Journal Home > Volume 7 , Issue 2

Stem cell therapy is a promising treatment for neurogenerative disease as well as inflammatory and immune mediated diseases. Decades of preclinical research has demonstrated stem cell ability to differentiate into multiple cell lineages and be utilised in regeneration and repair with their immunomodulatory and immunosuppressive properties. This work has provided the fundamental scientific knowledge needed to launch various clinical trials studying stem cell therapy in autoimmune disorders, stroke, and other tissue injury. Despite the early success many of these promising therapies are yet to breakthrough into clinical use. In this review, we highlight the recent developments in the use of stem cells as therapeutic agents for neurological conditions as well as their failures and how the clinical translation can be improved.


menu
Abstract
Full text
Outline
About this article

Potential of adipose derived stem cell preparations in neurological repair and regeneration

Show Author's information Laura Combes1( )Xenia Sawkulycz1( )Wen-Hui Fang2Baoqiang Guo1Mark Slevin1( )
Department of Life Sciences, Manchester Metropolitan University, Manchester, UK
Department of Biological and Geographical Sciences University of Huddersfield, Huddersfield, UK

Abstract

Stem cell therapy is a promising treatment for neurogenerative disease as well as inflammatory and immune mediated diseases. Decades of preclinical research has demonstrated stem cell ability to differentiate into multiple cell lineages and be utilised in regeneration and repair with their immunomodulatory and immunosuppressive properties. This work has provided the fundamental scientific knowledge needed to launch various clinical trials studying stem cell therapy in autoimmune disorders, stroke, and other tissue injury. Despite the early success many of these promising therapies are yet to breakthrough into clinical use. In this review, we highlight the recent developments in the use of stem cells as therapeutic agents for neurological conditions as well as their failures and how the clinical translation can be improved.

Keywords: Adipose derived mesenchymal stem cells, Micro-fragmented adipose tissue, Suicide gene therapy

References(45)

Aboody KS, Najbauer J, Metz MZ, D'Apuzzo M, Gutova M, Annala AJ, Synold TW, Couture LA, Blanchard S, Moats RA, Garcia E, Aramburo S, Valenzuela VV, Frank RT, Barish ME, Brown CE, Kim SU, Badie B, Portnow J (2013) Neural stem cell-mediated enzyme/prodrug therapy for glioma: preclinical studies. Sci Transl Med 5(184): 184ra59. https://doi.org/10.1126/scitranslmed.3005365

Acosta SA, Tajiri N, Hoover J, Kaneko Y (2015) Intravenous bone marrow stem cell grafts preferentially migrate to spleen and abrogate chronic inflammation in stroke. Stroke 46(9): 2616−2627

Ahmed AS, Sheng MH, Wasnik S, Baylink DJ, Lau KW (2017) Effect of aging on stem cells. World J Exp Med 7(1): 1−10

Bang OY (2016) Clinical trials of adult stem cell therapy in patients with ischemic stroke. J Clin Neurol 12(1): 14−20

Boehme A, Esenwa C, Elkind M (2017) Stroke risk factors, genetics, and prevention. Circ Res 120(3): 472−495

Cho S-W, Kim S-S, Won Rhie J, Mi Cho H, Yong Choi C, Kim B-S (2005) Engineering of volume-stable adipose tissues. Biomaterials 26(17): 3577−3585

Christiaens V, Lijnen HR (2010) Angiogenesis and development of adipose tissue. Mol Cell Endocrinol 318(1): 2−9

Coccè V, Farronato D, Brini A, Masia C, Giannì A, Piovani G, Sisto F, Alessandri G, Angiero F, Pessina A (2017) Drug loaded gingival mesenchymal stromal cells (GinPa-MSCs) inhibit in vitro proliferation of oral squamous cell carcinoma. Sci Rep 7(1): 9376. https://doi.org/10.1038/s41598-017-09175-4

Coccè V, Franzè S, Brini AT, Giannì AB, Pascucci L, Ciusani E, Alessandri G, Farronato G, Cavicchini L, Sordi V, Paroni R, Cas MD, Cilurzo F, Pessina A (2019) In vitro anticancer activity of extracellular vesicles (EVs) secreted by gingival mesenchymal stromal cells primed with paclitaxel. Pharmaceutics 11(2): 61. https://doi.org/10.3390/pharmaceutics11020061

Eyrich D, Göpferich A, Blunk T (2006) Fibrin in tissue engineering. Adv Exp Med Biol 585: 379−392

Fitzsimmons REB, Mazurek MS, Soos A, Simmons CA (2018) Mesenchymal stromal/stem cells in regenerative medicine and tissue engineering. Stem Cell Int 2018: 8031718. https://doi.org/10.1155/2018/8031718

Gesta S, Tseng Y-H, Kahn CR (2008) Developmental origin of fat: tracking obesity to its source. Cell 135(2): 366−366

Gomillion CT, Burg KJL (2006) Stem cells and adipose tissue engineering. Biomaterials 27(36): 6052−6063

Göpferich A (1996) Mechanisms of polymer degradation and erosion. Biomaterials 17(2): 103−114

Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J (2019) Mesenchymal stem cells for regenerative medicine. Cells 8(8): 886. https://doi.org/10.3390/cells8080886

Hossain J, Latif MA, Ystaas LAR, Ninzima S, Riecken K, Muller A, Azuaje F, Vareecal Joseph J, Talasila KM, Ghimire J, Fehse B, Bjerkvig R, Miletic H (2019) Long-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastoma. Neuro Oncol 21(7): 890−900

Hsuan YCY, Lin CH, Chang CP, Lin MT (2016) Mesenchymal stem cell-based treatments for stroke, neural trauma, and heat stroke. Brain Behav 6(10): 1−11

Kawaguchi N, Toriyama K, Nicodemou-Lena E, Inou K, Torii S, Kitagawa Y (1998) De novo adipogenesis in mice at the site of injection of basement membrane and basic fibroblast growth factor. Proc Natl Acad Sci USA 95(3): 1062−1066

Kimura Y, Ozeki M, Inamoto T, Tabata Y (2002) Time course of de novo adipogenesis in matrigel by gelatin microspheres incorporating basic fibroblast growth factor. Tissue Eng 8(4): 603−613

Kievit E, Bershad E, Ng E, Sethna P, Dev I, Lawrence TS, Rehemtulla A (1999) Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts. Cancer Res 59(7): 1417−1421

Korkegian A, Black ME, Baker D, Stoddard BL (2005) Computational thermostabilization of an enzyme. Science 308(5723): 857−860

Koton S, Telman G, Kimiagar I, Tanne D (2013) Gender differences in characteristics, management and outcome at discharge and three months after stroke in a national acute stroke registry. Int J Cardiol 168(4): 4081−4084

Koyuncu S, Irmak D, Saez I, Vilchez D (2015) Defining the general principles of stem cell aging: lessons from organismal models. Curr Stem Cell Rep 1: 162−169

Kurtzberg J, Prasad V, Grimley M, Horn B, Carpenter P, Jacobsohn D, Prockop S (2010) Allogeneic human mesenchymal stem cell therapy (Prochymal®) as a rescue agent for severe treatment resistant GVHD in pediatric patients. Biol Blood Marrow Transplant 16: S169. https://doi.org/10.1016/j.bbmt.2009.12.056

Li S, Tokuyama T, Yamamoto J, Koide M, Yokota N, Namba H (2005) Bystander effect-mediated gene therapy of gliomas using genetically engineered neural stem cells. Cancer Gene Ther 12(7): 600−607

Li J, Mooney D (2016) Designing hydrogels for controlled drug delivery. Nat Rev Mater 1(12): 16071. https://doi.org/10.1038/natrevmats.2016.71

Miana VV, Prieto González EA (2018) Adipose tissue stem cells in regenerative medicine. Ecancer 12: 822. https://doi.org/10.3332/ecancer.2018.822

Nava S, Sordi V, Pascucci L, Tremolada C, Ciusani E, Zeira O, Cadei M, Soldati G, Pessina A, Parati E, Slevin M, Alessandri G (2019) Long-lasting anti-inflammatory activity of human microfragmented adipose tissue. Stem Cell Int 2019: 5901479. https://doi.org/10.1155/2019/5901479

Momin EN, Mohyeldin A, Zaidi HA, Vela G, Quinones-Hinojosa A (2010) Mesenchymal stem cells: new approaches for the treatment of neurological diseases. Curr Stem Cell Res Ther 5(4): 326−344

Oberbauer E, Steffenhagen C, Wurzer C, Gabriel C, Redl H, Wolbank S (2015) Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells: current state of the art. Cell Regen 4: 7. https://doi.org/10.1186/s13619-015-0020-0

Panchal J, Malanga G, Sheinkop M (2018) Safety and efficacy of percutaneous injection of lipogems micro-fractured adipose tissue for osteoarthritic knees. Am J Orthop (Belle Mead NJ) 47(11). https://doi.org/10.12788/ajo.2018.0098

Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Diez MC, Tagarro I, Leselbaum A, Danese S, ADMIRE CD Study Group Collaborators (2018) Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn's disease. Gastroenterology 154(5): 1334−1342

Patrick JCW, Chauvin PB, Hobley J, Reece GP (1999) Preadipocyte seeded PLGA scaffolds for adipose tissue engineering. Tissue Eng 5(2): 139−151

Popa-Wagner A, Buga A, Doeppner T, Hermann D (2014) Stem cell therapies in preclinical models of stroke associated with aging. Front Cell Neurosci 8: 347. https://doi.org/10.3389/fncel.2014.00347

Popa-Wagner A, Petcu E, Capitanescu B, Hermann D, Radu E, Gresita A (2020) Ageing as a risk factor for cerebral ischemia: underlying mechanisms and therapy in animal models and in the clinic. Mech Ageing Dev 190: 111312. https://doi.org/10.1016/j.mad.2020.111312

Randelli P, Menon A, Ragone V, Creo P, Bergante S, Randelli F, De Girolamo L, Alfieri Montrasio U, Banfi G, Cabitza P, Tettamanti G, Anastasia L (2016) Lipogems product treatment increases the proliferation rate of human tendon stem cells without affecting their stemness and differentiation capability. Stem Cells Int 2016: 4373410. https://doi.org/10.1155/2016/4373410

Roato I, Mussano F, Reano S, Boriani F, Margara A, Ferracini R, Adriani E, SabryO, Fiorini M, Fattori P (2020) A novel method to optimize autologous adipose tissue recovery with extracellular matrix preservation. Processes 8(1): 88. https://doi.org/10.3390/pr8010088

Srijaya T C, Ramasamy TS, Kasim NHA (2014) Advancing stem cell therapy from bench to bedside: lessons from drug therapies. J Transl Med 12: 243. https://doi.org/10.1186/s12967-014-0243-9

Tatarishvili J, Okia K, Monnia E, Kochb P, Memanishvilia T, Bugad AM, Vermaa V, Popa-Wagnerd A, Brustleb O, Lindvallaand O, Kokaiaa Z (2014) Human induced pluripotent stem cellsimprove recovery in stroke-injured aged rats. Restor Neurol Neurosci 32(4): 547−558

Tremolada C, Colombo V, Ventura C (2016) Adipose tissue and mesenchymal stem cells: state of the art and Lipogems® technology development. Curr Stem Cell Rep 2(3): 304−312

Trivisonno A, Alexander RW, Baldari S, Cohen SR, Di Rocco G, Gentile P, Magalon G, Magalon J, Miller RB, Womack H, Toietta G (2019) Intraoperative strategies for minimal manipulation of autologous adipose tissue for cell- and tissue-based therapies: concise review. Stem Cells Transl Med 8(12): 1265−1271

Tsuji W, Inamoto T, Yamashiro H, Ueno T, Kato H, Kimura Y, Tabata Y, Toi M (2009) Adipogenesis induced by human adipose tissue-derived stem cells. Tissue Eng 15(1): 83−93

von Heimburg D, Zachariah S, Kühling H, Heschel I, Schoof H, Hafemann B, Pallua N (2001) Human preadipocytes seeded on freeze-dried collagen scaffolds investigated in vitro and in vivo. Biomaterials 22(5): 429−438

Walton RL, Beahm K, Wu L (2004) De novo adipose formation in a vascularized engineered construct. Microsurgery 24(5): 378−384

Zeira O, Scaccia S, Pettinari L, Ghezzi E, Asiag N, Martinelli L, Zahirpour D, Dumas M, Konar M, Lupi D, Fiette L, Pascucci L, Leonardi L, Cliff A, Alessandri G, Pessina A, Spaziante D, Aralla M (2018) Intra-Articular administration of autologous micro-fragmented adipose tissue in dogs with spontaneous osteoarthritis: safety, feasibility, and clinical outcomes. Stem Cells Transl Med 7(11): 819−828

Publication history
Copyright
Rights and permissions

Publication history

Received: 09 July 2020
Accepted: 06 February 2021
Published: 17 May 2021
Issue date: April 2021

Copyright

© The Author(s) 2021

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Return