title: Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen.
abstract: OBJECTIVE
  Meniscal regeneration was previously shown to be enhanced by injection of mesenchymal stem/stromal cells (MSCs) but the mode of action of the MSCs was not established. The aim of this study was to define how injection of MSCs enhances meniscal regeneration.
  
  
  METHODS
  A hemi-meniscectomy model in rats was used. Rat-MSCs (rMSCs) or human-MSCs (hMSCs) were injected into the right knee joint after the surgery, and PBS was injected into the left. The groups were compared macroscopically and histologically at 2, 4, and 8 weeks. The changes in transcription in both human and rat genes were assayed by species-specific microarrays and real-time RT-PCRs.
  
  
  RESULTS
  Although the number of hMSCs decreased with time, hMSCs enhanced meniscal regeneration in a manner similar to rMSCs. hMSCs injection increased expression of rat type II collagen (rat-Col II), and inhibited osteoarthritis progression. The small fraction of hMSCs was activated to express high levels of a series of genes including Indian hedgehog (Ihh), parathyroid hormone-like hormone (PTHLH), and bone morphogenetic protein 2 (BMP2). The presence of hMSCs triggered the subsequent expression of rat-Col II. An antagonist of hedgehog signaling inhibited the expression of rat-Col II and an agonist increased expression of rat-Col II in the absence of hMSCs.
  
  
  CONCLUSIONS
  Despite rapid reduction in cell numbers, intra-articular injected hMSCs were activated to express Ihh, PTHLH, and BMP2 and contributed to meniscal regeneration. The hedgehog signaling was essential in enhancing the expression of rat-Col II, but several other factors provided by the hMSCs probably contributed to the repair.
authors: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, TX 76502, USA.
authors: M
authors: M
authors: Horie
authors: H
authors: H
authors: Choi
authors: R H
authors: RH
authors: Lee
authors: R L
authors: RL
authors: Reger
authors: J
authors: J
authors: Ylostalo
authors: T
authors: T
authors: Muneta
authors: I
authors: I
authors: Sekiya
authors: D J
authors: DJ
authors: Prockop
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D017690:Cell Transplantation; D024043:Collagen Type II / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008592:Menisci, Tibial / Q000378:metabolism / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000502:physiology*
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D024043:Collagen Type II; D053823:Hedgehog Proteins; C550919:Ihh protein, rat