Clinical application of AD-MSCs – A review
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Polish Stem Cell Bank,Warsaw, Poland
Clinic of Paediatric Neurology, III Faculty of Paediatrics, Medical Univercity of Lublin
Ekaterina Semenova   

Polish Stem Cell Bank, Dzialkowa 85, 02-234 Warsaw, Poland
J Pre Clin Clin Res. 2018;12(3):100–105
Mesenchymal stromal/stem cells (MSCs) are a unique type of stem cell which can be successfully used in regenerative medicine. They are safe, have the ‘stem cell’ ability of self-renewal and under appropriate conditions can differentiate into other types of cells without the problem of teratoma formation. MSCs express the characteristic phenotype (CD73ᶧ, CD90ᶧ, CD105ᶧ, CD14⁻, CD19⁻, CD34⁻, CD45⁻, HLA-DR⁻) and show immunosuppressive features, such as low expression of MHC I, lack of MHC II and secretion of a wide variety of immunoprotective cytokines and growth factors. One of the MSC sources is adipose tissue, which has some advantages compared with other existing sources. Currently, adipose tissue as a source of mesenchymal stromal/stem cells have become of interest due to a less invasive procedure of isolation and safety. This review contains data from various studies about the usage of adipose-derived MSCs in the treatment of different diseases.

The main aim of this review is evaluation of the useful characteristics of adipose-derived mesenchymal stem cells and their usage in stem cell treatment of some diseases. The aim is to describe the current knowledge and future perspectives.

Adipose-derived MSCs (AD-MSCs) represent a good tool in regenerative stem cell therapy.

Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976; 4: 267.
Kmiecik G, Niklinska W, Kuc P, Pancewicz-Wojtkiewicz J, Fil D, et al. Fetal membranes as a source of stem cells. Adv Med Sci. 58: 185–95.
Marcus AJ, Woodbury D. Fetal stem cells from extra-embryonic tissues: Do not discard. J Cell Mol Med. 2008; 12: 730–42.
Horwitz EM, Gordon PL, Koo WK, et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci USA. 2002; 99: 8932–8937.
Wakitani S, Nawata M, Tensho K, et al. Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees. J Tissue Eng Regen Med. 2007; 1: 74–79.
Baron F, Lechanteur C, Willems E, et al. Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2010; 16: 838–847.
Shridharani SM, Broyles JM, Matarasso A. Liposuction devices: technology update. Med Devices (Auckl). 2014; 7: 241–251.
Cawthorn WP, Scheller EL, MacDougald OA. Adipose tissue stem cells meet preadipocyte commitment: going back to the future. J Lipid Res. 2012; 53(2): 227–46.
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: 376–385.
Brzoska M, Geiger H, Gauer S, Baer P. Epithelial differentiation of human adipose tissue-derived adult stem cells. Biochem Biophys Res Commun. 2005; 330(1): 142–50.
Grasys J, Kim BS, Pallua N. Content of Soluble Factors and Characteristics of Stromal Vascular Fraction Cells in Lipoaspirates from Different Subcutaneous Adipose Tissue Depots. Aesthet Surg J. 2016; 36: 831–841.
Yoshimura K, Asano Y, Aoi N, et al. Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J. 2010; 16(2): 169–75.
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.
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: 315–317.
Rehman J, Traktuev D, Li J, et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004; 109: 1292–8.
Song SY, Chung HM, Sung JH. The pivotal role of VEGF in adipose-derived-stem-cell-mediated regeneration. Expert Opin Biol Ther. 2010; 10: 1529–1537.
Seo MJ, Suh SY, Bae YC, Jung JS. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun. 2005; 328: 258–264.
Tsuji W, Rubin JP, Marra KG. Adipose-derived stem cells: Implications in tissue regeneration. World J Stem Cells. 2014; 26; 6(3): 312–321.
Salgado AJ, Reis RL, Sousa NJ, Gimble JM. Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther. 2010; 5(2): 103–10.
Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F. Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther. 2008; 15(10): 730–8.
Bhutani S, Vishwanath G. Hyperbaric oxygen and wound healing. Indian J. Plast Surg. 2012; 45(2): 316–324.
Han G, Ceilley R. Chronic Wound Healing: A Review of Current Management and Treatments. Adv. Ther. 2017; 34(3): 599–610.
Kato T, Khanh VC, Sato K, Takeuchi K, et al. SDF-1 improves wound healing ability of glucocorticoid-treated adipose tissue-derived mesenchymal stem cells. Biochem Biophys Res Commun. 2017; 493(2): 1010–1017.
Wang M, Crisostomo PR, Herring C, et al. Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2006; 291: R880–4.
Ebrahimian TG, Pouzoulet F, Squiban C, et al. Cell therapy based on adipose tissue derived stromal cells promotes physiological and pathological wound healing. Arterioscler Thromb Vasc Biol. 2009; 29: 503–10.
Huang SP, Huang CH, Shyu JF, et al. Promotion of wound healing using adipose-derived stem cells in radiation ulcer of a rat model. Journal of Biomedical Science. 2013; 20(1): 51.
Turner NJ, Badylak SF. The Use of Biologic Scaffolds in the Treatment of Chronic Nonhealing Wounds. Adv Wound Care (New Rochelle). 2015; 4(8): 490–500.
Dickinson LE, Gerecht S. Engineered Biopolymeric Scaffolds for Chronic Wound Healing Front Physiol. 2016; 5(7): 341.
Kuo YR, Wang CT, Cheng JT, et al. Adipose-derived stem cells accelerate diabetic wound healing through the induction of autocrine and paracrine effects. Cell Transplant. 2016; 25: 71–81.
Marconi S, Castiglione G, Turano E, et al. Human Adipose-Derived Mesenchymal Stem Cells Systemically Injected Promote Peripheral Nerve Regeneration in the Mouse Model of Sciatic Crush. Tissue Engineering. 2012; 18: 11–12.
Lopatina T, Kalinina N, Karagyaur M, et al. Adipose-derived stem cells stimulate regeneration of peripheral nerves: BDNF secreted by these cells promotes nerve healing and axon growth de novo. PLoS One. 2011; 6: e17899.
Matthes SM, Reimers K, Janssen I, et al. Intravenous transplantation of mesenchymal stromal cells to enhance peripheral nerve regeneration. Biomed Res Int. 2013; 2013: 573169.
Fairbairn NG, Meppelink AM, Ng-Glazier J, Randolph MA, Winograd JM. Augmenting peripheral nerve regeneration using stem cells: A review of current opinion. World J Stem Cells. 2015; 7: 11–26.
Liao T, Moussallem MD, Kim J, Schlenoff JB, Ma T. N-isopropylacrylamide-based thermoresponsive polyelectrolyte multilayer films for human mesenchymal stem cell expansion. Biotechnol Prog. 2010; 26(6): 1705–13.
Dai LG, Huang GS, Hsu SH. Sciatic nerve regeneration by cocultured Schwann cells and stem cells on microporous nerve conduits. Cell Transplant. 2013; 22(11): 2029–39.
Kingham PJ, Kalbermatten DF, Mahay D, Armstrong SJ, Wiberg M, Terenghi G. Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp. Neurol. 2007; 207(2): 267–274.
Wei Y, Gong K, Zheng Z, et al. Schwann-like cell differentiation of rat adipose-derived stem cells by indirect coculture with Schwann cells in vitro. Cell Prolif. 2010; 43(6): 606–616.
Luo H, Zhang Y, Zhang Z, Jin Y. The protection of MSCs from apoptosis in nerve regeneration by TGFβ1 through reducing inflammation and promoting VEGF-dependent angiogenesis. Biomaterials. 2012; 33(17): 4277–87.
Denker AE, Nicoll SB, Tuan RS. Formation of cartilage-like spheroids by micromass cultures of murine C3H10T1/2 cells upon treatment with transforming growth factor-beta 1. Differentiation. 1995; 59: 25–34.
Yoon IS, Chung CW, Sung JH, et al. Proliferation and chondrogenic differentiation of human adipose-derived mesenchymal stem cells in porous hyaluronic acid scaffold. Journal of Bioscience and Bioengineering 2011; 112: 402–408.
Dragoo JL, Carlson G, McCormick F, et al. Healing full-thickness cartilage defects using adipose-derived stem cells. Tissue Engineering. 2007; 13: 1615–1621.
Leslie SK, Cohen DJ, Sedlaczek J, et al. Controlled release of rat adipose-derived stem cells from alginate microbeads. Biomaterials. 2013; 34: 8172–8184.
Lin Y, Luo E, Chen X, et al. Molecular and cellular characterization during chondrogenic differentiation of adipose tissue-derived stromal cells in vitro and cartilage formation in vivo. Journal of Cellular and Molecular Medicine. 2005; 9: 929–939.
Estes BT, Wu AW, Guilak F. Potent induction of chondrocytic differentiation of human adipose-derived adult stem cells by bone morphogenetic protein 6. Arthritis and Rheumatism. 2006; 54: 1222–1232.
Hoekstra A. Prospering on the Fat of the Land: Adipose-derived stem cells as an industrially-viable resource for regenerative treatment. MMG 445 Basic Biotechnology. 2011; 7: 24–30.
Lendeckel S, Jodicke A, Christophis P, et al. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. J Cranio-Maxillo-Facial Surg. 2004; 32: 370–3.
Thesleff T, Lehtimaki K, Niskakangas T, et al. Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction. Neurosurgery. 2011; 68: 1535–40.
Sandor GK, Tuovinen VJ, Wolff J, et al. Adipose stem cell tissue-engineered construct used to treat large anterior mandibular defect: a case report and review of the clinical application of good manufacturing practice-level adipose stem cells for bone regeneration. J Oral Maxillofac Surg. 2013; 71: 938–50.
Yoshimura K, Eto H, Kato H, et al. In vivo manipulation of stem cells for adipose tissue repair/reconstruction. Regen Med. 2011; 6: 33–41.
Moseley TA, Zhu M, Hedrick MH. Adipose-derived stem and progenitor cells as fillers in plastic and reconstructive surgery. Plastic and Reconstructive Surgery. 2006; 118: 121S–128S.
Lee SK, Kim DW, Dhong ES, et al. Facial Soft Tissue Augmentation using Autologous Fat Mixed with Stromal Vascular Fraction. Archivial Plastic Surgery. 2012; 39: 534–539.
Zhou BR, Zhang T, Bin Jameel AA, et al. The efficiency of conditioned media of adipose-derived stem cells combined with ablative carbon dioxide fractional resurfacing for atrophic acne scars and skin rejuvenation. J Cosmet Laser Нer. 2016; 18: 138–148.
Meruane MA, Rojas M, Marcelain K. The use of adipose tissue-derived stem cells within a dermal substitute improves skin regeneration by increasing neoangiogenesis and collagen synthesis. Plast Reconstr Surg. 2012; 130(1): 53–63.
Salahat MA, LA Hadid. Autologous Adipose Stem Cells Use for Skin Regeneration and Treatment in Humans. J Biol Agr and Health. 2013; 3(1).
Mahajan PV, Subramanian S, Parab SC, et al. Regenerative Medicine Using Platelet Rich Plasma and Stem Cells in Atrophic Acne Scars: A Case Report. J Cosmo Trichol. 2017; 3: 2.
Vegiopoulos A, Müller-Decker K, Strzoda D, et al. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 2010; 328(5982): 1113–1114.
Ye J, Gao Z, Yin J, et al. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab. 2007; 293: E1118–E1128.
Louwen F, Ritter A, Kreis NN, Yuan J. Insight into the development of obesity: functional alterations of adipose-derived mesenchymal stem cells. Obes Rev. 2018; 19(7): 888–904.
Cao Y. Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov. 2010; 9(2): 107–15.
Cao Y. Angiogenesis as a therapeutic target for obesity and metabolic diseases. Chem Immunol Allergy. 2014; 99: 170–9.
Brakenhielm E, Cao Y. Angiogenesis in adipose tissue. Methods Mol Biol. 2008; 456: 65–81.
Cao Y. Angiogenesis modulates adipogenesis and obesity. J Clin Invest. 2007; 117(9): 2362–2368.
Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006; 290: H560–H576.
Sterodimas A, de Faria J, Nicaretta B, Pitanguy I. Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. J Plast Reconstr Aesthet Surg. 2010; 63(11): 1886–1892.
Robey P. “Mesenchymal stem cells”: fact or fiction, and implications in their therapeutic use. F1000Research. 2017; 6(F1000 Faculty Rev): 524.