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Cited by 152Extracellular vesicles in diseaseMesenchymal stem cell researchBone Tissue Engineering Materials

Mesenchymal stem cell exosomes in bone regenerative strategies—a systematic review of preclinical studies

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Tan, S.H.S., Wong, J.R.Y., Sim, S.J.Y., Tjio, C.K.E., Wong, K.L., Chew, J.R.J., Hui, J.H.P., Toh, W.S.·2020·Materials Today Bio
DOI 10.1016/j.mtbio.2020.100067PMC PMC7364174
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Abstract

The ability of bone for regeneration has long been recognized. However, once beyond a critical size, spontaneous regeneration of bone is limited. Several studies have focused on enhancing bone regeneration by applying mesenchymal stromal/stem cells (MSCs) in the treatment strategies. Despite the therapeutic efficacy of MSCs in bone regeneration, cell-based therapies are impeded by several challenges in maintaining the optimal cell potency and viability during expansion, storage, and final delivery to patients. Recently, there has been a paradigm shift in therapeutic mechanism of MSCs in tissue repair from one based on cellular differentiation and replacement to one based on secretion and paracrine signaling. Among the broad spectrum of trophic factors, extracellular vesicles ​particularly the exosomes have been reported to be therapeutically efficacious in several injury/disease indications, including bone defects and diseases. The current systematic review aims to summarize the results of the existing animal studies which were conducted to evaluate the therapeutic efficacy of MSC exosomes for bone regeneration. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis ​guidelines, the PubMed and The Cochrane Library database were searched for relevant controlled preclinical animal studies. A total of 23 studies were identified, with the total sample size being 690 rats or mice and 38 rabbits. Generally, MSC exosomes were found to be efficacious for bone regeneration in animal models of bone defects and diseases such as osteonecrosis and osteoporosis. In these studies, MSC exosomes promoted new bone formation with supporting vasculature ​and displayed improved morphological, biomechanical, and histological outcomes, coupled with positive effects on cell survival, proliferation, and migration, osteogenesis, and angiogenesis. Unclear-to-low risk in bias and incomplete reporting in the primary studies highlighted the need for standardization in outcome measurements and reporting. Further studies in large animal models to establish the safety and efficacy would provide useful information on guiding the design of clinical trials.

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  • Secreted exosomes dominate the beneficial effects of implanted MSCs on bone reconstruction.

    “A growing body of evidence indicates that the secreted exosomes dominate the beneficial effects of implanted MSCs on bone reconstruction [16,17].”

    From Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation (2025) · cites this paper as [16]

    The Introduction says MSC exosomes have shown efficacy in bone regeneration, and the Discussion describes several ways they may promote it. Neither passage establishes that exosomes dominate the beneficial effects of implanted MSCs; the review notes that their therapeutic mechanisms remain incompletely understood. No page numbers are available in our copy. (LLM, conf=0.86)

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  1. [1]Galen The usefulness of parts of the body Clin. Orthop. Relat. Res. 1997 3 12 9137171
  2. [2]Dimitriou R. Tsiridis E. Giannoudis P.V. Current concepts of molecular aspects of bone healing Injury 36 2005 1392 1404 16102764
  3. [3]Grabowski P. Physiology of bone Endocr. Dev. 28 2015 33 55 26138834
  4. [4]Walmsley G.G. Ransom R.C. Zielins E.R. Leavitt T. Flacco J.S. Hu M.S. Lee A.S. Longaker M.T. Wan D.C. Stem cells in bone regeneration Stem Cell Rev. Rep. 12 2016 524 529 27250635 PMC5053855
  5. [5]US Preventive Services Task Force Curry S.J. Krist A.H. Owens D.K. Barry M.J. Caughey A.B. Davidson K.W. Doubeni C.A. Epling J.W. Jr. Kemper A.R. Kubik M. Landefeld C.S. Mangione C.M. Phipps M.G. Pignone M. Silverstein M. Simon M.A. Tseng C.W. Wong J.B. Screening for osteoporosis to prevent fractures: US preventive services task force recommendation statement J. Am. Med. Assoc. 319 2018 2521 2531 29946735
  6. [6]Ekegren C.L. Edwards E.R. de Steiger R. Gabbe B.J. Incidence, costs and predictors of non-union, delayed union and mal-union following long bone fracture Int. J. Environ. Res. Publ. Health 15 2018 2845 PMC6313538 30551632
  7. [7]Johnson A.J. Mont M.A. Tsao A.K. Jones L.C. Treatment of femoral head osteonecrosis in the United States: 16-year analysis of the Nationwide Inpatient Sample Clin. Orthop. Relat. Res. 472 2014 617 623 23943529 PMC3890194
  8. [8]Simpson A.H.R.W. Robiati L. Jalal M.M.K. Tsang S.T.J. Non-union: indications for external fixation Injury 50 Suppl 1 2019 S73 S78 30955871
  9. [9]Birch J.G. A brief history of limb lengthening J. Pediatr. Orthop. 37 Suppl 2 2017 S1 S8 28799987
  10. [10]Bhandari M. Swiontkowski M. Management of acute hip fracture N. Engl. J. Med. 377 2017 2053 2062 29166235
  11. [11]Hernlund E. Svedbom A. Ivergård M. Compston J. Cooper C. Stenmark J. McCloskey E.V. Jönsson B. Kanis J.A. Osteoporosis in the European union: medical management, epidemiology and economic burden. A report prepared in collaboration with the international osteoporosis foundation (IOF) and the European federation of pharmaceutical industry associations (EFPIA) Arch. Osteoporos. 8 2013 136 24113837 PMC3880487
  12. [12]Hak D.J. Fitzpatrick D. Bishop J.A. Marsh J.L. Tilp S. Schnettler R. Simpson H. Alt V. Delayed union and nonunions: epidemiology, clinical issues, and financial aspects Injury 45 Suppl 2 2014 S3 S7 24857025
  13. [13]Greenwald A.S. Boden S.D. Goldberg V.M. Khan Y. Laurencin C.T. Rosier R.N. American Academy of Orthopaedic Surgeons The committee on biological implants, bone-graft substitutes: facts, fictions, and applications J. Bone Jt. Surg. Am. 83-A Suppl 2 Pt 2 2001 98 103 11712842
  14. [14]Baldwin P. Li D.J. Auston D.A. Mir H.S. Yoon R.S. Koval K.J. Autograft, allograft, and bone graft substitutes: clinical evidence and indications for use in the setting of orthopaedic trauma surgery J. Orthop. Trauma 33 2019 203 213 30633080
  15. [15]Finkemeier C.G. Bone-grafting and bone-graft substitutes J. Bone Jt. Surg. Am. 84 2002 454 464 11886919
  16. [16]Sohn H.S. Oh J.K. Review of bone graft and bone substitutes with an emphasis on fracture surgeries Biomater. Res. 23 2019 9 30915231 PMC6417250
  17. [17]Galipeau J. Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities Cell Stem Cell 22 2018 824 833 29859173 PMC6434696
  18. [18]Hernigou P. Auregan J.C. Dubory A. Flouzat-Lachaniette C.H. Chevallier N. Rouard H. Subchondral stem cell therapy versus contralateral total knee arthroplasty for osteoarthritis following secondary osteonecrosis of the knee Int. Orthop. 42 2018 2563 2571 29589086
  19. [19]Hernigou P. Dubory A. Homma Y. Guissou I. Flouzat Lachaniette C.H. Chevallier N. Rouard H. Cell therapy versus simultaneous contralateral decompression in symptomatic corticosteroid osteonecrosis: a thirty year follow-up prospective randomized study of one hundred and twenty five adult patients Int. Orthop. 42 2018 1639 1649 29744647
  20. [20]Chen C. Qu Z. Yin X. Shang C. Ao Q. Gu Y. Liu Y. Efficacy of umbilical cord-derived mesenchymal stem cell-based therapy for osteonecrosis of the femoral head: a three-year follow-up study Mol. Med. Rep. 14 2016 4209 4215 27634376 PMC5101965
  21. [21]Liebergall M. Schroeder J. Mosheiff R. Gazit Z. Yoram Z. Rasooly L. Daskal A. Khoury A. Weil Y. Beyth S. Stem cell-based therapy for prevention of delayed fracture union: a randomized and prospective preliminary study Mol. Ther. 21 2013 1631 1638 23732992 PMC3739419
  22. [22]Castillo-Cardiel G. López-Echaury A.C. Saucedo-Ortiz J.A. Fuentes-Orozco C. Michel-Espinoza L.R. Irusteta-Jiménez L. Salazar-Parra M. González-Ojeda A. Bone regeneration in mandibular fractures after the application of autologous mesenchymal stem cells, a randomized clinical trial Dent. Traumatol. 33 2017 38 44 27513920
  23. [23]Tan S.S.H. Tjio C.K.E. Wong J.R.Y. Wong K.L. Chew J.R.J. Hui J.H.P. Toh W.S. Mesenchymal stem cell exosomes for cartilage regeneration: a systematic review of preclinical in vivo studies Tissue Eng. B Rev. 2020 10.1089/ten.TEB.2019.0326 32159464 · DOI
  24. [24]Meirelles L. da S. da Silva Meirelles L. Fontes A.M. Covas D.T. Caplan A.I. Mechanisms involved in the therapeutic properties of mesenchymal stem cells Cytokine Growth Factor Rev. 20 2009 419 427 19926330
  25. [25]Hofer H.R. Tuan R.S. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies Stem Cell Res. Ther. 7 2016 131 27612948 PMC5016979
  26. [26]Zaw S.Y.M. Kaneko T. Zaw Z.C.T. Sone P.P. Murano H. Gu B. Okada Y. Han P. Katsube K.I. Okiji T. Crosstalk between dental pulp stem cells and endothelial cells augments angiogenic factor expression Oral Dis. 2020 10.1111/odi.13341 32248596 · DOI
  27. [27]Xu J. Wang B. Sun Y. Wu T. Liu Y. Zhang J. Lee W.Y. Pan X. Chai Y. Li G. Human fetal mesenchymal stem cell secretome enhances bone consolidation in distraction osteogenesis Stem Cell Res. Ther. 7 2016 134 27612565 PMC5018171
  28. [28]Toh W.S. Lai R.C. Zhang B. Lim S.K. MSC exosome works through a protein-based mechanism of action Biochem. Soc. Trans. 46 2018 843 853 29986939 PMC6103455
  29. [29]Lai R.C. Arslan F. Lee M.M. Sze N.S.K. Choo A. Chen T.S. Salto-Tellez M. Timmers L. Lee C.N. El Oakley R.M. Pasterkamp G. de Kleijn D.P.V. Lim S.K. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury Stem Cell Res. 4 2010 214 222 20138817
  30. [30]Tan C.Y. Lai R.C. Wong W. Dan Y.Y. Lim S.K. Ho H.K. Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models Stem Cell Res. Ther. 5 2014 76 24915963 PMC4229780
  31. [31]Yu B. Shao H. Su C. Jiang Y. Chen X. Bai L. Zhang Y. Li Q. Zhang X. Li X. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1 Sci. Rep. 6 2016 34562 27686625 PMC5043341
  32. [32]Lee C. Mitsialis S.A. Aslam M. Vitali S.H. Vergadi E. Konstantinou G. Sdrimas K. Fernandez-Gonzalez A. Kourembanas S. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension Circulation 126 2012 2601 2611 23114789 PMC3979353
  33. [33]Zhang B. Yeo R.W.Y. Lai R.C. Sim E.W.K. Chin K.C. Lim S.K. Mesenchymal stromal cell exosome-enhanced regulatory T-cell production through an antigen-presenting cell-mediated pathway Cytotherapy 20 2018 687 696 29622483
  34. [34]Zhang B. Yin Y. Lai R.C. Tan S.S. Choo A.B.H. Lim S.K. Mesenchymal stem cells secrete immunologically active exosomes Stem Cell. Dev. 23 2014 1233 1244 24367916
  35. [35]Nakamura Y. Miyaki S. Ishitobi H. Matsuyama S. Nakasa T. Kamei N. Akimoto T. Higashi Y. Ochi M. Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration FEBS Lett. 589 2015 1257 1265 25862500
  36. [36]Bier P. Berenstein Kronfeld N. Morgoulis D. Ziv-Av A. Goldstein H. Kazimirsky G. Cazacu S. Meir R. Popovtzer R. Dori A. Brodie C. Placenta-derived mesenchymal stromal cells and their exosomes exert therapeutic effects in Duchenne muscular dystrophy Biomaterials 174 2018 67 78 29783118
  37. [37]Wong K.L. Zhang S. Wang M. Ren X. Afizah H. Lai R.C. Lim S.K. Lee E.H. Hui J.H.P. Toh W.S. Intra-articular injections of mesenchymal stem cell exosomes and hyaluronic acid improve structural and mechanical properties of repaired cartilage in a rabbit model Arthroscopy 2020 10.1016/j.arthro.2020.03.031 32302651 · DOI
  38. [38]Zhang S. Teo K.Y.W. Chuah S.J. Lai R.C. Lim S.K. Toh W.S. MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis Biomaterials 200 2019 35 47 30771585
  39. [39]Zhang S. Chuah S.J. Lai R.C. Hui J.H.P. Lim S.K. Toh W.S. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity Biomaterials 156 2018 16 27 29182933
  40. [40]Zhang S. Chu W.C. Lai R.C. Lim S.K. Hui J.H.P. Toh W.S. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration Osteoarthritis Cartilage 24 2016 2135 2140 27390028
  41. [41]Chen S. Tang Y. Liu Y. Zhang P. Lv L. Zhang X. Jia L. Zhou Y. Exosomes derived from miR-375-overexpressing human adipose mesenchymal stem cells promote bone regeneration Cell Prolif 52 2019 e12669 PMC6797519 31380594
  42. [43]Guo S.C. Tao S.C. Yin W.J. Qi X. Sheng J.G. Zhang C.Q. Exosomes from human synovial-derived mesenchymal stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head in the rat Int. J. Biol. Sci. 12 2016 1262 1272 27766040 PMC5069447
  43. [44]Jia Y. Qiu S. Xu J. Kang Q. Chai Y. Exosomes secreted by young mesenchymal stem cells promote new bone formation during distraction osteogenesis in older rats Calcif. Tissue Int. 106 2020 509 517 32103287
  44. [45]Kuang M.J. Huang Y. Zhao X.G. Zhang R. Ma J.X. Wang D.C. Ma X.L. Exosomes derived from Wharton's jelly of human umbilical cord mesenchymal stem cells reduce osteocyte apoptosis in glucocorticoid-induced osteonecrosis of the femoral head in rats via the miR-21-PTEN-AKT signalling pathway Int. J. Biol. Sci. 15 2019 1861 1871 31523188 PMC6743291
  45. [46]Li H. Liu D. Li C. Zhou S. Tian D. Xiao D. Zhang H. Gao F. Huang J. Exosomes secreted from mutant-HIF-1α-modified bone-marrow-derived mesenchymal stem cells attenuate early steroid-induced avascular necrosis of femoral head in rabbit Cell Biol. Int. 41 2017 1379 1390 28877384
  46. [47]Li W. Liu Y. Zhang P. Tang Y. Zhou M. Jiang W. Zhang X. Wu G. Zhou Y. Tissue-engineered bone immobilized with human adipose stem cells-derived exosomes promotes bone regeneration ACS Appl. Mater. Interfaces 10 2018 5240 5254 29359912
  47. [48]Li R. Chen C. Zheng R.Q. Zou L. Hao G.L. Zhang G.C. Influences of hucMSC-exosomes on VEGF and BMP-2 expression in SNFH rats Eur. Rev. Med. Pharmacol. Sci. 23 2019 2935 2943 31002144
  48. [49]Li X. Zheng Y. Hou L. Zhou Z. Huang Y. Zhang Y. Jia L. Li W. Exosomes derived from maxillary BMSCs enhanced the osteogenesis in iliac BMSCs Oral Dis. 26 2020 131 144 31541596
  49. [50]Liang B. Liang J.M. Ding J.N. Xu J. Xu J.G. Chai Y.M. Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway Stem Cell Res. Ther. 10 2019 335 31747933 PMC6869275
  50. [51]Liao W. Ning Y. Xu H.J. Zou W.Z. Hu J. Liu X.Z. Yang Y. Li Z.H. BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head Clin. Sci. 133 2019 1955 1975 31387936
  51. [52]Liu X. Li Q. Niu X. Hu B. Chen S. Song W. Ding J. Zhang C. Wang Y. Exosomes secreted from human-induced pluripotent stem cell-derived mesenchymal stem cells prevent osteonecrosis of the femoral head by promoting angiogenesis Int. J. Biol. Sci. 13 2017 232 244 28255275 PMC5332877
  52. [53]Liu W. Li L. Rong Y. Qian D. Chen J. Zhou Z. Luo Y. Jiang D. Cheng L. Zhao S. Kong F. Wang J. Zhou Z. Xu T. Gong F. Huang Y. Gu C. Zhao X. Bai J. Wang F. Zhao W. Zhang L. Li X. Yin G. Fan J. Cai W. Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126 Acta Biomater. 103 2020 196 212 31857259
  53. [54]Qi X. Zhang J. Yuan H. Xu Z. Li Q. Niu X. Hu B. Wang Y. Li X. Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats Int. J. Biol. Sci. 12 2016 836 849 27313497 PMC4910602
  54. [56]Xu H.J. Liao W. Liu X.Z. Hu J. Zou W.Z. Ning Y. Yang Y. Li Z.H. Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head Faseb. J. 33 2019 8055 8068 30964699
  55. [57]Xu T. Luo Y. Wang J. Zhang N. Gu C. Li L. Qian D. Cai W. Fan J. Yin G. Exosomal miRNA-128-3p from mesenchymal stem cells of aged rats regulates osteogenesis and bone fracture healing by targeting Smad5 J. Nanobiotechnol. 18 2020 47 PMC7077029 32178675
  56. [58]Yang B.C. Kuang M.J. Kang J.Y. Zhao J. Ma J.X. Ma X.L. Human umbilical cord mesenchymal stem cell-derived exosomes act via the miR-1263/Mob1/Hippo signaling pathway to prevent apoptosis in disuse osteoporosis Biochem. Biophys. Res. Commun. 524 2020 883 889 32057365
  57. [59]Zhang J. Liu X. Li H. Chen C. Hu B. Niu X. Li Q. Zhao B. Xie Z. Wang Y. Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway Stem Cell Res. Ther. 7 2016 136 27650895 PMC5028974
  58. [60]Zhang Y. Hao Z. Wang P. Xia Y. Wu J. Xia D. Fang S. Xu S. Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1α-mediated promotion of angiogenesis in a rat model of stabilized fracture Cell Prolif 52 2019 e12570 PMC6496165 30663158
  59. [61]Zhang L. Jiao G. Ren S. Zhang X. Li C. Wu W. Wang H. Liu H. Zhou H. Chen Y. Exosomes from bone marrow mesenchymal stem cells enhance fracture healing through the promotion of osteogenesis and angiogenesis in a rat model of nonunion Stem Cell Res. Ther. 11 2020 38 31992369 PMC6986095
  60. [62]Zhou J. Liu H.X. Li S.H. Gong Y.S. Zhou M.W. Zhang J.H. Zhu G.Y. Effects of human umbilical cord mesenchymal stem cells-derived exosomes on fracture healing in rats through the Wnt signaling pathway Eur. Rev. Med. Pharmacol. Sci. 23 2019 4954 4960 31210331
  61. [63]Zuo R. Liu M. Wang Y. Li J. Wang W. Wu J. Sun C. Li B. Wang Z. Lan W. Zhang C. Shi C. Zhou Y. BM-MSC-derived exosomes alleviate radiation-induced bone loss by restoring the function of recipient BM-MSCs and activating Wnt/β-catenin signaling Stem Cell Res. Ther. 10 2019 30 30646958 PMC6334443
  62. [65]Witwer K.W. Van Balkom B.W.M. Bruno S. Choo A. Dominici M. Gimona M. Hill A.F. De Kleijn D. Koh M. Lai R.C. Mitsialis S.A. Ortiz L.A. Rohde E. Asada T. Toh W.S. Weiss D.J. Zheng L. Giebel B. Lim S.K. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications J. Extracell. Vesicles 8 2019 1609206 31069028 PMC6493293
  63. [67]Lai R.C. Tan S.S. Teh B.J. Sze S.K. Arslan F. de Kleijn D.P. Choo A. Lim S.K. Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome Int. J. Proteomics. 2012 2012 971907 22852084 PMC3407643
  64. [68]Toh W.S. Lai R.C. Hui J.H.P. Lim S.K. MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment Semin. Cell Dev. Biol. 67 2017 56 64 27871993
  65. [69]Chen T.S. Lai R.C. Lee M.M. Choo A.B. Lee C.N. Lim S.K. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs Nucleic Acids Res. 38 2010 215 224 19850715 PMC2800221
  66. [70]Silvestro S. Chiricosta L. Gugliandolo A. Pizzicannella J. Diomede F. Bramanti P. Trubiani O. Mazzon E. Extracellular vesicles derived from human gingival mesenchymal stem cells: a transcriptomic analysis Genes 11 2020 118 PMC7073771 31973135
  67. [71]Angulski A.B. Capriglione L.G. Batista M. Marcon B.H. Senegaglia A.C. Stimamiglio M.A. Correa A. The protein content of extracellular vesicles derived from expanded human umbilical cord blood-derived CD133+ and human bone marrow-derived mesenchymal stem cells partially explains why both sources are advantageous for regenerative medicine Stem Cell Rev. Rep. 13 2017 244 257 28054239
  68. [72]Eirin A. Zhu X.Y. Puranik A.S. Woollard J.R. Tang H. Dasari S. Lerman A. van Wijnen A.J. Lerman L.O. Integrated transcriptomic and proteomic analysis of the molecular cargo of extracellular vesicles derived from porcine adipose tissue-derived mesenchymal stem cells PLoS One 12 2017 e0174303 PMC5363917 28333993
  69. [73]Toh W.S. Zhang B. Lai R.C. Lim S.K. Immune regulatory targets of mesenchymal stromal cell exosomes/small extracellular vesicles in tissue regeneration Cytotherapy 20 2018 1419 1426 30352735
  70. [74]Kilkenny C. Browne W. Cuthill I.C. Emerson M. Altman D.G. National centre for the replacement, refinement and reduction of animals in research, animal research: reporting in vivo experiments--the ARRIVE guidelines J. Cerebr. Blood Flow Metabol. 31 2011 991 993 PMC3070981 21206507

Authors
Tan, S. H. S., Wong, J. R. Y., Sim, S. J. Y., Tjio, C. K. E., Wong, K. L., Chew, J. R. J., Hui, J. H. P., & Toh, W. S.
Affiliations
  • National University Health System (SG)
  • SingHealth (SG)
  • National University of Singapore (SG)
Corresponding author
Toh, W.S.
ORCID
Venue
Materials Today Bio
Publisher
Elsevier BV
Published
2020-06
Volume
7
Pages
100067
ISSN
2590-0064 (ISSN-L)
DOI
10.1016/j.mtbio.2020.100067
PMC
PMC7364174
OpenAlex
W3037251899
Cited by
152
References
76
Citations by year
2026: 12 · 2025: 20 · 2024: 33 · 2023: 22 · 2022: 31 · 2021: 24 · 2020: 9 · 2017: 1
FWCI
2.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Materials Today Bio (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Medical Research Council
  • National University of Singapore
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
Keywords
mesenchymal stem cell-derived exosomes, bone regeneration, extracellular vesicles, paracrine signaling, bone defects, avascular necrosis, osteoporosis, angiogenesis, bone formation, preclinical animal models

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