Stem cells sheets for bone and cartilage repair_West China Medical Journal

Authors：

MA Hong ¹ , XING Fei ¹ , XIANG Zhou ¹ ,  DUAN Xin ^1,2,3

1. Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Orthopedics, Gerontological Hospital of Sichuan Province, the Fifth People’s Hospital of Sichuan Province, Chengdu, Sichuan 610041, P. R. China;
3. Department of Orthopedics, Ganzi Tibetan Autonomous Prefecture People’s Hospital, Ganzi, Sichuan 626000, P. R. China;

Corresponding author：

DUAN Xin, Email: dxbaal@hotmail.com

Keywords：

Mesenchymal stem cells; cell sheets; bone repair; cartilage repair; tissue engineering

DOI：

10.7507/1002-0179.202204071

Video：

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Abstract Full text Figures/Tables Video References Cited by

Cell sheet technology refers to the preparation of cells into thin sheets, which retains a large amount of extracellular matrix, cell-cell junctions, and has a wide range of applications in the repair and regeneration of osteochondral tissues. This paper discusses the types, properties, and construction methods of stem cell sheets, and reviews the current research status of vascularization of stem cell sheets and their composite application with various cytokines and scaffolding materials for bone and cartilage repair, with the aim of exploring the direction of the further development of stem cell sheets in the field of bone and cartilage.

Citation： MA Hong, XING Fei, XIANG Zhou, DUAN Xin. Stem cells sheets for bone and cartilage repair. West China Medical Journal, 2023, 38(10): 1553-1558. doi: 10.7507/1002-0179.202204071 Copy

1.	Nakao M, Inanaga D, Nagase K, et al. Characteristic differences of cell sheets composed of mesenchymal stem cells with different tissue origins. Regen Ther, 2019, 11: 34-40.
2.	Kim SR, Yi HJ, Lee YN, et al. Engineered mesenchymal stem-cell-sheets patches prevents postoperative pancreatic leakage in a rat model. Sci Rep, 2018, 8(1): 360.
3.	Shin MJ, Shim IK, Kim DM, et al. Engineered cell sheets for the effective delivery of adipose-derived stem cells for tendon-to-bone healing. Am J Sports Med, 2020, 48(13): 3347-3358.
4.	Li H, Huang J, Wang Y, et al. Nanoscale modification of titanium implants improves behaviors of bone mesenchymal stem cells and osteogenesis in vivo. Oxid Med Cell Longev, 2022, 2022: 2235335.
5.	Chen M, Xu Y, Zhang T, et al. Mesenchymal stem cell sheets: a new cell-based strategy for bone repair and regeneration. Biotechnol Lett, 2019, 41(3): 305-318.
6.	Zhang Y, Lei Z, Qi Y, et al. Adipose-derived stem cell sheet encapsulated construct of micro-porous decellularized cartilage debris and hydrogel for cartilage defect repair. Med Hypotheses, 2017, 109: 111-113.
7.	Yamada N, Okano T, Sakai H, et al. Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells. Die Macromol Chem Rapid Commun, 2003, 11: 571-576.
8.	Choi A, Yoon H, Han SJ, et al. Rapid harvesting of stem cell sheets by thermoresponsive bulk poly(N-isopropylacrylamide) (PNIPAAm) nanotopography. Biomater Sci, 2020, 8(19): 5260-5270.
9.	Weng Y, Wang Z, Sun J, et al. Engineering of axially vascularized bone tissue using natural coral scaffold and osteogenic bone marrow mesenchymal stem cell sheets. J Stomatol Oral Maxillofac Surg, 2021, 122(4): 397-404.
10.	Silva AS, Santos LF, Mendes MC, et al. Multi-layer pre-vascularized magnetic cell sheets for bone regeneration. Biomaterials, 2020, 231: 119664.
11.	Hong Y, Yu M, Weng W, et al. Light-induced cell detachment for cell sheet technology. Biomaterials, 2013, 34(1): 11-18.
12.	Jiang Z, Zhu D, Yu K, et al. Recent advances in light-induced cell sheet technology. Acta Biomater, 2021, 119: 30-41.
13.	Cheng Z, Cheng K, Weng W. SiO₂/TiO₂ Nanocomposite films on polystyrene for light-induced cell detachment application. ACS Appl Mater Interfaces, 2017, 9(3): 2130-2137.
14.	Tang Y, Chen C, Liu F, et al. Structure and ingredient-based biomimetic scaffolds combining with autologous bone marrow-derived mesenchymal stem cell sheets for bone-tendon healing. Biomaterials, 2020, 241: 119837.
15.	Nakao M, Kim K, Nagase K, et al. Phenotypic traits of mesenchymal stem cell sheets fabricated by temperature-responsive cell culture plate: structural characteristics of MSC sheets. Stem Cell Res Ther, 2019, 10(1): 353.
16.	Wei X, Wang L, Duan C, et al. Cardiac patches made of brown adipose-derived stem cell sheets and conductive electrospun nanofibers restore infarcted heart for ischemic myocardial infarction. Bioact Mater, 2023, 27: 271-287.
17.	Nakano K, Murata K, Omokawa S, et al. Promotion of osteogenesis and angiogenesis in vascularized tissue-engineered bone using osteogenic matrix cell sheets. Plast Reconstr Surg, 2016, 137(5): 1476-1484.
18.	Fujii Y, Kawase-Koga Y, Hojo H, et al. Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology. Stem Cell Res Ther, 2018, 9(1): 24.
19.	Yoshida Y, Matsubara H, Fang X, et al. Adipose-derived stem cell sheets accelerate bone healing in rat femoral defects. PLoS One, 2019, 14(3): e0214488.
20.	Liu Y, Wang H, Dou H, et al. Bone regeneration capacities of alveolar bone mesenchymal stem cells sheet in rabbit calvarial bone defect. J Tissue Eng, 2020, 11: 2041731420930379.
21.	Kim Y, Kang BJ, Kim WH, et al. Evaluation of mesenchymal stem cell sheets overexpressing BMP-7 in canine critical-sized bone defects. Int J Mol Sci, 2018, 19(7): 2073.
22.	Wang Z, Wu G, Wei M, et al. Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection. Int J Nanomedicine, 2016, 11: 2091-105.
23.	Zhang W, Hou W, Chen M, et al. Upregulation of Parkin accelerates osteoblastic differentiation of bone marrow-derived mesenchymal stem cells and bone regeneration by enhancing autophagy and β-catenin signaling. Front Cell Dev Biol, 2020, 8: 576104.
24.	Dang PN, Herberg S, Varghai D, et al. Endochondral ossification in critical-sized bone defects via readily implantable scaffold-free stem cell constructs. Stem Cells Transl Med, 2017, 6(7): 1644-1659.
25.	Zhang Y, Wang P, Wang Y, et al. Gold nanoparticles promote the bone regeneration of periodontal ligament stem cell sheets through activation of autophagy. Int J Nanomedicine, 2021, 16: 61-73.
26.	He Y, Li Y, Chen G, et al. Concentration-dependent cellular behavior and osteogenic differentiation effect induced in bone marrow mesenchymal stem cells treated with magnetic graphene oxide. J Biomed Mater Res A, 2020, 108(1): 50-60.
27.	Tian Y, Xu Y, Xue T, et al. Notch activation enhances mesenchymal stem cell sheet osteogenic potential by inhibition of cellular senescence. Cell Death Dis, 2017, 8(2): e2595.
28.	Liu H, Jiao Y, Zhou W, et al. Endothelial progenitor cells improve the therapeutic effect of mesenchymal stem cell sheets on irradiated bone defect repair in a rat model. J Transl Med, 2018, 16(1): 137.
29.	Zhang H, Zhou Y, Yu N, et al. Construction of vascularized tissue-engineered bone with polylysine-modified coral hydroxyapatite and a double cell-sheet complex to repair a large radius bone defect in rabbits. Acta Biomater, 2019, 91: 82-98.
30.	Wang Z, Han L, Sun T, et al. Osteogenic and angiogenic lineage differentiated adipose-derived stem cells for bone regeneration of calvarial defects in rabbits. J Biomed Mater Res A, 2021, 109(4): 538-550.
31.	Wu P, Zhang X, Hu Y, et al. Co-culture with endothelial progenitor cells promotes the osteogenesis of bone mesenchymal stem cells via the VEGF-YAP axis in high-glucose environments. Int J Med Sci, 2021, 18(7): 1628-1638.
32.	Lin J, Shao J, Juan L, et al. Enhancing bone regeneration by combining mesenchymal stem cell sheets with β-TCP/COL-I scaffolds. J Biomed Mater Res B Appl Biomater, 2018, 106(5): 2037-2045.
33.	Shan X, Hu D. Bone engineering by cell sheet technology to repair mandibular defects. Exp Ther Med, 2017, 14(5): 5007-5011.
34.	Xue D, Zhang W, Chen E, et al. Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing. Oncotarget, 2017, 8(26): 42098-42115.
35.	Zhang D, Gao P, Li Q, et al. Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats. Stem Cell Res Ther, 2017, 8(1): 134.
36.	Wang X, Li G, Guo J, et al. Hybrid composites of mesenchymal stem cell sheets, hydroxyapatite, and platelet-rich fibrin granules for bone regeneration in a rabbit calvarial critical-size defect model. Exp Ther Med, 2017, 13(5): 1891-1899.
37.	Ma N, Wang H, Xu X, et al. Autologous-cell-derived, tissue-engineered cartilage for repairing articular cartilage lesions in the knee: study protocol for a randomized controlled trial. Trials, 2017, 18(1): 519.
38.	Armiento AR, Alini M, Stoddart MJ. Articular fibrocartilage - why does hyaline cartilage fail to repair?. Adv Drug Deliv Rev, 2019, 146: 289-305.
39.	Takatori N, Sato M, Toyoda E, et al. Cartilage repair and inhibition of the progression of cartilage degeneration after transplantation of allogeneic chondrocyte sheets in a nontraumatic early arthritis model. Regen Ther, 2018, 9: 24-31.
40.	Karlsen TA, Shahdadfar A, Brinchmann JE. Human primary articular chondrocytes, chondroblasts-like cells, and dedifferentiated chondrocytes: differences in gene, microRNA, and protein expression and phenotype. Tissue Eng Part C Methods, 2011, 17(2): 219-227.
41.	Thorp H, Kim K, Kondo M, et al. Fabrication of hyaline-like cartilage constructs using mesenchymal stem cell sheets. Sci Rep, 2020, 10(1): 20869.
42.	Le TM, Vu NB, Huynh PD, et al. Treatment of osteochondral femoral head defect by human umbilical cord mesenchymal stem cell sheet transplantation: an experimental study in rats. Adv Exp Med Biol, 2021: 6.
43.	You Q, Liu Z, Zhang J, et al. Human amniotic mesenchymal stem cell sheets encapsulating cartilage particles facilitate repair of rabbit osteochondral defects. Am J Sports Med, 2020, 48(3): 599-611.
44.	Thorp H, Kim K, Bou-Ghannam S, et al. Enhancing chondrogenic potential via mesenchymal stem cell sheet multilayering. Regen Ther, 2021, 18: 487-496.
45.	Jia S, Wang J, Zhang T, et al. Multilayered scaffold with a compact interfacial layer enhances osteochondral defect repair. ACS Appl Mater Interfaces, 2018, 10(24): 20296-20305.
46.	Chen T, Bai J, Tian J, et al. A single integrated osteochondral in situ composite scaffold with a multi-layered functional structure. Colloids Surf B Biointerfaces, 2018, 167: 354-363.
47.	Jin L, Zhao W, Ren B, et al. Osteochondral tissue regenerated via a strategy by stacking pre-differentiated BMSC sheet on fibrous mesh in a gradient. Biomed Mater, 2019, 14(6): 065017.
48.	Wang RM, Johnson TD, He J, et al. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials. Biomaterials, 2017, 129: 98-110.
49.	Wang Z, Han L, Sun T, et al. Extracellular matrix derived from allogenic decellularized bone marrow mesenchymal stem cell sheets for the reconstruction of osteochondral defects in rabbits. Acta Biomater, 2020, 118: 54-68.
50.	Zhang Y, Feng G, Xu G, et al. Microporous acellular extracellular matrix combined with adipose-derived stem cell sheets as a promising tissue patch promoting articular cartilage regeneration and interface integration. Cytotherapy, 2019, 21(8): 856-869.

1. Nakao M, Inanaga D, Nagase K, et al. Characteristic differences of cell sheets composed of mesenchymal stem cells with different tissue origins. Regen Ther, 2019, 11: 34-40.
2. Kim SR, Yi HJ, Lee YN, et al. Engineered mesenchymal stem-cell-sheets patches prevents postoperative pancreatic leakage in a rat model. Sci Rep, 2018, 8(1): 360.
3. Shin MJ, Shim IK, Kim DM, et al. Engineered cell sheets for the effective delivery of adipose-derived stem cells for tendon-to-bone healing. Am J Sports Med, 2020, 48(13): 3347-3358.
4. Li H, Huang J, Wang Y, et al. Nanoscale modification of titanium implants improves behaviors of bone mesenchymal stem cells and osteogenesis in vivo. Oxid Med Cell Longev, 2022, 2022: 2235335.
5. Chen M, Xu Y, Zhang T, et al. Mesenchymal stem cell sheets: a new cell-based strategy for bone repair and regeneration. Biotechnol Lett, 2019, 41(3): 305-318.
6. Zhang Y, Lei Z, Qi Y, et al. Adipose-derived stem cell sheet encapsulated construct of micro-porous decellularized cartilage debris and hydrogel for cartilage defect repair. Med Hypotheses, 2017, 109: 111-113.
7. Yamada N, Okano T, Sakai H, et al. Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells. Die Macromol Chem Rapid Commun, 2003, 11: 571-576.
8. Choi A, Yoon H, Han SJ, et al. Rapid harvesting of stem cell sheets by thermoresponsive bulk poly(N-isopropylacrylamide) (PNIPAAm) nanotopography. Biomater Sci, 2020, 8(19): 5260-5270.
9. Weng Y, Wang Z, Sun J, et al. Engineering of axially vascularized bone tissue using natural coral scaffold and osteogenic bone marrow mesenchymal stem cell sheets. J Stomatol Oral Maxillofac Surg, 2021, 122(4): 397-404.
10. Silva AS, Santos LF, Mendes MC, et al. Multi-layer pre-vascularized magnetic cell sheets for bone regeneration. Biomaterials, 2020, 231: 119664.
11. Hong Y, Yu M, Weng W, et al. Light-induced cell detachment for cell sheet technology. Biomaterials, 2013, 34(1): 11-18.
12. Jiang Z, Zhu D, Yu K, et al. Recent advances in light-induced cell sheet technology. Acta Biomater, 2021, 119: 30-41.
13. Cheng Z, Cheng K, Weng W. SiO₂/TiO₂ Nanocomposite films on polystyrene for light-induced cell detachment application. ACS Appl Mater Interfaces, 2017, 9(3): 2130-2137.
14. Tang Y, Chen C, Liu F, et al. Structure and ingredient-based biomimetic scaffolds combining with autologous bone marrow-derived mesenchymal stem cell sheets for bone-tendon healing. Biomaterials, 2020, 241: 119837.
15. Nakao M, Kim K, Nagase K, et al. Phenotypic traits of mesenchymal stem cell sheets fabricated by temperature-responsive cell culture plate: structural characteristics of MSC sheets. Stem Cell Res Ther, 2019, 10(1): 353.
16. Wei X, Wang L, Duan C, et al. Cardiac patches made of brown adipose-derived stem cell sheets and conductive electrospun nanofibers restore infarcted heart for ischemic myocardial infarction. Bioact Mater, 2023, 27: 271-287.
17. Nakano K, Murata K, Omokawa S, et al. Promotion of osteogenesis and angiogenesis in vascularized tissue-engineered bone using osteogenic matrix cell sheets. Plast Reconstr Surg, 2016, 137(5): 1476-1484.
18. Fujii Y, Kawase-Koga Y, Hojo H, et al. Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology. Stem Cell Res Ther, 2018, 9(1): 24.
19. Yoshida Y, Matsubara H, Fang X, et al. Adipose-derived stem cell sheets accelerate bone healing in rat femoral defects. PLoS One, 2019, 14(3): e0214488.
20. Liu Y, Wang H, Dou H, et al. Bone regeneration capacities of alveolar bone mesenchymal stem cells sheet in rabbit calvarial bone defect. J Tissue Eng, 2020, 11: 2041731420930379.
21. Kim Y, Kang BJ, Kim WH, et al. Evaluation of mesenchymal stem cell sheets overexpressing BMP-7 in canine critical-sized bone defects. Int J Mol Sci, 2018, 19(7): 2073.
22. Wang Z, Wu G, Wei M, et al. Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection. Int J Nanomedicine, 2016, 11: 2091-105.
23. Zhang W, Hou W, Chen M, et al. Upregulation of Parkin accelerates osteoblastic differentiation of bone marrow-derived mesenchymal stem cells and bone regeneration by enhancing autophagy and β-catenin signaling. Front Cell Dev Biol, 2020, 8: 576104.
24. Dang PN, Herberg S, Varghai D, et al. Endochondral ossification in critical-sized bone defects via readily implantable scaffold-free stem cell constructs. Stem Cells Transl Med, 2017, 6(7): 1644-1659.
25. Zhang Y, Wang P, Wang Y, et al. Gold nanoparticles promote the bone regeneration of periodontal ligament stem cell sheets through activation of autophagy. Int J Nanomedicine, 2021, 16: 61-73.
26. He Y, Li Y, Chen G, et al. Concentration-dependent cellular behavior and osteogenic differentiation effect induced in bone marrow mesenchymal stem cells treated with magnetic graphene oxide. J Biomed Mater Res A, 2020, 108(1): 50-60.
27. Tian Y, Xu Y, Xue T, et al. Notch activation enhances mesenchymal stem cell sheet osteogenic potential by inhibition of cellular senescence. Cell Death Dis, 2017, 8(2): e2595.
28. Liu H, Jiao Y, Zhou W, et al. Endothelial progenitor cells improve the therapeutic effect of mesenchymal stem cell sheets on irradiated bone defect repair in a rat model. J Transl Med, 2018, 16(1): 137.
29. Zhang H, Zhou Y, Yu N, et al. Construction of vascularized tissue-engineered bone with polylysine-modified coral hydroxyapatite and a double cell-sheet complex to repair a large radius bone defect in rabbits. Acta Biomater, 2019, 91: 82-98.
30. Wang Z, Han L, Sun T, et al. Osteogenic and angiogenic lineage differentiated adipose-derived stem cells for bone regeneration of calvarial defects in rabbits. J Biomed Mater Res A, 2021, 109(4): 538-550.
31. Wu P, Zhang X, Hu Y, et al. Co-culture with endothelial progenitor cells promotes the osteogenesis of bone mesenchymal stem cells via the VEGF-YAP axis in high-glucose environments. Int J Med Sci, 2021, 18(7): 1628-1638.
32. Lin J, Shao J, Juan L, et al. Enhancing bone regeneration by combining mesenchymal stem cell sheets with β-TCP/COL-I scaffolds. J Biomed Mater Res B Appl Biomater, 2018, 106(5): 2037-2045.
33. Shan X, Hu D. Bone engineering by cell sheet technology to repair mandibular defects. Exp Ther Med, 2017, 14(5): 5007-5011.
34. Xue D, Zhang W, Chen E, et al. Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing. Oncotarget, 2017, 8(26): 42098-42115.
35. Zhang D, Gao P, Li Q, et al. Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats. Stem Cell Res Ther, 2017, 8(1): 134.
36. Wang X, Li G, Guo J, et al. Hybrid composites of mesenchymal stem cell sheets, hydroxyapatite, and platelet-rich fibrin granules for bone regeneration in a rabbit calvarial critical-size defect model. Exp Ther Med, 2017, 13(5): 1891-1899.
37. Ma N, Wang H, Xu X, et al. Autologous-cell-derived, tissue-engineered cartilage for repairing articular cartilage lesions in the knee: study protocol for a randomized controlled trial. Trials, 2017, 18(1): 519.
38. Armiento AR, Alini M, Stoddart MJ. Articular fibrocartilage - why does hyaline cartilage fail to repair?. Adv Drug Deliv Rev, 2019, 146: 289-305.
39. Takatori N, Sato M, Toyoda E, et al. Cartilage repair and inhibition of the progression of cartilage degeneration after transplantation of allogeneic chondrocyte sheets in a nontraumatic early arthritis model. Regen Ther, 2018, 9: 24-31.
40. Karlsen TA, Shahdadfar A, Brinchmann JE. Human primary articular chondrocytes, chondroblasts-like cells, and dedifferentiated chondrocytes: differences in gene, microRNA, and protein expression and phenotype. Tissue Eng Part C Methods, 2011, 17(2): 219-227.
41. Thorp H, Kim K, Kondo M, et al. Fabrication of hyaline-like cartilage constructs using mesenchymal stem cell sheets. Sci Rep, 2020, 10(1): 20869.
42. Le TM, Vu NB, Huynh PD, et al. Treatment of osteochondral femoral head defect by human umbilical cord mesenchymal stem cell sheet transplantation: an experimental study in rats. Adv Exp Med Biol, 2021: 6.
43. You Q, Liu Z, Zhang J, et al. Human amniotic mesenchymal stem cell sheets encapsulating cartilage particles facilitate repair of rabbit osteochondral defects. Am J Sports Med, 2020, 48(3): 599-611.
44. Thorp H, Kim K, Bou-Ghannam S, et al. Enhancing chondrogenic potential via mesenchymal stem cell sheet multilayering. Regen Ther, 2021, 18: 487-496.
45. Jia S, Wang J, Zhang T, et al. Multilayered scaffold with a compact interfacial layer enhances osteochondral defect repair. ACS Appl Mater Interfaces, 2018, 10(24): 20296-20305.
46. Chen T, Bai J, Tian J, et al. A single integrated osteochondral in situ composite scaffold with a multi-layered functional structure. Colloids Surf B Biointerfaces, 2018, 167: 354-363.
47. Jin L, Zhao W, Ren B, et al. Osteochondral tissue regenerated via a strategy by stacking pre-differentiated BMSC sheet on fibrous mesh in a gradient. Biomed Mater, 2019, 14(6): 065017.
48. Wang RM, Johnson TD, He J, et al. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials. Biomaterials, 2017, 129: 98-110.
49. Wang Z, Han L, Sun T, et al. Extracellular matrix derived from allogenic decellularized bone marrow mesenchymal stem cell sheets for the reconstruction of osteochondral defects in rabbits. Acta Biomater, 2020, 118: 54-68.
50. Zhang Y, Feng G, Xu G, et al. Microporous acellular extracellular matrix combined with adipose-derived stem cell sheets as a promising tissue patch promoting articular cartilage regeneration and interface integration. Cytotherapy, 2019, 21(8): 856-869.

West China Medical Journal

Stem cells sheets for bone and cartilage repair

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