title: Effect of adipose-derived mesenchymal stromal cells on tendon healing in aging and estrogen deficiency: an in vitro co-culture model.
abstract: OBJECTIVE
  Aging and estrogen deficiency play a pivotal role in reducing tenocyte proliferation, collagen turnover and extracellular matrix remodeling. Mesenchymal stromal cells are being studied as an alternative for tendon regeneration, but little is known about the molecular events of adipose-derived mesenchymal stromal cells (ADSCs) on tenocytes in tendons compromised by aging and estrogen deficiency. The present in vitro study aims to compare the potential therapeutic effects of ADSCs, harvested from healthy young (sham) and aged estrogen-deficient (OVX) subjects, for tendon healing.
  
  
  METHODS
  An indirect co-culture system was set up with ADSCs, isolated from OVX or sham rats, and tenocytes from OVX rats. Cell proliferation, healing rate and gene expression were evaluated in both a standard culture condition and a microwound-healing model.
  
  
  RESULTS
  It was observed that tenocyte proliferation, healing rate and collagen expression improved after the addition of sham ADSCs in both culture situations. OVX ADSCs also increased tenocyte proliferation and healing rate but less compared with sham ADSCs. Decorin and Tenascin C expression increased in the presence of OVX ADSCs.
  
  
  CONCLUSIONS
  Findings suggest that ADSCs might be a promising treatment for tendon regeneration in advanced age and estrogen deficiency. However, some differences between allogenic and autologous cells were found and should be investigated in further in vivo studies. It appears that allogenic ADSCs improve tenocyte proliferation, collagen expression and the healing rate more than autologous cells. Autologous cells increase collagen expression only in the absence of an injury and increase Decorin and Tenascin C more than allogenic cells.
authors: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy. Electronic address: francesca.veronesi@ior.it.
authors: Francesca
authors: F
authors: Veronesi
authors: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors: Elena
authors: E
authors: Della Bella
authors: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy; Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Department Rizzoli RIT, Bologna, Italy.
authors: Paola
authors: P
authors: Torricelli
authors: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy; Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Department Rizzoli RIT, Bologna, Italy.
authors: Stefania
authors: S
authors: Pagani
authors: Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna, Italy; Laboratory of Biocompatibility, Innovative Technologies and Advanced Therapies, Department Rizzoli RIT, Bologna, Italy.
authors: Milena
authors: M
authors: Fini
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D018920:Coculture Techniques; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D058575:Decorin / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D010052:Ovariectomy; D017207:Rats, Sprague-Dawley; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D013710:Tendons / Q000166:cytology / Q000473:pathology*
chemical_list: C546880:Dcn protein, rat; D058575:Decorin; D004967:Estrogens; D019063:Tenascin; D003094:Collagen
keywords: adipose tissue; aging; estrogen deficiency; in vitro study; mesenchymal stromal cells; microwound; tendons