title: Combination of ADMSCs and chondrocytes reduces hypertrophy and improves the functional properties of osteoarthritic cartilage.
abstract: OBJECTIVE
  To evaluate the therapeutic efficacy of Adipose derived MSCs (ADMSCs) in combination with chondrocytes in counteracting oxidative stress in chondrocytes in vitro and in rat model of osteoarthritis (OA).
  
  
  METHODS
  Cultured chondrocytes were exposed to oxidative stress with 200 μM Hydrogen peroxide (H2O2), followed by co-culture with ADMSCs or chondrocytes or combination of both cell types in a transwell culture system for 36 h. The cytoprotective effect was assessed by immunocytochemistry and gene expression analysis. In vivo study evaluated therapeutic effect of the above mentioned three treatments after transplantation in OA rats.
  
  
  RESULTS
  The Combination of ADMSCs + Chondrocytes decreased the extent of oxidative stress-induced damage of chondrocytes. Enhanced expression level of Acan and Collagen type-II alpha (Col2a1) with a correspondingly decreased expression of Collagen type-I alpha (Col1a1) and Matrix metallopeptidase 13 (Mmp13) was maximally observed in this group. Moreover, reduced count of annexin-V positive cells, Caspase (Casp3) gene expression and Lactate dehydrogenase (LDH) release with concomitantly enhanced viability and expression of proliferating cell nuclear antigen (PCNA) gene was observed. In vivo study showed that homing of cells and proteoglycan contents of knee joints were significantly better in ADMSCs + Chondrocytes transplanted rats. Increased expression of Acan and Col2a1 along with decreased expression of Col1a1 and Mmp13 indicated formation of hyaline cartilage in this group. These rats also demonstrated significantly reduced expression of Casp3 while increased expression of PCNA genes than the other cell transplanted groups.
  
  
  CONCLUSIONS
  Our results demonstrated that a combination of ADMSCs and chondrocytes may be a more effective therapeutic strategy against OA than the use of ADMSCs or chondrocytes separately.
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: M R
authors.initials: MR
authors.lastname: Ahmed
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: A
authors.initials: A
authors.lastname: Mehmood
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: F-ur-R
authors.initials: FU
authors.lastname: Bhatti
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
authors.forename: S N
authors.initials: SN
authors.lastname: Khan
authors.affiliation: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan; Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan. Electronic address: riazuddin@aimrc.org.
authors.forename: S
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000637:transplantation*; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007719:Knee Joint / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D016059:Range of Motion, Articular / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000627:therapeutic use*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D053509:Matrix Metalloproteinase 13; D012313:RNA; D014157:Transcription Factors; C117673:Msc protein, mouse; C507083:Mmp13 protein, rat
keywords: ADMSCs; Chondrocytes; Osteoarthritis; Oxidative stress