Human Adipose-Derived Stem Cells with Great Therapeutic Potential

Author(s): Mohsen Sheykhhasan, Joanna K.L. Wong, Alexander M. Seifalian*

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 7 , 2019

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The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in regenerative medicine. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. While clinically, adipose-derived stem cells (ADSCs) are one of the most widely used types of stem cells used more than five years in clinically setting. It has many advantages including; yields a high number of ADSCs per volume of tissue, high rate of proliferation, anti-fibrotic, anti-apoptotic, anti-inflammation, immunomodulation, and paracrine mechanisms have been demonstrated in various preclinical studies. It is much easier to harvest compared with bone marrow stem cells. Results of clinical studies have demonstrated the potentials of ADSCs for stem cells therapy for a number of clinical disorders. The aim of this paper was to provide an update on the most recent developments of ADSCs, by highlighting the properties and features of ADSCs, critically discussing its clinical benefit and its clinical trials in treatment and regeneration. This is a multi-billion dollars industry with huge interest to clinician, academia and industries.

Keywords: Adipose-derived stem cells, therapeutic medicine, wound lesions, respiratory disease, bone and cartilage diseases, crohn’s disease, neurological disease, kidney disease, heart diseases, urological dysfunctions, cosmetic and plastic surgery.

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.
Lendeckel S, Jödicke A, Christophis P, et al. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. J Craniomaxillofac Surg 2004; 32(6): 370-3.
Thesleff T, Lehtimäki K, Niskakangas T, et al. Cranioplasty with adipose-derived stem cells, beta-tricalcium phosphate granules and supporting mesh: Six-year clinical follow-up results. Stem Cells Transl Med 2017; 6(7): 1576-82.
Johal KS, Lees VC, Reid AJ. Adipose-derived stem cells: Selecting for translational success. Regen Med 2015; 10(1): 79-96.
Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived stem cells in regenerative medicine. Transfus Med Hemother 2016; 43(4): 268-74.
Tsuji W, Rubin JP, Marra KG. Adipose-derived stem cells: Implications in tissue regeneration. World J Stem Cells 2014; 6(3): 312-21.
Tabatabaei Qomi R, Sheykhhasan M. Adipose-derived stromal cell in regenerative medicine: A review. World J Stem Cells 2017; 9(8): 107-17.
Zhao L, Johnson T, Liu D. Therapeutic angiogenesis of adipose-derived stem cells for ischemic diseases. Stem Cell Res Ther 2017; 8(1): 125.
Wankhade UD, Shen M, Kolhe R, Fulzele S. Advances in adipose-derived stem cells isolation, characterization, and application in regenerative tissue engineering. Stem Cells Int 2016; 20163206807
Ghiasi M, Kalhor N, Tabatabaei Qomi R, Sheykhhasan M. The effects of synthetic and natural scaffolds on viability and proliferation of adipose-derived stem cells. Front Life Sci 2016; 9(1): 32-43.
Valencia J, Blanco B, Yáñez R, et al. Comparative analysis of the immunomodulatory capacities of human bone marrow-and adipose tissue-derived mesenchymal stromal cells from the same donor. Cytotherapy 2016; 18(10): 1297-311.
Oberbauer E, Steffenhagen C, Wurzer C, Gabriel C, Redl H, Wolbank S. Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells: Current state of the art. Cell Regen (Lond) 2015; 4: 7.
Roemeling-van Rhijn M, Khairoun M, Korevaar SS, et al. Human bone marrow-and adipose tissue-derived mesenchymal stromal cells are immunosuppressive in vitro and in a humanized allograft rejection model. J Stem Cell Res Ther 2013; Suppl 6(1): 20780.
Hao T, Chen J, Zhi S, Zhang Q, Chen G, Yu F. Comparison of bone marrow-vs. adipose tissue-derived mesenchymal stem cells for attenuating liver fibrosis. Exp Ther Med 2017; 14(6): 5956-64.
Griffin M, Kalaskar DM, Butler PE, Seifalian AM. The use of adipose stem cells in cranial facial surgery. Stem Cell Rev 2014; 10(5): 671-85.
Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res 2007; 100(9): 1249-60.
Casadei A, Epis R, Ferroni L, et al. Adipose tissue regeneration: A state of the art. J Biomed Biotechnol 2012; 2012462543
Sheykhhasan M, Qomi RT, Ghiasi M. Fibrin scaffolds designing in order to human adipose-derived mesenchymal stem cells differentiation to chondrocytes in the presence of TGF-β3. Int J Stem Cells 2015; 8(2): 219-27.
Sheykhhasan M, Qomi RT, Kalhor N, Mehdizadeh M, Ghiasi M. Evaluation of the ability of natural and synthetic scaffolds in providing an appropriate environment for growth and chondrogenic differentiation of adipose-derived mesenchymal stem cells. Indian J Orthop 2015; 49(5): 561-8.
Gnecchi M, Danieli P, Malpasso G, Ciuffreda MC. Paracrine mechanisms of mesenchymal stem cells in tissue repair. Methods Mol Biol 2016; 1416: 123-46.
Yao Y, Zheng Z, Song Q. Mesenchymal stem cells: A double-edged sword in radiation-induced lung injury. Thorac Cancer 2018; 9(2): 208-17.
Kocan B, Maziarz A, Tabarkiewicz J, Ochiya T, Banaś-Ząbczyk A. trophic activity and phenotype of adipose tissue-derived mesenchymal stem cells as a background of their regenerative potential. Stem Cells Int 2017; 20171653254
Meng F, Zhou D, Li W. Adipose-derived stem cells as a potential weapon for diabetic foot ulcers. Int J Clin Exp Med 2017; 10(12): 15967-73.
Almubarak S, Nethercott H, Freeberg M, et al. Tissue engineering strategies for promoting vascularized bone regeneration. Bone 2016; 83: 197-209.
Zhang H, Ning H, Banie L, et al. Adipose tissue-derived stem cells secrete CXCL5 cytokine with chemoattractant and angiogenic properties. Biochem Biophys Res Commun 2010; 402(3): 560-4.
Park B-S, Kim W-S. Adipose-Derived Stem Cells and Their Secretory Factors for Skin Aging and Hair Loss. In: Miranda A. Farage, Kenneth W. Miller, Howard I. Maibach, Eds. Textbook of Aging Skin. Springer-Verlag Berlin Heidelberg 2017; pp. 205-24.
Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, LeRoux MA. Concise review: Role of mesenchymal stem cells in wound repair. Stem Cells Transl Med 2012; 1(2): 142-9.
Tran C, Damaser MS. Stem cells as drug delivery methods: Application of stem cell secretome for regeneration. Adv Drug Deliv Rev 2015; 82-83: 1-11.
Sun Z, Nair LS, Laurencin CT. The paracrine effect of adipose-derived stem cells inhibits IL-1β-induced inflammation in chondrogenic cells through the Wnt/β-catenin signaling pathway. Regen Eng Transl Med 2018; 4(1): 35-41.
Xue C, Shen Y, Li X, et al. Exosomes derived from hypoxia-treated human adipose mesenchymal stem cells enhance angiogenesis through the PKA signaling pathway. Stem Cells Dev 2018; 27(7): 456-65.
Dai M, Zhang Y, Yu M, Tian W. Therapeutic applications of conditioned medium from adipose tissue. Cell Prolif 2016; 49(5): 561-7.
Gaur M, Dobke M, Lunyak VV. Mesenchymal stem cells from adipose tissue in clinical applications for dermatological indications and skin aging. Int J Mol Sci 2017; 18(1)E208
Spiekman M, Dongen JA, Willemsen JC, Hoppe DL, Lei B, Harmsen MC. The power of fat and its adipose-derived stromal cells: Emerging concepts for fibrotic scar treatment. J Tissue Eng Regen Med 2017; 11(11): 3220-35.
Granel B, Daumas A, Jouve E, et al. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: An open-label phase I trial. Ann Rheum Dis 2015; 74(12): 2175-82.
Dittmer J, Leyh B. Paracrine effects of stem cells in wound healing and cancer progression. Int J Oncol 2014; 44(6): 1789-98.
Linero I, Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One 2014; 9(9)e107001
Mitchell JB, McIntosh K, Zvonic S, et al. Immunophenotype of human adipose‐derived cells: Temporal changes in stromal‐associated and stem cell-associated markers. Stem Cells 2006; 24(2): 376-85.
Yoshimura K, Shigeura T, Matsumoto D, et al. Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates. J Cell Physiol 2006; 208(1): 64-76.
Jacobs SA, Roobrouck VD, Verfaillie CM, Van Gool SW. Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells. Immunol Cell Biol 2013; 91(1): 32-9.
Kim I, Bang SI, Lee SK, Park SY, Kim M, Ha H. Clinical Implication of Allogenic Implantation of Adipogenic Differentiated Adipose‐Derived Stem Cells. Stem Cells Transl Med 2014; 3(11): 1312-21.
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.
Griffin M, Ibrahim A, Seifalian A, Butler P, Kalaskar D, Ferretti P. Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages. Acta Biomater 2017; 50: 450-61.
New SE, Ibrahim A, Guasti L, et al. Towards reconstruction of epithelialized cartilages from autologous adipose tissue‐derived stem cells. J Tissue Eng Regen Med 2017; 11(11): 3078-89.
Liu Y, Zhang Z, Qin Y, et al. A new method for Schwann-like cell differentiation of adipose derived stem cells. Neurosci Lett 2013; 551: 79-83.
Naderi N, Karponis D, Mosahebi A, Seifalian AM. Nanoparticles in wound healing; from hope to promise, from promise to routine. Front Biosci(Landmark Ed) 2018; 23: 1038-59.
Owczarczyk-Saczonek A, Wociór A, Placek W, Maksymowicz W, Wojtkiewicz J. The use of adipose-derived stem cells in selected skin diseases (Vitiligo, Alopecia, and Nonhealing Wounds). Stem Cells Int 2017; 20174740709
Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med 2014. 3; 6(265): 265sr6.
Raposio E, Bertozzi N, Grignaffini E, Simonacci F, Grieco MP. Adipose-derived stem cells for treatment of chronic cutaneous ulcers in patients with critical limb ischemia: A pilot study. Eur J Plast Surg 2017; 1-6.
Kuo Y-R, Wang C-T, Cheng J-T, Kao G-S, Chiang Y-C, Wang C-J. Adipose-derived stem cells accelerate diabetic wound healing through the induction of autocrine and paracrine effects. Cell Transplant 2016; 25(1): 71-81.
Ma N, Qiao C, Zhang W, et al. Adipose-derived stem cells from younger donors, but not aging donors, inspire the host self-healing capability through its secreta. Exp Biol Med (Maywood) 2017; 242(1): 68-79.
Gholipourmalekabadi M, Sameni M, Radenkovic D, Mozafari M, Mossahebi‐Mohammadi M, Seifalian A. Decellularized human amniotic membrane: how viable is it as a delivery system for human adipose tissue derived stromal cells? Cell Prolif 2016; 49(1): 115-21.
Bertozzi N, Simonacci F, Grieco MP, Grignaffini E, Raposio E. The biological and clinical basis for the use of adipose-derived stem cells in the field of wound healing. Ann Med Surg (Lond) 2017; 20: 41-8.
Naderi N, Combellack EJ, Griffin M, et al. The regenerative role of adipose‐derived stem cells (ADSC) in plastic and reconstructive surgery. Int Wound J 2017; 14(1): 112-24.
Chavez-Munoz C, Nguyen KT, Xu W, Hong S-J, Mustoe TA, Galiano RD. Transdifferentiation of adipose-derived stem cells into keratinocyte-like cells: Engineering a stratified epidermis. PLoS One 2013; 8(12)e80587
Hu L, Wang J, Zhou X, et al. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Sci Rep 2016; 6: 32993.
Lee SM, Lee SC, Kim S-J. Contribution of human adipose tissue-derived stem cells and the secretome to the skin allograft survival in mice. J Surg Res 2014; 188(1): 280-9.
Zhou B-R, Xu Y, Guo S-L, et al. The effect of conditioned media of adipose-derived stem cells on wound healing after ablative fractional carbon dioxide laser resurfacing. BioMed Res Int 2013; 2013519126
Reckhenrich AK, Kirsch BM, Wahl EA, et al. Surgical sutures filled with adipose-derived stem cells promote wound healing. PLoS One 2014; 9(3)e91169
Loder S, Peterson JR, Agarwal S, et al. Wound healing after thermal injury is improved by fat and adipose-derived stem cell isografts. J Burn Care Res 2015; 36(1): 70-6.
Bliley JM, Argenta A, Satish L, et al. Administration of adipose-derived stem cells enhances vascularity, induces collagen deposition, and dermal adipogenesis in burn wounds. Burns 2016; 42(6): 1212-22.
Klar AS, Zimoch J, Biedermann T. Skin tissue engineering: Application of adipose-derived stem cells. BioMed Res Int 2017; 20179747010
Arshad Z, Karmen L, Choudhary R, et al. Cell assisted lipotransfer in breast augmentation and reconstruction: A systematic review of safety, efficacy, use of patient reported outcomes and study quality. JPRAS Open 2016; 10: 5-20.
Liu X, Han J. Research progress on the safety of cell-assisted lipotransfer in breast repairs after breast conserving therapy. Adv Mod Oncol Res 2016; 2(2): 70-3.
Banyard DA, Salibian AA, Widgerow AD, Evans GR. Implications for human adipose‐derived stem cells in plastic surgery. J Cell Mol Med 2015; 19(1): 21-30.
Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: Supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg 2008; 32(1): 48-55. discussion 56-7.
Clauser L, Lucchi A, Tocco-Tussardi I, Gardin C, Zavan B. Autologous fat transfer for facial augmentation and regeneration: Role of mesenchymal stem cells. Atlas Oral Maxillofac Surg Clin North Am 2018; 26(1): 25-32.
Berman M, Lander E. A prospective safety study of autologous adipose-derived stromal vascular fraction using a specialized surgical processing system. Am J Cosmet Surg 2017; 34(3): 129-42.
Toyserkani NM, Jørgensen MG, Tabatabaeifar S, Jensen CH, Sheikh SP, Sørensen JA. Concise review: A safety assessment of adipose‐derived cell therapy in clinical Trials: A systematic review of reported adverse events. Stem Cells Transl Med 2017; 6(9): 1786-94.
Arshad Z, Halioua-Haubold C-L, Roberts M, et al. Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape. Aesthet Surg J 2018; 38(2): 199-210.
Naderi N, Wilde C, Haque T, et al. Adipogenic differentiation of adipose-derived stem cells in 3-dimensional spheroid cultures (microtissue): implications for the reconstructive surgeon. J Plast Reconstr Aesthet Surg 2014; 67(12): 1726-34.
Luan A, Duscher D, Whittam AJ, et al. Cell‐assisted lipotransfer improves volume retention in irradiated recipient sites and rescues radiation‐induced skin changes. Stem Cells 2016; 34(3): 668-73.
Chen Y-S, Hsueh Y-S, Chen Y-Y, Lo C-Y, Tai H-C, Lin F-H. Evaluation of a laminin-alginate biomaterial, adipocytes, and adipocyte-derived stem cells interaction in animal autologous fat grafting model using 7-Tesla magnetic resonance imaging. J Mater Sci Mater Med 2017; 28(1): 18.
Jiang T, Xie Y, Zhu M, et al. The second fat graft has significantly better outcome than the first fat graft for Romberg syndrome: A study of three-dimensional volumetric analysis. J Plast Reconstr Aesthet Surg 2016; 69(12): 1621-6.
Reddy M, Fonseca L, Gowda S, Chougule B, Hari A, Totey S. Human adipose-derived mesenchymal stem cells attenuate early stage of bleomycin induced pulmonary fibrosis: Comparison with pirfenidone. Int J Stem Cells 2016; 9(2): 192-206.
Totey S. Idiopathic Pulmonary Fibrosis: Stem Cell-Mediated Therapeutic Approach Regenerative Medicine: Laboratory to Clinic. Springer 2017; pp. 511-29.
Cervellione KL, Raynor J, Desai P, Thurm CA. Acute respiratory failure in a patient with idiopathic pulmonary fibrosis following nebulized and intravenous stem cell therapy. J Med Cases 2017; 8(10): 301-14.
Llontop P, Lopez-Fernandez D, Clavo B, et al. Airway transplantation of adipose stem cells protects against bleomycin-induced pulmonary fibrosis. J Investig Med 2018; 66(4): 739-46.
Ntolios P, Manoloudi E, Tzouvelekis A, et al. Longitudinal outcomes of patients enrolled in a Phase Ib clinical trial of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis. Clin Respir J 2018; 12(6): 2084-9.
Antunes MA, Silva JRL, Rocco PR. Mesenchymal stromal cell therapy in COPD: From bench to bedside. Int J Chron Obstruct Pulmon Dis 2017; 12: 3017-27.
Sun Z, Li F, Zhou X, Chung KF, Wang W, Wang J. Stem cell therapies for chronic obstructive pulmonary disease: Current status of pre-clinical studies and clinical trials. J Thorac Dis 2018; 10(2): 1084-98.
Silva LH, Antunes MA, Dos Santos CC, Weiss DJ, Cruz FF, Rocco PR. Strategies to improve the therapeutic effects of mesenchymal stromal cells in respiratory diseases. Stem Cell Res Ther 2018; 9(1): 45.
Qian J, Hu Y, Zhao L, et al. Protective role of adipose‐derived stem cells in Staphylococcus aureus‐induced lung injury is mediated by RegIIIγ secretion. Stem Cells 2016; 34(7): 1947-56.
Goldberg G, Stockhausen S. Atlas of Anatomy, General Anatomy and Musculoskeletal System. LWW 2015.
Loeser RF. Age-related changes in the musculoskeletal system and the development of osteoarthritis. Clin Geriatr Med 2010; 26(3): 371-86.
Freitag J, Shah K, Wickham J, Boyd R, Tenen A. The effect of autologous adipose derived mesenchymal stem cell therapy in the treatment of a large osteochondral defect of the knee following unsuccessful surgical intervention of osteochondritis dissecans-a case study. BMC Musculoskelet Disord 2017; 18(1): 298.
Gobbi A, de Girolamo L, Whyte GP, Sciarretta FV. Clinical applications of adipose tissue-derived stem cells Bio-orthopaedics. Springer 2017; pp. 553-9.
Sun Q, Zhang L, Xu T, et al. Combined use of adipose derived stem cells and TGF-β3 microspheres promotes articular cartilage regeneration in vivo. Biotech Histochem 2018; 93(3): 168-76.
Perdisa F, Gostyńska N, Roffi A, Filardo G, Marcacci M, Kon E. Adipose-derived mesenchymal stem cells for the treatment of articular cartilage: A systematic review on preclinical and clinical evidence. Stem Cells Int 2015; 2015597652
Zhong J, Guo B, Xie J, et al. Crosstalk between adipose-derived stem cells and chondrocytes: When growth factors matter. Bone Res 2016; 4: 15036.
Simonacci F, Bertozzi N, Raposio E. Off-label use of adipose-derived stem cells. Ann Med Surg (Lond) 2017; 24: 44-51.
nc MO, Santidrian A, Minev I, Toth R, Draganov D, Nguyen D, Lander E, Berman M, Minev B, Szalay AA. The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy. Clin Transl Med 2018; 7(1): 5.
Pers Y-M, Rackwitz L, Ferreira R, et al. Adipose mesenchymal stromal cell‐based therapy for severe osteoarthritis of the knee: A phase I dose‐escalation trial. Stem Cells Transl Med 2016; 5(7): 847-56.
Tantuway V, Bhambani P, Nagla A, et al. Autologous grafting of non manupulated freshly isolated-adipose tissue derived stromal vascular fraction in single surgical sitting for treatment of knee osteoarthritis. Int J Res Orthop 2016; 3(1): 107-15.
Nguyen PD, Tran TDX, Nguyen HTN, et al. Comparative clinical observation of arthroscopic microfracture in the presence and absence of a stromal vascular fraction injection for osteoarthritis. Stem Cells Transl Med 2017; 6(1): 187-95.
Pak J, Lee JH, Park KS, Jeong BC, Lee SH. Regeneration of cartilage in human knee osteoarthritis with autologous adipose tissue-derived stem cells and autologous extracellular matrix. Biores Open Access 2016; 5(1): 192-200.
Barba M, Di Taranto G, Lattanzi W. Adipose-derived stem cell therapies for bone regeneration. Expert Opin Biol Ther 2017; 17(6): 677-89.
Mizuno H, Tobita M, Ogawa R, et al. Adipose-Derived Stem Cells in Regenerative Medicine Principles of Gender-Specific Medicine. (Third Edition):. Elsevier 2017; pp. 459-79.
Alabdulkarim Y, Ghalimah B, Al-Otaibi M, et al. Recent advances in bone regeneration: The role of adipose tissue-derived stromal vascular fraction and mesenchymal stem cells. J Limb Lengthening Reconstr 2017; 3(1): 4-18.
Fishero BA, Kohli N, Das A, Christophel JJ, Cui Q. Current concepts of bone tissue engineering for craniofacial bone defect repair. Craniomaxillofac Trauma Reconstr 2015; 8(1): 23-30.
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; 11(3): 140-50.
Paduano F, Marrelli M, Amantea M, et al. Adipose tissue as a strategic source of mesenchymal stem cells in bone regeneration: A topical review on the most promising craniomaxillofacial applications. Int J Mol Sci 2017; 18(10)E2140
Toratani T, Nakase J, Numata H, et al. Scaffold-free tissue-engineered allogenic adipose-derived stem cells promote meniscus healing. Arthroscopy 2017; 33(2): 346-54.
Korpershoek JV, de Windt TS, Hagmeijer MH, Vonk LA, Saris DB. Cell-based meniscus repair and regeneration: At the brink of clinical translation? a systematic review of preclinical studies. Orthop J Sports Med 2017; 5(2)2325967117690131
Richardson SM, Kalamegam G, Pushparaj PN, et al. Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods 2016; 99: 69-80.
Zeckser J, Wolff M, Tucker J, Goodwin J. Multipotent mesenchymal stem cell treatment for discogenic low back pain and disc degeneration. Stem Cells Int 2016; 20163908389
Jeong JH, Lee JH, Jin ES, Min JK, Jeon SR, Choi KH. Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissue-derived stromal cells. Acta Neurochir (Wien) 2010; 152(10): 1771-7.
Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2015; 23(5): 1308-16.
Koh YG, Choi YJ, Kwon OR, Kim YS. Second-look arthroscopic evaluation of cartilage lesions after mesenchymal stem cell implantation in osteoarthritic knees. Am J Sports Med 2014; 42(7): 1628-37.
Geltzeiler CB, Wieghard N, Tsikitis VL. Recent developments in the surgical management of perianal fistula for Crohn’s disease. Ann Gastroenterol 2014; 27(4): 320.
De Francesco F, Romano M, Zarantonello L, et al. The role of adipose stem cells in inflammatory bowel disease: From biology to novel therapeutic strategies. Cancer Biol Ther 2016; 17(9): 889-98.
Choi S, Ryoo S-B, Park K, et al. Autologous adipose tissue-derived stem cells for the treatment of complex perianal fistulas not associated with Crohn’s disease: A phase II clinical trial for safety and efficacy. Tech Coloproctol 2017; 21(5): 345-53.
García-Olmo D, García-Arranz M, García LG, et al. Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn’s disease: a new cell-based therapy. Int J Colorectal Dis 2003; 18(5): 451-4.
García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 2005; 48(7): 1416-23.
Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: A phase II clinical trial. Dis Colon Rectum 2009; 52(1): 79-86.
Garcia-Olmo D, Garcia-Arranz M, Herreros D. Expanded adipose-derived stem cells for the treatment of complex perianal fistula including Crohn’s disease. Expert Opin Biol Ther 2008; 8(9): 1417-23.
García-Arranz M, Herreros MD, González-Gómez C, et al. Treatment of Crohn’s‐Related rectovaginal fistula with allogeneic expanded‐adipose derived stem cells: A Phase I-IIa Clinical Trial. Stem Cells Transl Med 2016; 5(11): 1441-6.
Guadalajara H, Herreros D, De-La-Quintana P, Trebol J, Garcia-Arranz M, Garcia-Olmo D. Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas. Int J Colorectal Dis 2012; 27(5): 595-600.
De la Portilla F, Alba F, Garcia-Olmo D, Herrerías J, González F, Galindo A. Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn’s disease: Results from a multicenter phase I/IIa clinical trial. Int J Colorectal Dis 2013; 28(3): 313-23.
Lee WY, Park KJ, Cho YB, et al. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn’s fistula. Stem Cells 2013; 31(11): 2575-81.
Lombardo E, van der Poll T, DelaRosa O, Dalemans W. Mesenchymal stem cells as a therapeutic tool to treat sepsis. World J Stem Cells 2015; 7(2): 368.
Park K, Ryoo SB, Kim J, et al. Allogeneic adipose‐derived stem cells for the treatment of perianal fistula in Crohn’s disease: A pilot clinical trial. Colorectal Dis 2016; 18(5): 468-76.
Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: A phase 3 randomised, double-blind controlled trial. The Lancet 2016; 388(10051): 1281-90.
Cho YB, Park KJ, Yoon SN, et al. Long-term results of adipose-derived stem cell therapy for the treatment of Crohn’s fistula. Stem Cells Transl Med 2015; 4(5): 532-7.
Erba P, Terenghi GJ, Kingham P. Neural differentiation and therapeutic potential of adipose tissue derived stem cells. Curr Stem Cell Res Ther 2010; 5(2): 153-60.
Tomita K, Madura T, Mantovani C, Terenghi G. Differentiated adipose-derived stem cells promote myelination and enhance functional recovery in a rat model of chronic denervation. J Neurosci Res 2012; 90(7): 1392-402.
Jang S, Cho HH, Cho YB, Park JS, Jeong HS. Functional neural differentiation of human adipose tissue-derived stem cells using bFGF and forskolin. BMC Cell Biol 2010; 11(1): 25.
Liao D, Gong P, Li X, Tan Z, Yuan Q. Co-culture with Schwann cells is an effective way for adipose-derived stem cells neural transdifferentiation. Arch Med Sci 2010; 6(2): 145.
Xu Y, Zhang Z, Chen X, Li R, Li D, Feng S. A silk fibroin/collagen nerve scaffold seeded with a co-culture of schwann cells and adipose-derived stem cells for sciatic nerve regeneration. PLoS One 2016; 11(1)e0147184
Ha S, Park H, Mahmood U, Ra JC, Suh Y-H, Chang K-A. Human adipose-derived stem cells ameliorate repetitive behavior, social deficit and anxiety in a VPA-induced autism mouse model. Behav Brain Res 2017; 317: 479-84.
Hur JW, Cho T-H, Park D-H, Lee J-B, Park J-Y, Chung Y-G. Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial. J Spinal Cord Med 2016; 39(6): 655-64.
Chung HC, Ko IK, Atala A, Yoo JJ. Cell-based therapy for kidney disease. Korean J Urol 2015; 56(6): 412-21.
Lin K-C, Yip H-K, Shao P-L, et al. Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury. Int J Cardiol 2016; 216: 173-85.
Chen HH, Lin KC, Wallace CG, et al. Additional benefit of combined therapy with melatonin and apoptotic adipose‐derived mesenchymal stem cell against sepsis‐induced kidney injury. J Pineal Res 2014; 57(1): 16-32.
Yip HK, Chang YC, Wallace CG, et al. Melatonin treatment improves adipose‐derived mesenchymal stem cell therapy for acute lung ischemia-reperfusion injury. J Pineal Res 2013; 54(2): 207-21.
Tran C, Damaser MS. The potential role of stem cells in the treatment of urinary incontinence. Ther Adv Urol 2015; 7(1): 22-40.
Sheashaa H, Lotfy A, Elhusseini F, et al. Protective effect of adipose-derived mesenchymal stem cells against acute kidney injury induced by ischemia-reperfusion in Sprague-Dawley rats. Exp Ther Med 2016; 11(5): 1573-80.
Chen Y-T, Yang C-C, Zhen Y-Y, et al. Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury. Stem Cell Res Ther 2013; 4(3): 62.
Chen Y-T, Sun C-K, Lin Y-C, et al. Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction. J Transl Med 2011; 9(1): 51.
Furuichi K, Shintani H, Sakai Y, Ochiya T, Matsushima K, Kaneko S, et al. Effects of adipose-derived mesenchymal cells on ischemia-reperfusion injury in kidney. J Clin Exp Nephrol 2012; 16(5): 679-89.
Chang CL, Sung PH, Sun CK, et al. Protective effect of melatonin‐supported adipose‐derived mesenchymal stem cells against small bowel ischemia‐reperfusion injury in rat. J Pineal Res 2015; 59(2): 206-20.
Burgos-Silva M, Semedo-Kuriki P, Donizetti-Oliveira C, et al. Adipose tissue-derived stem cells reduce acute and chronic kidney damage in mice. PLoS One 2015; 10(11)e0142183
He X, Zhang Y, Zhu A, et al. Suppression of interleukin 17 contributes to the immunomodulatory effects of adipose-derived stem cells in a murine model of systemic lupus erythematosus. Immunol Res 2016; 64(5-6): 1157-67.
Liu T, Zhang Y, Shen Z, et al. Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived mesenchymal stem cells on rat kidney transplantation. Int J Mol Med 2017; 39(1): 144-52.
Nagata H, Ii M, Kohbayashi E, Hoshiga M, Hanafusa T, Asahi M. Cardiac adipose‐derived stem cells exhibit high differentiation potential to cardiovascular cells in C57BL/6 mice. Stem Cells Transl Med 2016; 5(2): 141-51.
Kondo K, Hayashida R, Shibata R, Murohara T. Therapeutic angiogenesis for critical limb ischemia by implantation of autologous adipose-derived regenerative cells: A clinical pilot study. Am Heart Assoc 2018. [Epub ahead of print]
Silvestre J-S, Planat-Benard V, Casteilla L. Adipose tissue-derived therapeutic cells for peripheral artery diseases: The fatty blessing. Expert Opin Biol Ther 2016; 16(6): 735-8.
Kim J-H, Joo HJ, Kim M, et al. Transplantation of adipose-derived stem cell sheet attenuates adverse cardiac remodeling in acute myocardial infarction. Tissue Eng Part A 2017; 23(1-2): 1-11.
Kim J-H, Hong SJ, Park C-Y, et al. Intramyocardial adipose-derived stem cell transplantation increases pericardial fat with recovery of myocardial function after acute myocardial infarction. PLoS One 2016; 11(6)e0158067
Wang B, Ma X, Zhao L, et al. Injection of basic fibroblast growth factor together with adipose-derived stem cell transplantation: Improved cardiac remodeling and function in myocardial infarction. Int J Clin Exp Med 2016; 16(4): 539-50.
Choi JY, Kim T-H, Yang JD, Suh JS, Kwon TG. Adipose-Derived regenerative cell injection therapy for postprostatectomy incontinence: a phase I clinical study. Yonsei Med J 2016; 57(5): 1152-8.
Gotoh M, Yamamoto T, Kato M, et al. Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose‐derived regenerative cells: 1‐year outcomes in 11 patients. Int J Urol 2014; 21(3): 294-300.
Chen X, Yang Q, Zheng T, et al. Neurotrophic effect of adipose tissue-derived stem cells on erectile function recovery by pigment epithelium-derived factor secretion in a rat model of cavernous nerve injury. Stem Cells Int 2016; 20165161248
Lu J, Xin Z, Zhang Q, et al. Beneficial effect of PEDF-transfected ADSCs on erectile dysfunction in a streptozotocin-diabetic rat model. Cell Tissue Res 2016; 366(3): 623-37.
Zhou F, Hui Y, Xin H, et al. Therapeutic effects of adipose-derived stem cells-based microtissues on erectile dysfunction in streptozotocin-induced diabetic rats. Asian J Androl 2017; 19(1): 91.
Lin H, Dhanani N, Tseng H, et al. Nanoparticle improved stem cell therapy for erectile dysfunction in a rat model of cavernous nerve injury. J Urol 2016; 195(3): 788-95.
Huang Y-C, Kuo Y-H, Huang Y-H, Chen C-S, Ho D-R, Shi C-S. The effects of adipose-derived stem cells in a rat model of tobacco-associated erectile dysfunction. PLoS One 2016; 11(6)e0156725
Jeon SH, Shrestha KR, Kim RY, et al. Combination therapy using human adipose-derived stem cells on the cavernous nerve and low-energy shockwaves on the corpus cavernosum in a rat model of post-prostatectomy erectile dysfunction. Urology 2016. 88: 226. e1-9.
Mahajan PV, Subramanian S, Danke A, Kumar A. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells. Case Repin Urol 2016; 20162539320
Tremp M, Salemi S, Largo R, et al. Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction. World J Urol 2014; 32(5): 1241-8.
Li J, Martin EC, Gimble JM. Adipose-Derived Stem/Stromal Cells Regenerative Medicine-from Protocol to Patient. Springer 2016; pp. 363-87.
Galipeau J, Sensébé L. Mesenchymal stromal cells: Clinical challenges and therapeutic opportunities. Cell Stem Cell 2018; 22(6): 824-33.
Ra JC, Shin IS, Kim SH, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev 2011; 20(8): 1297-308.
Herreros M, Garcia-Arranz M, Guadalajara H, De-La-Quintana P, Garcia-Olmo D. Autologous expanded adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistulas: a phase III randomized clinical trial (FATT 1: Fistula Advanced Therapy Trial 1) and long-term evaluation. Dis Colon Rectum 2012; 55(7): 762-72.
Pérez-Cano R, Vranckx J, Lasso J, et al. Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: The RESTORE-2 trial. Eur J Surg Oncol 2012; 38(5): 382-9.
Cho YB, Lee WY, Park KJ, Kim M, Yoo H-W, Yu CS. Autologous adipose tissue-derived stem cells for the treatment of Crohn’s fistula: a phase I clinical study. Cell Transplant 2013; 22(2): 279-85.
Bora P, Majumdar AS. Adipose tissue-derived stromal vascular fraction in regenerative medicine: A brief review on biology and translation. Stem Cell Res Ther 2017; 8(1): 145.
Perin EC, Sanz-Ruiz R, Sánchez PL, et al. Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: The PRECISE Trial. Am Heart J 2014; 168(1): 88-95. e2
Soong B, Lee O. Treatment of cerebellar ataxia with mesenchymal stem cells: a phase I/II trial. Cytotherapy 2014; 16(4): S17.
Dai R, Wang Z, Samanipour R, Koo K-I, Kim K. Adipose-derived stem cells for tissue engineering and regenerative medicine applications. Stem Cells Int 2016; 20166737345
Garcia-Olmo D, Guadalajara-Labajo H. Stem Cell Application in Fistula Disease Anal Fistula. Springer 2014; pp. 129-38.
Lim MH, Ong WK, Sugii S. The current landscape of adipose-derived stem cells in clinical applications. Expert Rev Mol Med 2014; 16.
Lee SY, Kim W, Lim C, Chung SG. Treatment of lateral epicondylosis by using allogeneic adipose‐derived mesenchymal stem cells: A pilot study. Stem Cells 2015; 33(10): 2995-3005.
Tissiani L, Alonso N. A prospective and controlled clinical trial on stromal vascular fraction enriched fat grafts in secondary breast reconstruction. Stem Cells Int 2016; 20162636454
Qayyum AA, Haack-Sørensen M, Mathiasen AB, Jørgensen E, Ekblond A, Kastrup J. Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial): Study design. Regen Med 2012; 7(3): 421-8.
Álvaro-Gracia JM, Jover JA, García-Vicuña R, et al. Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): Results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial. Ann Rheum Dis 2016; 76(1): 196-202.
Henry TD, Pepine CJ, Lambert CR, et al. The Athena trials: Autologous adipose‐derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction. Catheter Cardiovasc Interv 2017; 89(2): 169-77.
Dykstra JA, Facile T, Patrick RJ, et al. Concise review: Fat and furious: harnessing the full potential of adipose‐derived stromal vascular fraction. Stem Cells Transl Med 2017; 6(4): 1096-108.
Panés J, García-Olmo D, Van Assche G, et al. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn’s Disease. Gastroenterology 2018; 154(5): 1334-42.
del Barrio JLA, El Zarif M, de Miguel MP, et al. Cellular therapy with human autologous adipose-derived adult stem cells for advanced keratoconus. Cornea 2017; 36(8): 952-60.
Comella K, Silbert R, Parlo M. Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease. J Transl Med 2017; 15(1): 12.
Kastrup J, Schou M, Gustafsson I, et al. Rationale and design of the first double-blind, placebo-controlled trial with allogeneic adipose tissue-derived stromal cell therapy in patients with ischemic heart failure: A phase ii danish multicentre study. Stem Cells Int 2017; 20178506370
Kastrup J, Haack‐Sørensen M, Juhl M, et al. Cryopreserved off-the-shelf allogeneic adipose‐derived stromal cells for therapy in patients with ischemic heart disease and heart failure—a safety study. Stem Cells Transl Med 2017; 6(11): 1963-71.
Jo CH, Chai JW, Jeong EC, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: A 2-year follow-up study. Am J Sports Med 2017; 45(12): 2774-83.
Fernández O, Izquierdo G, Fernández V, Leyva L, Reyes V, Guerrero M, et al. Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study. PLoS One 2018; 13(5)e0195891
Jurado M, De La Mata C, Ruiz-García A, et al. Adipose tissue-derived mesenchymal stromal cells as part of therapy for chronic graft-versus-host disease: A phase I/II study. Cytotherapy 2017; 19(8): 927-36.
Dozois EJ, Lightner AL, Mathis KL, et al. Early results of a phase i trial using an adipose-derived mesenchymal stem cell-coated fistula plug for the treatment of transsphincteric cryptoglandular fistulas. Dis Colon Rectum 2019; 62(5): 615-22.

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Year: 2019
Page: [532 - 548]
Pages: 17
DOI: 10.2174/1574888X14666190411121528
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