title: Efficacy of intervertebral disc regeneration with stem cells - a systematic review and meta-analysis of animal controlled trials.
abstract: Management of intervertebral disc (IVD) degenerative disease is challenging, as it is accompanied by irreversible loss of IVD cells. Stem cell transplantation to the disc has shown promise in decelerating or arresting the degenerative process. Multiple pre-clinical animal trials have been conducted, but with conflicting outcomes. To assess the effect of stem cell transplantation, a systematic review and meta-analysis was performed. A comprehensive literature search was conducted through Week 3, 2015. Inclusion criteria consisted of controlled animal trials. Two reviewers screened abstracts and full texts. Disagreements were resolved by a third reviewer. Random effects models were constructed to pool standardized mean difference (SMD). Twenty two studies were included; nine of which were randomized. Statistically significant differences were found with the stem cell group exhibiting increased disc height index (SMD=3.64, 95% confidence interval (CI): 2.49, 4.78; p<0.001), increased MRI T2 signal intensity (SMD=2.28, 95% CI: 1.48, 3.08; p<0.001), increased Type II collagen mRNA expression (SMD=3.68, 95% CI: 1.66, 5.70; p<0.001), and decreased histologic disc degeneration grade (SMD=-2.97, 95% CI: -3.97, -1.97; p<0.001). There was statistical heterogeneity between studies that could not be explained with pre-planned subgroup analyses based on animal species, study designs, and transplanted cell types. Stem cells transplanted to the IVD in quadruped animals decelerate or arrest the IVD degenerative process. Further studies in human clinical trials will be needed to understand if such benefit can be translated to bipedal humans.
authors: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA.
authors: Zhen
authors: Z
authors: Wang
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, MN 55905, USA.
authors: Carman M
authors: CM
authors: Perez-Terzic
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
authors: Jay
authors: J
authors: Smith
authors: Department of Anesthesiology Pain Division, Mayo Clinic, Rochester, MN 55905, USA.
authors: William D
authors: WD
authors: Mauck
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Spine Center, Mayo Clinic, Rochester, MN 55905, USA.
authors: Randy A
authors: RA
authors: Shelerud
authors: Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA.
authors: Timothy P
authors: TP
authors: Maus
authors: Department of Biomedical Engineering, National Cheng Kung University, Taiwan; Biomechanics Laboratory and Tendon and Soft Tissue Biology Laboratory, Division of Orthopedic Research, Mayo Clinic, Rochester, MN 55905, USA.
authors: Tai-Hua
authors: TH
authors: Yang
authors: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA.
authors: Mohammad Hassan
authors: MH
authors: Murad
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Department of Anesthesiology Pain Division, Mayo Clinic, Rochester, MN 55905, USA.
authors: Shanmiao
authors: S
authors: Gou
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
authors: Marisa J
authors: MJ
authors: Terry
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
authors: Jason P
authors: JP
authors: Dauffenbach
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Department of Anesthesiology Pain Division, Mayo Clinic, Rochester, MN 55905, USA.
authors: Mathew J
authors: MJ
authors: Pingree
authors: Department of Anesthesiology Pain Division, Mayo Clinic, Rochester, MN 55905, USA.
authors: Jason S
authors: JS
authors: Eldrige
authors: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA.
authors: Khaled
authors: K
authors: Mohammed
authors: Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA.
authors: Khalid
authors: K
authors: Benkhadra
authors: Department of Orthopedics, Rochester, MN 55905, USA.
authors: Andre J
authors: AJ
authors: van Wijnen
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA; Department of Anesthesiology Pain Division, Mayo Clinic, Rochester, MN 55905, USA; Spine Center, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: qu.wenchun@mayo.edu.
authors: Wenchun
authors: W
authors: Qu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007403:Intervertebral Disc / Q000503:physiopathology*; D055959:Intervertebral Disc Degeneration / Q000628:therapy*; D012038:Regeneration; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
keywords: Animal trial; Intervertebral disc; Regeneration; Stem cell therapy; Systematic review