title: A nondenatured, noncrosslinked collagen matrix to deliver stem cells to the heart.
abstract: OBJECTIVE
  Stem cell transplantation holds promise as a therapeutic approach for the repair of damaged myocardial tissue. One challenge of this approach is efficient delivery and long-term retention of the stem cells. Although several synthetic and natural biomaterials have been developed for this purpose, the ideal formulation has yet to be identified.
  
  
  METHODS
  Here we investigate the utility of a nondenatured, noncrosslinked, commercially available natural biomaterial (TissueMend(®) [TEI Biosciences, Boston, MA, USA]) for delivery of human mesenchymal stem cells (MSCs) to the murine heart.
  
  
  RESULTS
  We found that MSCs attached, proliferated and migrated within and out of the TissueMend matrix in vitro. Human MSCs delivered to damaged murine myocardium via the matrix (2.3 × 10(4) ± 0.8 × 10(4) CD73(+) cells/matrix) were maintained in vivo for 3 weeks and underwent at least three population doublings during that period (21.9 × 10(4) ± 14.4 × 10(4) CD73(+) cells/matrix). In addition, collagen within the TissueMend matrix could be remodeled by MSCs in vivo, resulting in a significant decrease in the coefficient of alignment of fibers (0.12 ± 0.12) compared with the matrix alone (0.28 ± 0.07), and the MSCs were capable of migrating out of the matrix and into the host tissue.
  
  
  CONCLUSIONS
  Thus, TissueMend matrix offers a commercially available, biocompatible and malleable vehicle for the delivery and retention of stem cells to the heart.
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kouris
authors.forename: Jayne M
authors.initials: JM
authors.lastname: Squirrell
authors.forename: Jangwook P
authors.initials: JP
authors.lastname: Jung
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Pehlke
authors.forename: Timothy
authors.initials: T
authors.lastname: Hacker
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Eliceiri
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Ogle
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000627:therapeutic use*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy; D009206:Myocardium / Q000166:cytology*; D012038:Regeneration
chemical_list: D001672:Biocompatible Materials; D003094:Collagen