title: Tissue engineering of tendons and ligaments by human bone marrow stromal cells in a liquid fibrin matrix in immunodeficient rats: results of a histologic study.
abstract: BACKGROUND
  The original complex structure and mechanical properties are not fully restored after ligament and tendon injuries. Due to their high proliferation rate and differentiation potential, Bone Marrow Stromal Cells (BMSC) are considered to be an ideal cell source for tissue engineering to optimize the healing process. Ideal matrices for tissue engineering of ligaments and tendons should allow for homogenous cell seeding and offer sufficient stability.
  
  
  METHODS
  A mixture of human BMSC and liquid fibrin glue was injected into a standardized full-thickness window defect of the patellar tendon of immunodeficient rats (BMSC group). The histology of the tissue was analysed 10 and 20 days postoperatively and compared to four control groups. These groups consisted of a cohort with a mixture of human fibroblasts and fibrin glue, fibrin glue without cells, a defect group without treatment, and a group with uninjured patellar tendon tissue.
  
  
  RESULTS
  Tendon defects in the BMSC group revealed dense collagen fibres and spindle-shaped cells, which were mainly orientated along the loading axis. Histologic sections of the control groups, especially of untreated defects and of defects filled with fibrin glue only, showed irregular patterns of cell distribution, irregular formed cell nucleoli and less tissue maturation. Compared to healthy tendon tissue, higher numbers of cells and less intense matrix staining was observed in the BMSC group. No ectopic bone or cartilage formation was observed in any specimen.
  
  
  CONCLUSIONS
  Injection of human BMSC in a fibrin glue matrix appears to lead to more mature tissue formation with more regular patterns of cell distribution. Advantages of this "in-vivo" tissue engineering approach are a homogenous cell-matrix mixture in a well-known and approved biological matrix, and simple, minimally-invasive application by injection.
authors.affiliation: Trauma Department, Hanover Medical School (MHH), Carl-Neuberg-Str 1, 30625, Hanover, Germany. hankemeier.stefan@mh-hannover.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Hankemeier
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
authors.forename: Marco
authors.initials: M
authors.lastname: Ezechieli
authors.forename: Tanja
authors.initials: T
authors.lastname: Barkhausen
authors.forename: Matthew
authors.initials: M
authors.lastname: Austin
authors.forename: Michael
authors.initials: M
authors.lastname: Jagodzinski
authors.forename: Rupert
authors.initials: R
authors.lastname: Meller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bosch
authors.forename: Christian
authors.initials: C
authors.lastname: Krettek
authors.forename: Johannes
authors.initials: J
authors.lastname: Zeichen
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D008022:Ligaments / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects; D013710:Tendons / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D015718:Fibrin Tissue Adhesive