title: The effects of microenvironment in mesenchymal stem cell-based regeneration of intervertebral disc.
abstract: BACKGROUND
  Recent studies have demonstrated new therapeutic strategy using transplantation of mesenchymal stem cells (MSCs), especially bone marrow-derived MSCs (BM-MSCs), to preserve intervertebral disc (IVD) structure and functions. It is important to understand whether and how the MSCs survive and thrive in the hostile microenvironment of the degenerated IVD. Therefore, this review majorly examines how resident disc cells, hypoxia, low nutrition, acidic pH, mechanical loading, endogenous proteinases, and cytokines regulate the behavior of the exogenous MSCs.
  
  
  OBJECTIVE
  To review and summarize the effect of the microenvironment in biological characteristics of BM-MSCs for IVD regeneration; the presence of endogenous stem cells and the state of the art in the use of BM-MSCs to regenerate the IVD in vivo were also discussed.
  
  
  METHODS
  Literature review.
  
  
  METHODS
  MEDLINE electronic database was used to search for articles concerning stem/progenitor cell isolation from the IVD, regulation of the components of microenvironment for MSCs, and MSC-based therapy for IVD degeneration. The search was limited to English language.
  
  
  RESULTS
  Stem cells are probably resident in the disc, but exogenous stem cells, especially BM-MSCs, are currently the most popular graft cells for IVD regeneration. The endogenous disc cells and the biochemical and biophysical components in the degenerating disc present a complicated microenvironment to regulate the transplanted BM-MSCs. Although MSCs regenerate the mildly degenerative disc effectively in the experimental and clinical trials, many underlying questions are in need of further investigation.
  
  
  CONCLUSIONS
  There has been a dramatic improvement in the understanding of potential MSC-based therapy for IVD regeneration. The use of MSCs for IVD degeneration is still at the stage of preclinical and Phase 1 studies. The effects of the disc microenvironment in MSCs survival and function should be closely studied for transferring MSC transplantation from bench to bedside successfully.
authors: Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 5/F Professor Block, Pokfulam, Hong Kong, China.
authors: Yong-Can
authors: YC
authors: Huang
authors: Victor Y L
authors: VY
authors: Leung
authors: William W
authors: WW
authors: Lu
authors: Keith D K
authors: KD
authors: Luk
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology*; D055959:Intervertebral Disc Degeneration / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D012038:Regeneration / Q000502:physiology*; D055153:Stem Cell Niche / Q000502:physiology*