title: Bone marrow stromal cells in a liquid fibrin matrix improve the healing process of patellar tendon window defects.
abstract: Following injury, ligaments and tendons do not regain their normal biological and biomechanical status. This study analyzed whether an injection of human bone marrow stromal cells (BMSC) or human fibroblast in a liquid fibrin matrix influences the histological results, ultrastructural morphology, mRNA expression of essential extracellular matrix proteins, and material properties of the healing tissue. Standardized full-thickness, full-length defects of the central portion of patellar tendons were created in 96 immunodeficient rats, and filled with human BMSC in a fibrin matrix (BMSC group), human fibroblasts in a fibrin matrix (fibroblast group), or fibrin matrix only (matrix group), or left untreated (defect group). Histological sections revealed more mature tissue formation with more regular patterns of cell distribution in the BMSC group, without signs of ectopic tissue formation into bone or cartilage. Mean collagen fibril diameter and relative area covered by collagen fibrils were significantly higher at 10 and 20 days postoperatively in the BMSC group compared to the defect and matrix groups, and comparable to normal tendon tissue. Further, collagen I mRNA expression, collagen I/collagen III mRNA ratio, and Young's modulus were significantly increased at 20 days postoperatively in comparison to the defect and matrix groups. In the fibroblast group, only mean collagen fibril diameter was significantly higher compared to the defect group, whereas the other biological and biomechanical parameters were not significantly improved. This study reveals that an injection of BMSC in a liquid fibrin matrix stimulates histological, ultrastructural, molecular biologic, and biomechanical parameters of patellar tendon healing, whereas injection of fibroblasts in fibrin matrix had only minor effects on the stimulation of tendon healing.
authors.affiliation: Department of Trauma, Hanover Medical School (MHH), Hanover, Germany. hankemeier.stefan@mh-hannover.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Hankemeier
authors.forename: Christof
authors.initials: C
authors.lastname: Hurschler
authors.forename: Johannes
authors.initials: J
authors.lastname: Zeichen
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
authors.forename: Brian
authors.initials: B
authors.lastname: Miller
authors.forename: Rupert
authors.initials: R
authors.lastname: Meller
authors.forename: Marco
authors.initials: M
authors.lastname: Ezechieli
authors.forename: Christian
authors.initials: C
authors.lastname: Krettek
authors.forename: Michael
authors.initials: M
authors.lastname: Jagodzinski
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001854:Bone Marrow Cells / Q000166:cytology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005337:Fibrin; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008297:Male; D009687:Nuclear Proteins; D017847:Patellar Ligament / Q000293:injuries* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D012097:Repressor Proteins; D017154:Stromal Cells / Q000166:cytology* / Q000637:transplantation; D023822:Tissue Engineering / Q000379:methods*; D014945:Wound Healing
chemical_list: D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C488451:ZNF253 protein, human; D005337:Fibrin; D003094:Collagen