Mechanically Activated Adipose Tissue as a Source for Novel Therapies in Neurological Disease/Injury


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Abstract

In this review, we describe a new avenue that involves the therapeutic use of human adipose tissue. In the past two decades, thousands of papers have described the potential clinical use of human fat and adipose tissue. Moreover, mesenchymal stem cells have been a source of great enthusiasm in clinical studies, and these have generated curiosity at academic levels. On the other hand, they have created considerable commercial business opportunities. High expectations have emerged for curing some recalcitrant diseases or reconstructing anatomically defective human body parts, but several concerns have been raised by generating criticism on the clinical practice that have not been substantiated by rigorous scientific evidence. However, in general, the consensus is that human adipose-derived mesenchymal stem cells inhibit the production of inflammatory cytokines and stimulate the production of anti-inflammatory cytokines. Here, we show that the application of a mechanical elliptical force for several minutes to human abdominal fat activates anti-inflammatory properties and gene-related expression. This may pave the way for new unexpected clinical developments.

About the authors

Alfredo Gorio

, University of Milan Medical School,

Author for correspondence.
Email: info@benthamscience.net

Hongkun Gao

, Tongren Hospital,

Email: info@benthamscience.net

Marco Klinger

, Istituto Clinico Humanitas

Email: info@benthamscience.net

Valeriano Vinci

, Istituto Clinico Humanita

Email: info@benthamscience.net

Francesca Paino

Department of Biomedical, Surgical and Dental Sciences - CRC StaMeTec, University of Milan

Email: info@benthamscience.net

References

  1. Xu P, Yang X. The efficacy and safety of mesenchymal stem cell transplantation for spinal cord injury patients: A meta-analysis and systematic review. Cell Transplant 2019; 28(1): 36-46. doi: 10.1177/0963689718808471 PMID: 30362373
  2. Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine Phila Pa 1976 2001; (26): S2-S12.
  3. Fehlings MG, Cadotte DW, Fehlings LN. A series of systematic reviews on the treatment of acute spinal cord injury: A foundation for best medical practice. J Neurotrauma 2011; 28(8): 1329-33. doi: 10.1089/neu.2011.1955 PMID: 21651382
  4. Carelli S, Colli M, Vinci V, Caviggioli F, Klinger M, Gorio A. Mechanical activation of adipose tissue and derived mesenchymal stem cells: Novel anti-inflammatory properties. Int J Mol Sci 2018; 19(1): 267. doi: 10.3390/ijms19010267 PMID: 29337886
  5. Dyer DP, Salanga CL, Johns SC, et al. The anti-inflammatory protein TSG-6 regulates chemokine function by inhibiting chemokine/glycosaminoglycan interactions. J Biol Chem 2016; 291(24): 12627-40. doi: 10.1074/jbc.M116.720953 PMID: 27044744
  6. Benveniste EN. Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am J Physiol 1992; 263(1 Pt 1): C1-C16. PMID: 1636671
  7. Taoka Y, Okajima K. Spinal cord injury in the rat. Prog Neurobiol 1998; 56(3): 341-58. doi: 10.1016/S0301-0082(98)00049-5 PMID: 9770243
  8. Cheng Z, Bosco DB, Sun L, et al. Neural stem cell-conditioned medium suppresses inflammation and promotes spinal cord injury recovery. Cell Transplant 2017; 26(3): 469-82. doi: 10.3727/096368916X693473 PMID: 27737726
  9. Zhou L, Ouyang L, Lin S, et al. Protective role of β-carotene against oxidative stress and neuroinflammation in a rat model of spinal cord injury. Int Immunopharmacol 2018; 61: 92-9. doi: 10.1016/j.intimp.2018.05.022 PMID: 29857242
  10. Cinti S, Mitchell G, Barbatelli G, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46(11): 2347-55. doi: 10.1194/jlr.M500294-JLR200 PMID: 16150820
  11. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7. doi: 10.1126/science.284.5411.143 PMID: 10102814
  12. Carelli S, Giallongo T, Gombalova Z, Merli D, Di Giulio AM, Gorio A. EPO-releasing neural precursor cells promote axonal regeneration and recovery of function in spinal cord traumatic injury. Restor Neurol Neurosci 2017; 35(6): 583-99. doi: 10.3233/RNN-170750 PMID: 29172009
  13. Carelli S, Giallongo T, Gerace C, et al. Neural stem cell transplantation in experimental contusive model of spinal cord injury. J Vis Exp 2014; 94(94): 52141. PMID: 25548937
  14. Carelli S, Giallongo T, Marfia G, et al. Exogenous adult postmortem neural precursors attenuate secondary degeneration and promote myelin sparing and functional recovery following experimental spinal cord injury. Cell Transplant 2015; 24(4): 703-19. doi: 10.3727/096368914X685140 PMID: 25299753
  15. Gorio A, Gokmen N, Erbayraktar S, et al. Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci 2002; 99(14): 9450-5. doi: 10.1073/pnas.142287899 PMID: 12082184
  16. Gorio A, Madaschi L, Di Stefano B, et al. Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury. Proc Natl Acad Sci 2005; 102(45): 16379-84. doi: 10.1073/pnas.0508479102 PMID: 16260722
  17. Costa DD, Beghi E, Carignano P, et al. Tolerability and efficacy of erythropoietin (EPO) treatment in traumatic spinal cord injury: A preliminary randomized comparative trial vs. methylprednisolone (MP). Neurol Sci 2015; 36(9): 1567-74. doi: 10.1007/s10072-015-2182-5 PMID: 25820146
  18. Basso DM, Fisher LC, Anderson AJ, Jakeman LB, Mctigue DM, Popovich PG. Basso mouse scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. J Neurotrauma 2006; 23(5): 635-59. doi: 10.1089/neu.2006.23.635 PMID: 16689667
  19. Carelli S, Giallongo T, Rey F, et al. Neuroprotection, recovery of function and endogenous neurogenesis in traumatic spinal cord injury following transplantation of activated adipose tissue. Cells 2019; 8(4): 329. doi: 10.3390/cells8040329 PMID: 30965679
  20. Kostura MJ, Tocci MJ, Limjuco G, et al. Identification of a monocyte specific pre-interleukin 1 β convertase activity. Proc Natl Acad Sci 1989; 86(14): 5227-31. doi: 10.1073/pnas.86.14.5227 PMID: 2787508
  21. Carelli S, Giallongo T, Viaggi C, et al. Recovery from experimental parkinsonism by intrastriatal application of erythropoietin or EPO-releasing neural precursors. Neuropharmacology 2017; 119: 76-90. doi: 10.1016/j.neuropharm.2017.03.035 PMID: 28373075
  22. Curtis E, Martin JR, Gabel B, et al. A first-in-human, phase I study of neural stem cell transplantation for chronic spinal cord injury. Cell Stem Cell 2018; 22(6): 941-950.e6. doi: 10.1016/j.stem.2018.05.014 PMID: 29859175
  23. Donovan J, Kirshblum S. Clinical trials in traumatic spinal cord injury. Neurotherapeutics 2018; 15(3): 654-68. doi: 10.1007/s13311-018-0632-5 PMID: 29736858
  24. Saberi H, Firouzi M, Habibi Z, et al. Safety of intramedullary schwann cell transplantation for postrehabilitation spinal cord injuries: 2-year follow-up of 33 cases. J Neurosurg Spine 2011; 15(5): 515-25. doi: 10.3171/2011.6.SPINE10917 PMID: 21800956
  25. Betz VM, Sitoci-Ficici KH, Uckermann O, et al. Gene-activated fat grafts for the repair of spinal cord injury: A pilot study. Acta Neurochir 2016; 158(2): 367-78. doi: 10.1007/s00701-015-2626-y PMID: 26592254
  26. Zhu H, Poon W, Liu Y, et al. Phase I-II clinical trial assessing safety and efficacy of umbilical cord blood mononuclear cell transplant therapy of chronic complete spinal cord injury. Cell Transplant 2016; 25(11): 1925-43. doi: 10.3727/096368916X691411 PMID: 27075659
  27. Manack A, Motsko SP, Haag-Molkenteller C, et al. Epidemiology and healthcare utilization of neurogenic bladder patients in a us claims database. Neurourol Urodyn 2011; 30(3): 395-401. doi: 10.1002/nau.21003 PMID: 20882676
  28. Al Taweel W, Seyam R. Neurogenic bladder in spinal cord injury patients. Res Rep Urol 2015; 7: 85-99. doi: 10.2147/RRU.S29644 PMID: 26090342
  29. Pruitt BL, Dunn AR, Weis WI, Nelson WJ. Mechano-transduction: from molecules to tissues. PLoS Biol 2014; 12(11): e1001996. doi: 10.1371/journal.pbio.1001996 PMID: 25405923
  30. El Haj AJ, Walker LM, Preston MR, Publicover SJ. Mechanotransduction pathways in bone: Calcium fluxes and the role of voltage-operated calcium channels. Med Biol Eng Comput 1999; 37(3): 403-9. doi: 10.1007/BF02513320 PMID: 10505395
  31. Na S, Collin O, Chowdhury F, et al. Rapid signal transduction in living cells is a unique feature of mechanotransduction. Proc Natl Acad Sci 2008; 105(18): 6626-31. doi: 10.1073/pnas.0711704105 PMID: 18456839
  32. Walker LM, Publicover SJ, Preston MR, Said Ahmed MAA, El Haj AJ. Calcium-channel activation and matrix protein upregulation in bone cells in response to mechanical strain. J Cell Biochem 2000; 79(4): 648-61. doi: 10.1002/1097-4644(20001215)79:43.0.CO;2-Q PMID: 10996855
  33. Iyer KV, Pulford S, Mogilner A, Shivashankar GV. Mechanical activation of cells induces chromatin remodeling preceding MKL nuclear transport. Biophys J 2012; 103(7): 1416-28. doi: 10.1016/j.bpj.2012.08.041 PMID: 23062334
  34. Chen LJ, Wei SY, Chiu JJ. Mechanical regulation of epigenetics in vascular biology and pathobiology. J Cell Mol Med 2013; 17(4): 437-48. doi: 10.1111/jcmm.12031 PMID: 23551392
  35. European Medicines Agency, 2019. Available from: ww.ema.europa.eu (Accessed on: 1 January 2019).
  36. U.S. Food & Drug Administration, 2019. Available from: www.fda.gov (Accessed on; 1 January 2019).
  37. Hyun I, Lindvall O, Ährlund-Richter L, et al. New ISSCR guidelines underscore major principles for responsible translational stem cell research. Cell Stem Cell 2008; 3(6): 607-9. doi: 10.1016/j.stem.2008.11.009 PMID: 19041777
  38. Bourin P, Bunnell BA, Casteilla L, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 2013; 15(6): 641-8. doi: 10.1016/j.jcyt.2013.02.006 PMID: 23570660
  39. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-7. doi: 10.1080/14653240600855905 PMID: 16923606
  40. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001; 7(2): 211-28. doi: 10.1089/107632701300062859 PMID: 11304456
  41. Gimble JM, Bunnell BA, Chiu ES, Guilak F. Taking stem cells beyond discovery: A milestone in the reporting of regulatory requirements for cell therapy. Stem Cells Dev 2011; 20(8): 1295-6. doi: 10.1089/scd.2011.0198 PMID: 21510815

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