title: Potential use of human adipose mesenchymal stromal cells for intervertebral disc regeneration: a preliminary study on biglycan-deficient murine model of chronic disc degeneration.
abstract: BACKGROUND
  Biglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn-/0) mice lack this protein and undergo spontaneous IVD degeneration with aging, thus representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. The purpose of the present study was to assess the possible beneficial effects of adipose-derived stromal cells (ADSCs) implants in the Bgn-/0 mouse model.
  
  
  METHODS
  To evaluate ADSC implant efficacy, Bgn-/0 mice were intradiscally (L1-L2) injected with 8x104 ADSCs at 16 months old, when mice exhibit severe and complete IVD degeneration, evident on both 7Tesla Magnetic Resonance Imaging (7TMRI) and histology. Placebo and ADSCs treated Bgn-/0 mice were assessed by 7TMRI analysis up to 12 weeks post-transplantation. Mice were then sacrificed and implanted discs were analyzed by histology and immunohistochemistry for the presence of human cells and for the expression of biglycan and aggrecan in the IVD area.
  
  
  RESULTS
  After in vivo treatment, 7TMRI revealed evident increase in signal intensity within the discs of mice that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated that human ADSC survival occurred in the injected discs up to 12 weeks after implant. These cells acquired a positive expression for biglycan, and this proteoglycan was specifically localized in human cells. Moreover, ADSC treatment resulted in a significant increase of aggrecan tissue levels.
  
  
  CONCLUSIONS
  Overall, this work demonstrates that ADSC implant into degenerated disc of Bgn-/0 mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan. This suggests a potential benefit of ADSC implant in the treatment of chronic degenerative disc disease and prompts further studies in this field.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marfia
authors.forename: Rolando
authors.initials: R
authors.lastname: Campanella
authors.forename: Stefania Elena
authors.initials: SE
authors.lastname: Navone
authors.forename: Ileana
authors.initials: I
authors.lastname: Zucca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scotti
authors.forename: Matteo
authors.initials: M
authors.lastname: Figini
authors.forename: Clara
authors.initials: C
authors.lastname: Di Vito
authors.forename: Giulio
authors.initials: G
authors.lastname: Alessandri
authors.forename: Laura
authors.initials: L
authors.lastname: Riboni
authors.forename: Eugenio
authors.initials: E
authors.lastname: Parati
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D053674:Aggrecans / Q000096:biosynthesis; D000818:Animals; D058578:Biglycan / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000000981:diagnostic imaging / Q000503:physiopathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011859:Radiography; D012038:Regeneration; D014183:Transplantation, Heterologous
chemical_list: D053674:Aggrecans; D058578:Biglycan