Different Protocols of Combined Application of Photobiomodulation In Vitro and In Vivo Plus AdiposeDerived Stem Cells Improve the Healing of Bones in Critical Size Defects in Rat Models Photobiomodulation Plus Stem Cells Improve Bone Healing
Journal of Lasers in Medical Sciences,
Vol. 13 (2022),
Introduction: Long bone segmental deficiencies are challenging complications to treat. Hereby, the effects of the scaffold derived from the human demineralized bone matrix (hDBMS) plus human adipose stem cells (hADSs) plus photobiomodulation (PBM) (in vitro and or in vivo) on the catabolic step of femoral bone repair in rats with critical size femoral defects (CDFDs) were evaluated with stereology and high stress load (HSL) assessment methods.
Methods: hADSs were exposed to PBM in vitro; then, the mixed influences of hDBMS+hADS+PBM on CSFDs were evaluated. CSFDs were made on both femurs; then hDBMSs were engrafted into both CSFDs of all rats. There were 6 groups (G)s: G1 was the control; in G2 (hADS), hADSs only were engrafted into hDBMS of CSFD; in G3 (PBM) only PBM therapy for CSFD was provided; in G4 (hADS+PBM in vivo), seeded hADSs on hDBMS of CSFDs were radiated with a laser in vivo; in G5 (hADSs+PBM under in vitro condition), hADSs in a culture system were radiated with a laser, then transferred on hDBMS of CSFDs; and in G6 (hADS+PBM in conditions of in vivo and in vitro), laser-exposed hADSs were transplanted on hDBMS of CSFDs, and then CSFDs were exposed to a
laser in vivo.
Results: Groups 4, 5, and 6 meaningfully improved HSLs of CSFD in comparison with groups 3, 1, and 2 (all, P=0.001). HSL of G5 was significantly more than G4 and G6 (both, P=0.000). Gs 6 and 4 significantly increased new bone volumes of CSFD compared to Gs 2 (all, P=0.000) and 1 (P=0.001 & P=0.003 respectively). HSL of G 1 was significantly lower than G5 (P=0.026).
Conclusion: HSLs of CSFD in rats that received treatments of hDBMS plus hADS plus PBM were significantly higher than treatments with hADS and PBM alone and in control groups.
- critical size bone defect, fracture healing, demineralized bone scaffold, human adipose-derived stem cell, photobiomodulation
How to Cite
2. Amin S, Achenbach SJ, Atkinson EJ, Khosla S, Melton LJ, 3rd. Trends in fracture incidence: a population-based study over 20 years. J Bone Miner Res. 2014;29(3):581-9. doi: 10.1002/jbmr.2072.
3. Calori G, Albisetti W, Agus A, Iori S, Tagliabue L. Risk factors contributing to fracture non-unions. Injury. 2007;38:S11-S8. doi: 10.1016/s0020-1383(07)80004-0.
4. Schlickewei CW, Kleinertz H, Thiesen DM, Mader K, Priemel M, Frosch K-H, et al. Current and Future Concepts for the Treatment of Impaired Fracture Healing. Int. J. Mol. Sci; 2019, 20(22), 5805; https://doi.org/10.3390/ijms20225805
5. Toosi S, Behravan N, Behravan J. Nonunion fractures, mesenchymal stem cells and bone tissue engineering. J Biomed Mater Res A. 2018;106(9):2552-62. DOI: 10.1002/jbm.a.36433
6. Giannoudis PV, Dinopoulos HT. Autologous bone graft: when shall we add growth factors? Foot Ank Clin. 2010;15(4):597-609. DOI: 10.1016/j.fcl.2010.09.005
7. Manjila SV, Mroz T, Steinmetz MP. Lumbar Interbody Fusions E-Book: Elsevier Health Sciences; 2018.
8. Huang Y-Z, Cai J-Q, Xue J, Chen X-H, Zhang C-L, Li X-Q, et al. The poor osteoinductive capability of human acellular bone matrix. The Int j Artif organs. 2012;35(12):1061-9. DOI: 10.5301/ijao.5000122
9. Ramis JM, Calvo J, Matas A, Corbillo C, Gayà A, Monjo M. Enhanced osteoinductive capacity and decreased variability by enrichment of demineralized bone matrix with a bone protein extract. J Mater Sci Mater Med. 2018;29(7):103. DOI: 10.1007/s10856-018-6115-8
10. Watanabe Y, Harada N, Sato K, Abe S, Yamanaka K, Matushita T. Stem cell therapy: is there a future for reconstruction of large bone defects? Injury. 2016;47 Suppl 1:S47-51. DOI: 10.1016/S0020-1383(16)30012-2
11. Storti G, Scioli MG, Kim B-S, Orlandi A, Cervelli V. Adipose-derived stem cells in bone tissue engineering: Useful tools with new applications. Stem cells int. 2019 Nov 6;2019:3673857.doi: 10.1155/2019/3673857.
12. Dozza B, Salamanna F, Baleani M, Giavaresi G, Parrilli A, Zani L, et al. Nonunion fracture healing: Evaluation of effectiveness of demineralized bone matrix and mesenchymal stem cells in a novel sheep bone nonunion model. J Tissue Eng Regen Med. 2018;12(9):1972-85. DOI: 10.1002/term.2732
13. Mott A, Mitchell A, McDaid C, Harden M, Grupping R, Dean A, et al. Systematic review assessing the evidence for the use of stem cells in fracture healing. Bone Jt Open. 2020 Oct 6;1(10):628-638. doi: 10.1302/2633-1462.110.BJO-2020-0129.
14. Ebrahimi T, Moslemi N, Rokn A, Heidari M, Nokhbatolfoghahaie H, Fekrazad R. The influence of low-intensity laser therapy on bone healing. J Dent (Tehran, Iran). Fall 2012;9(4):238-48.
Epub 2012 Dec 31. PMCID: PMC3536459
15. Zare F, Moradi A, Fallahnezhad S, Ghoreishi SK, Amini A, Chien S, et al. Photobiomodulation with 630 plus 810 nm wavelengths induce more in vitro cell viability of human adipose stem cells than human bone marrow-derived stem cells. J Photochem Photobiol B . 2019 Dec;201:111658.doi: 10.1016/j.jphotobiol.2019.111658.
16. Khosravipour A, Amini A, Masteri Farahani R, Zare F, Mostafavinia A, Fallahnezhad S, et al. Preconditioning adipose-derived stem cells with photobiomodulation significantly increased bone healing in a critical size femoral defect in rats. Biochem Biophys Res Commun. 2020;531(2):105-11. 2020 Oct 15;531(2):105-111.doi: 10.1016/j.bbrc.2020.07.048.
17. Mostafavinia A, Razavi S, Abdollahifar M, Amini A, Ghorishi SK, Rezaei F, et al. Evaluation of the effects of photobiomodulation on bone healing in healthy and streptozotocin-induced diabetes in rats. Photomed Laser Surg. 2017;35(10):537-45. DOI: 10.1089/pho.2016.4224
18. Muhammad G, Xu J, Bulte JW, Jablonska A, Walczak P, Janowski M. Transplanted adipose-derived stem cells can be short-lived yet accelerate healing of acid-burn skin wounds: a multimodal imaging study. Sci Rep. 2017 Jul 5;7(1):4644.doi: 10.1038/s41598-017-04484-0.
19. Asgari M, Gazor R, Abdollahifar MA, Fadaei Fathabady F, Zare F, Norouzian M, et al. Combined therapy of adipose-derived stem cells and photobiomodulation on accelerated bone healing of a critical size defect in an osteoporotic rat model. Biochem Biophys Res Commun. 2020 Sep 10;530(1):173-180. doi: 10.1016/j.bbrc.2020.06.023.
20. Claes L, Cunningham J. Monitoring the mechanical properties of healing bone. Clin Orthop Relat Res. 2009 Aug;467(8):1964-71. doi: 10.1007/s11999-009-0752-7
21. Wang X, Li G, Guo J, Yang L, Liu Y, Sun Q, 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):1891-9. DOI: 10.3892/etm.2017.4199
22. Zhou Y, Chen F, Ho ST, Woodruff MA, Lim TM, Hutmacher DW. Combined marrow stromal cell-sheet techniques and high-strength biodegradable composite scaffolds for engineered functional bone grafts. Biomaterials. 2007 Feb;28(5):814-24.doi: 10.1016/j.biomaterials.2006.09.032. Epub 2006 Oct 11.
23. Grayson WL, Bunnell BA, Martin E, Frazier T, Hung BP, Gimble JM. Stromal cells and stem cells in clinical bone regeneration. Nat Rev Endocrinol. 2015 Mar;11(3):140-50.doi: 10.1038/nrendo.2014.234
24. Martino MM, Briquez PS, Güç E, Tortelli F, Kilarski WW, Metzger S, et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science. 2014 Feb 21;343(6173):885-8. doi: 10.1126/science.1247663.
25. Abdi J, Rashedi I, Keating A. Concise Review: TLR pathway‐miRNA interplay in mesenchymal stromal cells: regulatory roles and therapeutic directions. Stem cells. 2018 Nov;36(11):1655-1662. doi: 10.1002/stem.2902. Epub 2018 Oct 13.
26. Baldari S, Di Rocco G, Piccoli M, Pozzobon M, Muraca M, Toietta G. Challenges and Strategies for Improving the Regenerative Effects of Mesenchymal Stromal Cell-Based Therapies. Int J Mol Sci. 2017 Oct 2;18(10):2087. doi: 10.3390/ijms18102087.
27. Torres-Espín A, Redondo-Castro E, Hernandez J, Navarro X. Immunosuppression of allogenic mesenchymal stem cells transplantation after spinal cord injury improves graft survival and beneficial outcomes. J Neurotrauma. 2015 Mar 15;32(6):367-80.doi: 10.1089/neu.2014.3562. Epub 2015 Jan 22
28. Hadjiargyrou M, O'Keefe RJ. The convergence of fracture repair and stem cells: interplay of genes, aging, environmental factors and disease. J bone miner res. 2014 Nov;29(11):2307-22. doi: 10.1002/jbmr.2373.
29. Lee S, Choi E, Cha M-J, Hwang K-C. Cell adhesion and long-term survival of transplanted mesenchymal stem cells: a prerequisite for cell therapy. Oxid med cell longev. 2015;2015:632902.doi: 10.1155/2015/632902. Epub 2015 Feb 2.
30. Fisher JN, Peretti GM, Scotti C. Stem cells for bone regeneration: from cell-based therapies to decellularised engineered extracellular matrices. Stem cells int 2016;2016:9352598. doi: 10.1155/2016/9352598. Epub 2016 Feb 21.
31. Kushibiki T, Hirasawa T, Okawa S, Ishihara M. Low reactive level laser therapy for mesenchymal stromal cells therapies. Stem cells int. 2015;2015:974864.doi: 10.1155/2015/974864. Epub 2015 Jul 26.
32. Wang Y-H, Wu J-Y, Kong SC, Chiang M-H, Ho M-L, Yeh M-L, et al. Low power laser irradiation and human adipose-derived stem cell treatments promote bone regeneration in critical-sized calvarial defects in rats. PLoS One. 2018 Apr 5;13(4):e0195337. doi: 10.1371/journal.pone.0195337. eCollection 2018..
33. Li R, Atesok K, Nauth A, Wright D, Qamirani E, Whyne CM, et al. Endothelial progenitor cells for fracture healing: a microcomputed tomography and biomechanical analysis. J orthop trauma. 2011 Aug;25(8):467-71. doi: 10.1097/BOT.0b013e31821ad4ec.
34. Yao W, Lay YAE, Kot A, Liu R, Zhang H, Chen H, et al. Improved mobilization of exogenous mesenchymal stem cells to bone for fracture healing and sex difference. Stem Cells. 2016 Oct;34(10):2587-2600. doi: 10.1002/stem.2433. Epub 2016 Jul 15.
- Abstract Viewed: 268 times
- PDF Downloaded: 206 times