{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:43:28Z","timestamp":1784911408018,"version":"3.55.0"},"reference-count":122,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T00:00:00Z","timestamp":1488844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Trauma may cause irreversible tissue damage and loss of function despite current best practice. Healing is dependent both on the nature of the injury and the intrinsic biological capacity of those tissues for healing. Preclinical research has highlighted stem cell therapy as a potential avenue for improving outcomes for injuries with poor healing capacity. Additionally, trauma activates the immune system and alters stem cell behaviour. This paper reviews the current literature on stem cells and its relevance to trauma care. Emphasis is placed on understanding how stem cells respond to trauma and pertinent mechanisms that can be utilised to promote tissue healing. Research involving notable difficulties in trauma care such as fracture non-union, cartilage damage and trauma induced inflammation is discussed further.<\/jats:p>","DOI":"10.3390\/ijms18030577","type":"journal-article","created":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T11:12:32Z","timestamp":1488885152000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Trauma and Stem Cells: Biology and Potential Therapeutic Implications"],"prefix":"10.3390","volume":"18","author":[{"given":"Kabilan","family":"Thurairajah","sequence":"first","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Department of Traumatology, John Hunter Hospital, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Broadhead","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Department of Traumatology, John Hunter Hospital, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Balogh","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Department of Traumatology, John Hunter Hospital, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.5694\/j.1326-5377.2008.tb02176.x","article-title":"A statewide system of trauma care in Victoria: Effect on patient survival","volume":"189","author":"Cameron","year":"2008","journal-title":"Med. J. Aust."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.injury.2008.06.034","article-title":"Improved trauma patient outcomes after implementation of a dedicated trauma admitting service","volume":"40","author":"Ursic","year":"2009","journal-title":"Injury"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.aenj.2011.12.001","article-title":"Traumatic injury in Australia and New Zealand","volume":"15","author":"Curtis","year":"2012","journal-title":"Australas. Emerg. Nurs. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1097\/00005373-199909001-00011","article-title":"Systematic review of trauma system effectiveness based on registry comparisons","volume":"47","author":"Jurkovich","year":"1999","journal-title":"J. Trauma"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0092-8674(00)81692-X","article-title":"Stem cells: Units of development, units of regeneration, and units in evolution","volume":"100","author":"Weissman","year":"2000","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1146\/annurev.cellbio.21.012704.131525","article-title":"Stem cell niche: Structure and function","volume":"21","author":"Li","year":"2005","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.2741\/3853","article-title":"Mesenchymal stem cells and their microenvironment","volume":"16","author":"Schraufstatter","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nri1779","article-title":"Bone-marrow haematopoietic-stem-cell niches","volume":"6","author":"Wilson","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1038\/nature09229","article-title":"Nuclear reprogramming to a pluripotent state by three approaches","volume":"465","author":"Yamanaka","year":"2010","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature04955","article-title":"Nuclear reprogramming and pluripotency","volume":"441","author":"Hochedlinger","year":"2006","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6289825","DOI":"10.1155\/2016\/6289825","article-title":"Mesenchymal Stem Cells after Polytrauma: Actor and Target","volume":"2016","author":"Wiegner","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nbt.2816","article-title":"Mesenchymal stem cells: Immune evasive, not immune privileged","volume":"32","author":"Ankrum","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"132","DOI":"10.2302\/kjm.54.132","article-title":"Multipotential differentiation of adipose tissue-derived stem cells","volume":"54","author":"Strem","year":"2005","journal-title":"Keio J. Med."},{"key":"ref_14","first-page":"747","article-title":"Mesenchymal stem cells: A new trend for cell therapy","volume":"34","author":"Wei","year":"2013","journal-title":"Chung Kuo Yao Li Hsueh Pao"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00441-012-1393-9","article-title":"Mechanisms of action of mesenchymal stem cells in cutaneous wound repair and regeneration","volume":"348","author":"Li","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1073\/pnas.89.7.2804","article-title":"Isolation of a candidate human hematopoietic stem-cell population","volume":"89","author":"Baum","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/stem.418","article-title":"Bone marrow-derived hematopoietic cells undergo myogenic differentiation following a Pax-7 independent pathway","volume":"28","author":"Xynos","year":"2010","journal-title":"Stem Cells"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/scrt54","article-title":"Mobilization of hematopoietic stem cells from the bone marrow niche to the blood compartment","volume":"2","author":"Hoggatt","year":"2011","journal-title":"Stem Cell Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1097\/SCS.0b013e3182902779","article-title":"Comparison of chondrocytes produced from adipose tissue-derived stem cells and cartilage tissue","volume":"24","author":"Meric","year":"2013","journal-title":"J. Craniofac. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1111\/wrr.12080","article-title":"Adipose tissue-derived stem cells (ADSCs) transplantation promotes regeneration of expanded skin using a tissue expansion model","volume":"21","author":"Sheng","year":"2013","journal-title":"Wound Repair Regen."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1126\/science.275.5302.964","article-title":"Isolation of putative progenitor endothelial cells for angiogenesis","volume":"275","author":"Asahara","year":"1997","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1089\/neu.2006.0180","article-title":"Trauma-associated inflammatory response impairs embryonic stem cell survival and integration after implantation into injured rat brain","volume":"24","author":"Molcanyi","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R118","DOI":"10.1186\/cc7968","article-title":"The change and effect of endothelial progenitor cells in pig with multiple organ dysfunction syndromes","volume":"13","author":"Luo","year":"2009","journal-title":"Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1097\/01.sla.0000094441.38807.09","article-title":"Bone marrow failure following severe injury in humans","volume":"238","author":"Livingston","year":"2003","journal-title":"Ann. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"833","DOI":"10.2217\/rme.12.82","article-title":"Stem cell recruitment after injury: Lessons for regenerative medicine","volume":"7","author":"Rennert","year":"2012","journal-title":"Regen Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.jcyt.2013.02.009","article-title":"CXCR4 transfection of cord blood mesenchymal stromal cells with the use of cationic liposome enhances their migration toward stromal cell-derived factor-1","volume":"15","author":"Xu","year":"2013","journal-title":"Cytotherapy"},{"key":"ref_27","first-page":"561098","article-title":"Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1\/CXCR4 axis","volume":"2013","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1524-475X.2009.00454.x","article-title":"Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-alpha and its possible role in wound healing","volume":"17","author":"Fu","year":"2009","journal-title":"Wound Repair Regen."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/scd.2006.0032","article-title":"Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells","volume":"16","author":"Ozaki","year":"2007","journal-title":"Stem Cells Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S94","DOI":"10.1016\/S0020-1383(10)70018-8","article-title":"Randomized prospective clinical trial comparing reamer irrigator aspirator (RIA) to standard reaming (SR) in both minimally injured and multiply injured patients with closed femoral shaft fractures treated with reamed intramedullary nailing (IMN)","volume":"41","author":"Hartsock","year":"2010","journal-title":"Injury"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/01.TA.0000075787.69695.4E","article-title":"Impact of intramedullary instrumentation versus damage control for femoral fractures on immunoinflammatory parameters: Prospective randomized analysis by the EPOFF Study Group","volume":"55","author":"Pape","year":"2003","journal-title":"J. Trauma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1111\/j.1537-2995.2009.02335.x","article-title":"Thrombin generation in trauma patients","volume":"49","author":"Dunbar","year":"2009","journal-title":"Transfusion"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ritz, U., Spies, V., Mehling, I., Gruszka, D., Rommens, P.M., and Hofmann, A. (2014). Mobilization of CD34+-progenitor cells in patients with severe trauma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097369"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/SHK.0b013e3182236eba","article-title":"Trauma-activated polymorphonucleated leukocytes damage endothelial progenitor cells: Probable role of CD11b\/CD18-CD54 interaction and release of reactive oxygen species","volume":"36","author":"Henrich","year":"2011","journal-title":"Shock"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1097\/HJH.0b013e328329e31c","article-title":"Early lipopolysaccharide-induced reactive oxygen species production evokes necrotic cell death in human umbilical vein endothelial cells","volume":"27","author":"Simon","year":"2009","journal-title":"J. Hypertens."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"719","DOI":"10.2353\/ajpath.2006.060042","article-title":"NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes","volume":"169","author":"Ebrahimian","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/iwj.12039","article-title":"Acute and chronic wound fluids inversely influence adipose-derived stem cell function: Molecular insights into impaired wound healing","volume":"12","author":"Koenen","year":"2015","journal-title":"Int. Wound J."},{"key":"ref_38","unstructured":"R\u00fcedi, T.P., and Murphy, W.M. (2000). AO Principles of Fracture Management, Thieme."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1089\/ten.tec.2013.0465","article-title":"Evaluation of native mesenchymal stem cells from bone marrow and local tissue in an atrophic nonunion model","volume":"20","author":"Tawonsawatruk","year":"2014","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.jcyt.2013.05.004","article-title":"Mobilization of endogenous stem cell populations enhances fracture healing in a murine femoral fracture model","volume":"15","author":"Toupadakis","year":"2013","journal-title":"Cytotherapy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1002\/stem.103","article-title":"Regenerative effects of transplanted mesenchymal stem cells in fracture healing","volume":"27","author":"Weis","year":"2009","journal-title":"Stem Cells"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bone.2014.09.017","article-title":"Bringing new life to damaged bone: The importance of angiogenesis in bone repair and regeneration","volume":"70","author":"Stegen","year":"2015","journal-title":"Bone"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/jor.21083","article-title":"Endothelial progenitor cells promote fracture healing in a segmental bone defect model","volume":"28","author":"Atesok","year":"2010","journal-title":"J. Orthop. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.2353\/ajpath.2006.060064","article-title":"Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing","volume":"169","author":"Matsumoto","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1089\/ten.tea.2013.0314","article-title":"Long-term tracking of segmental bone healing mediated by genetically engineered adipose-derived stem cells: Focuses on bone remodeling and potential side effects","volume":"20","author":"Lin","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/stem.1945","article-title":"Role of muscle stem cells during skeletal regeneration","volume":"33","author":"Yang","year":"2015","journal-title":"Stem Cells"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1007\/s10439-008-9629-2","article-title":"Pressure and distortion regulate human mesenchymal stem cell gene expression","volume":"37","author":"Haudenschild","year":"2009","journal-title":"Ann. Biomed. Eng."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1007\/s10439-010-9979-4","article-title":"Tensile strain as a regulator of mesenchymal stem cell osteogenesis","volume":"38","author":"Kearney","year":"2010","journal-title":"Ann. Biomed. Eng."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/03008207.2011.619284","article-title":"Effect of mechanical stimulation on the differentiation of cord stem cells","volume":"53","author":"Kang","year":"2012","journal-title":"Connect. Tissue Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10330","DOI":"10.1074\/jbc.M113.546382","article-title":"Low intensity pulsed ultrasound (LIPUS) influences the multilineage differentiation of mesenchymal stem and progenitor cell lines through ROCK-Cot\/Tpl2-MEK-ERK signaling pathway","volume":"289","author":"Kusuyama","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1089\/ten.tea.2014.0035","article-title":"Infrapatellar fat pad-derived stem cells maintain their chondrogenic capacity in disease and can be used to engineer cartilaginous grafts of clinically relevant dimensions","volume":"20","author":"Liu","year":"2014","journal-title":"Tissue Eng. Part A"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/j.1365-2184.2007.00461.x","article-title":"Simulated microgravity inhibits the proliferation and osteogenesis of rat bone marrow mesenchymal stem cells","volume":"40","author":"Dai","year":"2007","journal-title":"Cell Prolif."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s007740050081","article-title":"Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation","volume":"17","author":"Nishida","year":"1999","journal-title":"J. Bone Miner. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1136\/jcp.55.9.693","article-title":"Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis","volume":"55","author":"Verma","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.2106\/JBJS.L.01502","article-title":"Wnt3a reestablishes osteogenic capacity to bone grafts from aged animals","volume":"95","author":"Leucht","year":"2013","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"519028","DOI":"10.4061\/2010\/519028","article-title":"Mesenchymal Progenitor Cells and Their Orthopedic Applications: Forging a Path towards Clinical Trials","volume":"2010","author":"Shenaq","year":"2010","journal-title":"Stem Cells Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/mt.2013.109","article-title":"Stem cell-based therapy for prevention of delayed fracture union: A randomized and prospective preliminary study","volume":"21","author":"Liebergall","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"128","DOI":"10.5966\/sctm.2013-0106","article-title":"Local transplantation of granulocyte colony stimulating factor-mobilized CD34+ cells for patients with femoral and tibial nonunion: Pilot clinical trial","volume":"3","author":"Kuroda","year":"2014","journal-title":"Stem Cells Transl."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1002\/art.30234","article-title":"Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo","volume":"63","author":"Kurth","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.joca.2011.05.003","article-title":"The relationship between fibrogenic TGFbeta1 signaling in the joint and cartilage degradation in post-injury osteoarthritis","volume":"19","author":"Plaas","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1002\/jor.21215","article-title":"Knockout of ADAMTS5 does not eliminate cartilage aggrecanase activity but abrogates joint fibrosis and promotes cartilage aggrecan deposition in murine osteoarthritis models","volume":"29","author":"Li","year":"2011","journal-title":"J. Orthop. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"26016","DOI":"10.1074\/jbc.M110.208694","article-title":"Adamts5 Deletion Blocks Murine Dermal Repair through CD44-mediated Aggrecan Accumulation and Modulation of Transforming Growth Factor \u03b21 (TGF\u03b21) Signaling","volume":"286","author":"Velasco","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.3727\/096368912X653264","article-title":"Intra-articular delivery of purified mesenchymal stem cells from C57BL\/6 or MRL\/MpJ superhealer mice prevents posttraumatic arthritis","volume":"22","author":"Diekman","year":"2013","journal-title":"Cell Transpl."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"23076","DOI":"10.1038\/srep23076","article-title":"Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model","volume":"6","author":"Mak","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1634\/stemcells.2005-0319","article-title":"Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors","volume":"24","author":"Honczarenko","year":"2006","journal-title":"Stem Cells"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.arthro.2012.12.008","article-title":"Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial","volume":"29","author":"Saw","year":"2013","journal-title":"Arthroscopy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1097\/TP.0000000000000167","article-title":"Treatment of knee osteoarthritis with autologous mesenchymal stem cells: Two-year follow-up results","volume":"97","author":"Orozco","year":"2014","journal-title":"Transplantation"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"90","DOI":"10.2106\/JBJS.M.00058","article-title":"Adult Human Mesenchymal Stem Cells Delivered via Intra-Articular Injection to the Knee Following Partial Medial Meniscectomy. A Randomized, Double-Blind, Controlled Study","volume":"96","author":"Vangsness","year":"2014","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_69","first-page":"117","article-title":"Mesenchymal stem cell therapy for osteoarthritis: Current perspectives","volume":"8","author":"Wyles","year":"2015","journal-title":"Stem Cells Cloning"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1186\/s12891-016-1085-9","article-title":"Mesenchymal stem cell therapy in the treatment of osteoarthritis: Reparative pathways, safety and efficacy\u2014A review","volume":"17","author":"Freitag","year":"2016","journal-title":"BMC Musculoskelet. Disord."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1517\/14712598.2016.1145651","article-title":"Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair","volume":"16","author":"Reissis","year":"2016","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Waterman, R.S., Tomchuck, S.L., Henkle, S.L., and Betancourt, A.M. (2010). A New Mesenchymal Stem Cell (MSC) Paradigm: Polarization into a Pro-Inflammatory MSC1 or an Immunosuppressive MSC2 Phenotype. PLoS ONE.","DOI":"10.1371\/journal.pone.0010088"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1182\/blood-2006-06-028704","article-title":"Toll-like receptors and their ligands control mesenchymal stem cell functions","volume":"109","author":"Morad","year":"2007","journal-title":"Blood"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bbrc.2014.04.097","article-title":"Priming of Toll-like receptor 4 pathway in mesenchymal stem cells increases expression of B cell activating factor","volume":"448","author":"Yan","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1016\/j.yexcr.2010.05.024","article-title":"Toll-like receptor 9 ligands enhance mesenchymal stem cell invasion and expression of matrix metalloprotease-13","volume":"316","author":"Nurmenniemi","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/TA.0000000000000519","article-title":"Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery","volume":"78","author":"McIlroy","year":"2015","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nm.1905","article-title":"Bone marrow stromal cells attenuate sepsis via prostaglandin E-dependent reprogramming of host macrophages to increase their interleukin-10 production","volume":"15","author":"Nemeth","year":"2009","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nm.2736","article-title":"Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury","volume":"18","author":"IIslam","year":"2012","journal-title":"Nat. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1097\/TA.0b013e3182703420","article-title":"Autologous transplantation of endothelial progenitor cells to prevent multiple organ dysfunction syndromes in pig","volume":"74","author":"Tianhang","year":"2013","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jamcollsurg.2012.08.028","article-title":"The Role of Plasma G-CSF and Bone Marrow Dysfunction after Severe Trauma","volume":"216","author":"Cook","year":"2013","journal-title":"J. Am. Coll. Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/ni813","article-title":"G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4","volume":"3","author":"Petit","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1097\/TA.0000000000000823","article-title":"Mesenchymal Stem Cells Reverse Bone Marrow Dysfunction Following Injury and Stress","volume":"79","author":"Gore","year":"2015","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.jss.2015.06.023","article-title":"Mesenchymal stem cells reverse trauma and hemorrhagic shock-induced bone marrow dysfunction","volume":"199","author":"Gore","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/ALN.0000000000000545","article-title":"Therapeutic efficacy of human mesenchymal stromal cells in the repair of established ventilator-induced lung injury in the rat","volume":"122","author":"Hayes","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e319","DOI":"10.1097\/CCM.0b013e31828a663e","article-title":"Effects of mesenchymal stem cell therapy on the time course of pulmonary remodeling depend on the etiology of lung injury in mice","volume":"41","author":"Silva","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000047856","article-title":"The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion","volume":"169","author":"Gao","year":"2001","journal-title":"Cells Tissues Organs"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/ALN.0000000000000546","article-title":"Mesenchymal Stem Cell Therapy for Acute Respiratory Distress Syndrome: A Light at the End of the Tunnel?: Optimizing Therapeutic Potential of Human Mesenchymal Stromal Cells to Enhance Repair following Ventilator Induced Lung Injury in the Rat","volume":"122","author":"Hayes","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S2213-2600(14)70291-7","article-title":"Mesenchymal stem (stromal) cells for treatment of ARDS: A phase 1 clinical trial","volume":"3","author":"Wilson","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"142","DOI":"10.5966\/sctm.2011-0018","article-title":"Concise review: Role of mesenchymal stem cells in wound repair","volume":"1","author":"Maxson","year":"2012","journal-title":"Stem Cells Transl. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"831095","DOI":"10.1155\/2015\/831095","article-title":"Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential","volume":"2015","author":"Isakson","year":"2015","journal-title":"Stem Cells Int."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1590\/abd1806-4841.20142530","article-title":"Stem cells in dermatology","volume":"89","author":"Ogliari","year":"2014","journal-title":"Anais Brasileiros de Dermatologia"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1089\/rej.2010.1050","article-title":"Interactive role of trauma cytokines and erythropoietin and their therapeutic potential for acute and chronic wounds","volume":"14","author":"Bader","year":"2011","journal-title":"Rejuvenation Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/wrr.12278","article-title":"Effects of VEGF and MSCs on vascular regeneration in a trauma model in rats","volume":"23","author":"Niyaz","year":"2015","journal-title":"Wound Repair Regen."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1634\/stemcells.2007-0226","article-title":"Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis","volume":"25","author":"Wu","year":"2007","journal-title":"Stem Cells"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jdermsci.2007.05.018","article-title":"Wound healing effect of adipose-derived stem cells: A critical role of secretory factors on human dermal fibroblasts","volume":"48","author":"Kim","year":"2007","journal-title":"J. Dermatol. Sci."},{"key":"ref_96","first-page":"349","article-title":"Long-term outcome of acellular dermal matrix when used for large traumatic open abdomen","volume":"65","author":"Dunham","year":"2008","journal-title":"J. Trauma"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/term.1622","article-title":"Targeted delivery of adipose-derived stem cells via acellular dermal matrix enhances wound repair in diabetic rats","volume":"9","author":"Nie","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/wrr.12251","article-title":"MSCs seeded on bioengineered scaffolds improve skin wound healing in rats","volume":"23","author":"Formigli","year":"2015","journal-title":"Wound Repair Regen."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.9.2.493","article-title":"Satellite cell of skeletal muscle fibers","volume":"9","author":"Mauro","year":"1961","journal-title":"J. Biophys. Biochem. Cytol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cell.2007.03.044","article-title":"Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in Muscle","volume":"129","author":"Kuang","year":"2007","journal-title":"Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"822","DOI":"10.2106\/00004623-200205000-00022","article-title":"Muscle injuries and repair: Current trends in research","volume":"84","author":"Huard","year":"2002","journal-title":"J. Bone Joint Surg. Am."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0002-9440(10)63188-4","article-title":"Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: A key event in muscle fibrogenesis","volume":"164","author":"Li","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S0002-9440(10)64250-2","article-title":"Differentiation of Muscle-Derived Cells into Myofibroblasts in Injured Skeletal Muscle","volume":"161","author":"Li","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s00018-014-1819-5","article-title":"Stem cell activation in skeletal muscle regeneration","volume":"72","author":"Fu","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1136\/bjsm.2006.028639","article-title":"Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury","volume":"40","author":"Lucia","year":"2006","journal-title":"Br. J. Sports Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"12601","DOI":"10.1074\/jbc.R200027200","article-title":"The basement membrane\/basal lamina of skeletal muscle","volume":"278","author":"Sanes","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.1111\/febs.12372","article-title":"Lying low but ready for action: The quiescent muscle satellite cell","volume":"280","author":"Montarras","year":"2013","journal-title":"FEBS J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.genm.2012.01.007","article-title":"Mesenchymal stem cell therapy following muscle trauma leads to improved muscular regeneration in both male and female rats","volume":"9","author":"Duda","year":"2012","journal-title":"Gend Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"s60","DOI":"10.1002\/term.1542","article-title":"Immediate and delayed transplantation of mesenchymal stem cells improve muscle force after skeletal muscle injury in rats","volume":"6","author":"Winkler","year":"2012","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1161\/01.CIR.0000157144.24888.7E","article-title":"Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via \u201cimported\u201d nitric oxide synthase activity","volume":"111","author":"Ii","year":"2005","journal-title":"Circulation"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1182\/blood.V92.2.362","article-title":"Evidence for circulating bone marrow-derived endothelial cells","volume":"92","author":"Shi","year":"1998","journal-title":"Blood"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1161\/01.RES.87.9.728","article-title":"Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation","volume":"87","author":"Crosby","year":"2000","journal-title":"Circ. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"10931","DOI":"10.1016\/S0021-9258(19)49853-0","article-title":"Angiogenesis","volume":"267","author":"Folkman","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.yjmcc.2005.07.003","article-title":"Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells","volume":"39","author":"Urbich","year":"2005","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1182\/blood-2007-03-078709","article-title":"Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA","volume":"110","author":"Deregibus","year":"2007","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1161\/01.CIR.0000121425.42966.F1","article-title":"Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells","volume":"109","author":"Rehman","year":"2004","journal-title":"Circulation"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1161\/01.CIR.0000135466.16823.D0","article-title":"Improvement of postnatal neovascularization by human adipose tissue-derived stem cells","volume":"110","author":"Miranville","year":"2004","journal-title":"Circulation"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1111\/j.1743-6109.2012.02827.x","article-title":"The Therapeutic Role of VEGF-Expressing Muscle-Derived Stem Cells in Acute Penile Cavernosal Injury","volume":"9","author":"An","year":"2012","journal-title":"J. Sex. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/wrr.12395","article-title":"Wound healing society 2014 update on guidelines for arterial ulcers","volume":"24","author":"Federman","year":"2016","journal-title":"Wound Repair Regen."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1159\/000381877","article-title":"Stem Cells in Wound Healing: The Future of Regenerative Medicine? A Mini-Review","volume":"62","author":"Duscher","year":"2016","journal-title":"Gerontology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13287-016-0303-6","article-title":"Mesenchymal stem cells and cutaneous wound healing: Novel methods to increase cell delivery and therapeutic efficacy","volume":"7","author":"Agrawal","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"229","DOI":"10.4103\/0970-0358.101285","article-title":"An update review of stem cell applications in burns and wound care","volume":"45","author":"Huang","year":"2012","journal-title":"Indian J. Plast. Surg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/3\/577\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:29:54Z","timestamp":1760207394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/3\/577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,7]]},"references-count":122,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["ijms18030577"],"URL":"https:\/\/doi.org\/10.3390\/ijms18030577","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,7]]}}}