Efficacy of intervertebral disc regeneration with stem cells - A systematic review and meta-analysis of animal controlled trials

Zhen Wang, Carmen M Terzic, Jay Smith, William D. Mauck, Randy A. Shelerud, Timothy Maus, Tai Hua Yang, Mohammad H Murad, Shanmiao Gou, Marisa J. Terry, Jason P. Dauffenbach, Mathew J. Pingree, Jason S. Eldrige, Khaled Mohammed, Khalid Benkhadra, Andre J van Wijnen, Wenchun Qu

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
JournalGene
DOIs
StateAccepted/In press - Feb 27 2015

Fingerprint

Intervertebral Disc
Meta-Analysis
Regeneration
Stem Cells
Confidence Intervals
Intervertebral Disc Degeneration
Stem Cell Transplantation
Clinical Trials
Collagen Type II
Messenger RNA

Keywords

  • Animal trial
  • Intervertebral disc
  • Regeneration
  • Stem cell therapy
  • Systematic review

ASJC Scopus subject areas

  • Genetics

Cite this

Efficacy of intervertebral disc regeneration with stem cells - A systematic review and meta-analysis of animal controlled trials. / Wang, Zhen; Terzic, Carmen M; Smith, Jay; Mauck, William D.; Shelerud, Randy A.; Maus, Timothy; Yang, Tai Hua; Murad, Mohammad H; Gou, Shanmiao; Terry, Marisa J.; Dauffenbach, Jason P.; Pingree, Mathew J.; Eldrige, Jason S.; Mohammed, Khaled; Benkhadra, Khalid; van Wijnen, Andre J; Qu, Wenchun.

In: Gene, 27.02.2015.

Research output: Contribution to journalArticle

Wang, Zhen ; Terzic, Carmen M ; Smith, Jay ; Mauck, William D. ; Shelerud, Randy A. ; Maus, Timothy ; Yang, Tai Hua ; Murad, Mohammad H ; Gou, Shanmiao ; Terry, Marisa J. ; Dauffenbach, Jason P. ; Pingree, Mathew J. ; Eldrige, Jason S. ; Mohammed, Khaled ; Benkhadra, Khalid ; van Wijnen, Andre J ; Qu, Wenchun. / Efficacy of intervertebral disc regeneration with stem cells - A systematic review and meta-analysis of animal controlled trials. In: Gene. 2015.
@article{ba1fcc79256244dc9ed13b30d285b898,
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.",
keywords = "Animal trial, Intervertebral disc, Regeneration, Stem cell therapy, Systematic review",
author = "Zhen Wang and Terzic, {Carmen M} and Jay Smith and Mauck, {William D.} and Shelerud, {Randy A.} and Timothy Maus and Yang, {Tai Hua} and Murad, {Mohammad H} and Shanmiao Gou and Terry, {Marisa J.} and Dauffenbach, {Jason P.} and Pingree, {Mathew J.} and Eldrige, {Jason S.} and Khaled Mohammed and Khalid Benkhadra and {van Wijnen}, {Andre J} and Wenchun Qu",
year = "2015",
month = "2",
day = "27",
doi = "10.1016/j.gene.2015.03.022",
language = "English (US)",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",

}

TY - JOUR

T1 - Efficacy of intervertebral disc regeneration with stem cells - A systematic review and meta-analysis of animal controlled trials

AU - Wang, Zhen

AU - Terzic, Carmen M

AU - Smith, Jay

AU - Mauck, William D.

AU - Shelerud, Randy A.

AU - Maus, Timothy

AU - Yang, Tai Hua

AU - Murad, Mohammad H

AU - Gou, Shanmiao

AU - Terry, Marisa J.

AU - Dauffenbach, Jason P.

AU - Pingree, Mathew J.

AU - Eldrige, Jason S.

AU - Mohammed, Khaled

AU - Benkhadra, Khalid

AU - van Wijnen, Andre J

AU - Qu, Wenchun

PY - 2015/2/27

Y1 - 2015/2/27

N2 - 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.

AB - 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.

KW - Animal trial

KW - Intervertebral disc

KW - Regeneration

KW - Stem cell therapy

KW - Systematic review

UR - http://www.scopus.com/inward/record.url?scp=84925359823&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925359823&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2015.03.022

DO - 10.1016/j.gene.2015.03.022

M3 - Article

C2 - 25796605

AN - SCOPUS:84928204482

JO - Gene

JF - Gene

SN - 0378-1119

ER -