title: The effects of staged intra-articular injection of cultured autologous mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in caprine model.
abstract: BACKGROUND
  Treatment of chondral injuries remains a major issue despite the many advances made in cartilage repair techniques. Although it has been postulated that the use of marrow stimulation in combination with cell-based therapy may provide superior outcome, this has yet to be demonstrated. A pilot study was thus conducted to determine if bone marrow derived mesenchymal stromal cells (BM-MSCs) have modulatory effects on the repair outcomes of bone marrow stimulation (BMS) techniques.
  
  
  METHODS
  Two full-thickness chondral 5 mm diameter defects were created in tandem on the medial condyle of left stifle joints of 18 Boer caprine (N = 18). Goats were then divided equally into three groups. Simultaneously, bone marrow aspirates were taken from the iliac crests from the goats in Group 1 and were sent for BM-MSC isolation and expansion in vitro. Six weeks later, BMS surgery, which involves subchondral drilling at the defect sites, was performed. After two weeks, the knees in Group 1 were given autologous intra-articular BM-MSCs (N = 6). In Group 2, although BMS was performed there were no supplementations provided. In Group 3, no intervention was administered. The caprines were sacrificed after six months. Repairs were evaluated using macroscopic assessment through the International Cartilage Repair Society (ICRS) scoring, histologic grading by O'Driscoll score, biochemical assays for glycosaminoglycans (GAGs) and gene expressions for aggrecan, collagen II and Sox9.
  
  
  RESULTS
  Histological and immunohistochemical analyses demonstrated hyaline-like cartilage regeneration in the transplanted sites particularly in Group 1. In contrast, tissues in Groups 2 and 3 demonstrated mainly fibrocartilage. The highest ICRS and O'Driscoll scorings was also observed in Group 1, while the lowest score was seen in Group 3. Similarly, the total GAG/total protein as well as chondrogenic gene levels were expressed in the same order, that is highest in Group 1 while the lowest in Group three. Significant differences between these 3 groups were observed (P <0.05).
  
  
  CONCLUSIONS
  This study suggests that supplementing intra-articular injections of BM-MSCs following BMS knee surgery provides superior cartilage repair outcomes.
authors.forename: Hui Yin
authors.initials: HY
authors.lastname: Nam
authors.forename: Puvanan
authors.initials: P
authors.lastname: Karunanithi
authors.forename: Wagner Cheng
authors.initials: WC
authors.lastname: Loo
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Naveen
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Paisal
authors.initials: P
authors.lastname: Hussin
authors.forename: Lucy
authors.initials: L
authors.lastname: Chan
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
mesh_terms: D053674:Aggrecans / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002358:Cartilage, Articular / Q000293:injuries / Q000601:surgery*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D024043:Collagen Type II / Q000235:genetics; D015870:Gene Expression; D006025:Glycosaminoglycans / Q000378:metabolism; D006041:Goats; D007150:Immunohistochemistry; D007270:Injections, Intra-Articular; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D023421:Models, Animal; D010865:Pilot Projects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D053674:Aggrecans; D015703:Antigens, CD; D024043:Collagen Type II; D006025:Glycosaminoglycans; D055758:SOX9 Transcription Factor