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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Review Article

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

Author(s): Alfredo Gorio*, Hongkun Gao, Marco Klinger, Valeriano Vinci and Francesca Paino

Volume 19, Issue 5, 2024

Published on: 19 July, 2023

Page: [688 - 699] Pages: 12

DOI: 10.2174/1574888X18666230605120546

Price: $65

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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.

Keywords: Spinal cord injury, adipose tissue, mechanical activation, cell therapies, inflammation, neuroprotection, neurogenesis.

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[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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1002/1097-4644(20001215)79:4<648:AID-JCB130>3.0.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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1089/scd.2011.0198] [PMID: 21510815]

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