title: Tenogenesis of bone marrow-, adipose-, and tendon-derived stem cells in a dynamic bioreactor.
abstract: Tendons are frequently damaged and fail to regenerate, leading to pain, loss of function, and reduced quality of life. Mesenchymal stem cells (MSCs) possess clinically useful tissue-regenerative properties and have been exploited for use in tendon tissue engineering and cell therapy. However, MSCs exhibit phenotypic heterogeneity based on the donor tissue used, and the efficacy of cell-based treatment modalities may be improved by optimizing cell source based on relative differentiation capacity. Equine MSCs were isolated from bone marrow (BM), adipose (AD), and tendon (TN), expanded in monolayer prior to seeding on decellularized tendon scaffolds (DTS), and cell-laden constructs were placed in a bioreactor designed to mimic the biophysical environment of the tendon. It was hypothesized that TN MSCs would differentiate toward a tendon cell phenotype better than BM and AD MSCs in response to a conditioning period involving cyclic mechanical stimulation for 1 hour per day at 3% strain and 0.33 Hz. All cell types integrated into DTS adopted an elongated morphology similar to tenocytes, expressed tendon marker genes, and improved tissue mechanical properties after 11 days. TN MSCs expressed the greatest levels of scleraxis, collagen type-I, and cartilage oligomeric matrix protein. Major histocompatibility class-II protein mRNA expression was not detected in any of the MSC types, suggesting low immunogenicity for allogeneic transplantation. The results suggest that TN MSCs are the ideal cell type for regenerative medicine therapies for tendinopathies, exhibiting the most mature tendon-like phenotype in vitro. When TN MSCs are unavailable, BM or AD MSCs may serve as robust alternatives.
authors.affiliation: a Program in Biomedical and Veterinary Sciences, Marion duPont Scott Equine Medical Center , Virginia Tech , Leesburg , VA , USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Youngstrom
authors.affiliation: a Program in Biomedical and Veterinary Sciences, Marion duPont Scott Equine Medical Center , Virginia Tech , Leesburg , VA , USA.
authors.forename: Jade E
authors.initials: JE
authors.lastname: LaDow
authors.affiliation: b Department of Large Animal Clinical Sciences, Marion duPont Scott Equine Medical Center , Virginia Tech , Leesburg , VA , USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Barrett
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001696:Biomechanical Phenomena; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000166:cytology*; D002417:Cattle; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D003114:Colony-Forming Units Assay; D005109:Extracellular Matrix / Q000378:metabolism; D020869:Gene Expression Profiling; D006025:Glycosaminoglycans / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006736:Horses; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D038081:Organogenesis; D013710:Tendons / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D006025:Glycosaminoglycans; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D003094:Collagen
keywords: Bioreactor; differentiation; mesenchymal stem cells; regenerative medicine; tendon