Effect of Stem Cell Therapy on Bone Mineral Density: A Meta-Analysis of Preclinical Studies in Animal Models of Osteoporosis

Feng Li, Changlin Zhou, Liang Xu, Shuqing Tao, Jingyi Zhao, Qun Gu, Feng Li, Changlin Zhou, Liang Xu, Shuqing Tao, Jingyi Zhao, Qun Gu

Abstract

Background: Preclinical studies of the therapeutic role of stem cell based therapy in animal models of osteoporosis have largely yielded inconsistent results. We performed a meta-analysis to provide an overview of the currently available evidence.

Methods: Pubmed, Embase and Cochrane Library databases were systematically searched for relevant controlled studies. A random-effect model was used for pooled analysis of the effect of stem cell based therapy on bone mineral density (BMD). Stratified analyses were performed to explore the effect of study characteristics on the outcomes.

Results: Pooled results from 12 preclinical studies (110 animals in stem cell treatment groups, and 106 animals in control groups) indicated that stem cell based treatment was associated with significantly improved BMD (standardized mean difference [SMD] = 1.29, 95% Confidence Interval [CI]: 0.84-1.74, P < 0.001) with moderate heterogeneity (Cochrane's Q test: P = 0.02, I2 = 45%) among the constituent studies. Implantation of bone marrow cells, bone marrow mesenchymal stem cells, adipose-derived stem cells, and human umbilical cord blood-derived CD34+ cells, were all associated with improved BMD as compared to that in the controls (P < 0.05 for all); the only exception being the use of embryonic stem cell transplantation (P > 0.05). Egger's test detected potential publication bias (P = 0.055); however, 'trim and fill' analysis yielded similar results after statistically incorporating the hypothetical studies in the analysis (SMD = 1.24, 95% CI: 0.32-2.16, P < 0.001).

Conclusions: Stem cell transplantation may improve BMD in animal models of osteoporosis. Our meta-analysis indicates a potential therapeutic role of stem cell based therapy for osteoporosis, and serves to augment the rationale for clinical studies.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow diagram illustrating the study…
Fig 1. Flow diagram illustrating the study selection criteria for the meta-analysis.
BMD, Bone mineral density
Fig 2. Forest plot of the meta-analysis…
Fig 2. Forest plot of the meta-analysis of standardized mean difference of bone mineral density by study group (stem cell based treatment- vs. control group).
BMD, Bone mineral density; SD, standard deviation; CI, confidence interval; df, degrees of freedom
Fig 3. Funnel plot using ‘trim and…
Fig 3. Funnel plot using ‘trim and fill’ method for meta-analysis of standardized mean difference (SMD) of bone mineral density for animals assigned to the stem cell based treatment and the control groups.
The unfilled data points represent the identified studies included in the meta-analysis, and the black dots represent the imputed missing studies after adjustment for publication bias. s.e. of SMD; standard error of the standardized mean difference

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Source: PubMed

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