, 2022, 91: 505-540.
- 62. Šimoliūnas E, Ivanauskienė I, Bagdzevičiūtė L, et al. Surface stiffness depended gingival mesenchymal stem cell sensitivity to oxidative stress. Free Radic Biol Med, 2021, 169: 62-73.
- 63. Li J, Yan J F, Wan Q Q, et al. Matrix stiffening by self-mineralizable guided bone regeneration. Acta Biomater, 2021, 125: 112-125.
- 64. Cao X, Wang C, Liu J, et al. Regulation and functions of the Hippo pathway in stemness and differentiation. Acta Biochim Biophys Sin (Shanghai), 2020, 52(7): 736-748.
- 65. Yin J Q, Zhu J, Ankrum J A. Manufacturing of primed mesenchymal stromal cells for therapy. Nat Biomed Eng, 2019, 3(2): 90-104.