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Stem Cell Research & Therapy Mar 2015The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data from animal studies can be used to inform clinical trial design. To conduct a systematic review and meta-analysis to (i) systematically review the literatures describing the effect of MSCs therapy in animal models of TBI, (ii) determine the estimated effect size of functional locomotor recovery after experimental TBI, and (iii) to provide empirical evidence of biological factors associated with greater efficacy.
METHODS
We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the efficacy of MSCs in animal models of TBI. Two investigators independently assessed the identified studies. We extracted the details of individual study characteristics from each publication, assessed study quality, evaluated the effect sizes of MSCs treatment, and performed stratified meta-analysis and meta-regression, to assess the influence of study design on the estimated effect size. The presence of small effect sizes was investigated using funnel plots and Egger's tests.
RESULTS
Twenty-eight eligible controlled studies were identified. The study quality was modest. Between-study heterogeneity was large. Meta-analysis showed that MSCs exert statistically significant positive effects on sensorimotor and neurological motor function. For sensorimotor function, maximum effect size in studies with a quality score of 5 was found in the weight-drop impact injury TBI model established in male SD rats, to which syngeneic umbilical cord-derived MSCs intracerebrally at cell dose of (1-5)×10(6) was administered r 6 hours following TBI, using ketamine as anesthetic agent. For neurological motor function, effect size was maximum for studies with a quality score of 5, in which the weight-drop impact injury TBI models of the female Wistar rats were adopted, with administration syngeneic bone marrow-derived MSCs intravenously at cell dose of 5×10(6) at 2 months after TBI, using sevofluorane as anesthetic agent.
CONCLUSIONS
We conclude that MSCs therapy may improve locomotor recovery after TBI. However, additional well-designed and well-reported animal studies are needed to guide further clinical studies.
Topics: Animals; Brain Injuries; Cell- and Tissue-Based Therapy; Disease Models, Animal; Female; Locomotion; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Motor Activity; Rats; Rats, Sprague-Dawley; Rats, Wistar; Recovery of Function
PubMed: 25881229
DOI: 10.1186/s13287-015-0034-0 -
Thrombosis Research Mar 2020Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the... (Review)
Review
BACKGROUND
Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the anticoagulant effects, potential anti-tumor effects of DOACs have also been studied in animal cancer models. In this study, we summarize the effects of DOACs on cancer growth and metastasis in animal models through a systematic review with a qualitative analysis.
METHODS
PubMed, EMBASE and Web of Science were systematically searched for original studies that describe animal models of cancer in which one of the experimental groups received DOAC monotherapy, and which reported quantitatively on primary tumor or metastases.
RESULTS
Nine studies - reporting a total of 19 animal experiments - met the inclusion criteria. These 19 experiments included spontaneous cancer (n = 2), carcinogenicity (n = 2), xenograft (n = 7) and syngeneic (n = 8) models, encompassing orthotopic (n = 7), subcutaneous (n = 5), intraperitoneal (n = 1) and intravenous (n = 2) injection of cancer cells and included treatments with the DOACs ximelagatran (n = 4), dabigatran etexilate (n = 6) and/or rivaroxaban (n = 11). DOAC treatment decreased tumor growth at implanted and metastatic site in 18.8% (3/16) and 20.0% (3/15) of the experiments, respectively. Conversely, DOACs increased tumor growth at implanted and metastatic site in 6.3% (1/16) and 20.0% (3/15) of the experiments, respectively.
CONCLUSION
DOAC monotherapy resulted in neoplastic changes in a rat carcinogenicity study, showed a lack of effect in mouse xenograft models, while the effect on cancer growth and metastasis in mouse syngeneic models depended on the timing of DOAC treatment and type of cancer model used.
Topics: Administration, Oral; Animals; Anticoagulants; Antithrombins; Dabigatran; Humans; Mice; Models, Animal; Neoplasms; Pyrazoles; Pyridones; Rats; Rivaroxaban; Venous Thromboembolism
PubMed: 31945588
DOI: 10.1016/j.thromres.2019.12.022 -
NPJ Regenerative Medicine Oct 2021Mesenchymal stromal cells (MSCs) are widely used in preclinical models of traumatic brain injury (TBI). Results are promising in terms of neurological improvement but...
Mesenchymal stromal cells (MSCs) are widely used in preclinical models of traumatic brain injury (TBI). Results are promising in terms of neurological improvement but are hampered by wide variability in treatment responses. We made a systematic review and meta-analysis: (1) to assess the quality of evidence for MSC treatment in TBI rodent models; (2) to determine the effect size of MSCs on sensorimotor function, cognitive function, and anatomical damage; (3) to identify MSC-related and protocol-related variables associated with greater efficacy; (4) to understand whether MSC manipulations boost therapeutic efficacy. The meta-analysis included 80 studies. After TBI, MSCs improved sensorimotor and cognitive deficits and reduced anatomical damage. Stratified meta-analysis on sensorimotor outcome showed similar efficacy for different MSC sources and for syngeneic or xenogenic transplants. Efficacy was greater when MSCs were delivered in the first-week post-injury, and when implanted directly into the lesion cavity. The greatest effect size was for cells embedded in matrices or for MSC-derivatives. MSC therapy is effective in preclinical TBI models, improving sensorimotor, cognitive, and anatomical outcomes, with large effect sizes. These findings support clinical studies in TBI.
PubMed: 34716332
DOI: 10.1038/s41536-021-00182-8 -
Advances in Experimental Medicine and... 2018The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect....
The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect. We have assessed factors responsible for the contrasting effects of MSCs on tumour growth by doing a meta-analysis of existing literature between 2000 and May 2017. We assessed 183 original research articles comprising 338 experiments. We considered (a) in vivo and in vitro experiments, (b) whether in vivo studies were syngeneic or xenogeneic, and (c) if animals were immune competent or deficient. Furthermore, the sources and types of cancer cells and MSCs were considered together with modes of cancer induction and MSC administration. 56% of all 338 experiments reported that MSCs promote tumour growth. 78% and 79% of all experiments sourced human MSCs and cancer cells, respectively. MSCs were used in their naïve and engineered form in 86% and 14% of experiments, respectively, the latter to produce factors that could alter either their activity or that of the tumour. 53% of all experiments were conducted in vitro with 60% exposing cancer cells to MSCs via coculture. Of all in vivo experiments, 79% were xenogeneic and 63% were conducted in immune-competent animals. Tumour growth was inhibited in 80% of experiments that used umbilical cord-derived MSCs, whereas tumour growth was promoted in 64% and 57% of experiments that used bone marrow- and adipose tissue-derived MSCs, respectively. This contrasting effect of MSCs on tumour growth observed under different experimental conditions may reflect differences in experimental design. This analysis calls for careful consideration of experimental design given the large number of MSC clinical trials currently underway.
Topics: Adipose Tissue; Animals; Bone Marrow Cells; Cell Proliferation; Humans; Mesenchymal Stem Cells; Neoplasms; Research Design
PubMed: 29139088
DOI: 10.1007/5584_2017_118 -
Current Reviews in Clinical and... Apr 2024The use of appropriate animal models for cancer studies is a major challenge, particularly for investigators who lack the resources to maintain and use xenograft animals...
Cell-Derived Allograft Models as a Solution to the Obstacles of Preclinical Studies under Limited Resources: A Systematic Review on Experimental Lung Cancer Animal Models.
BACKGROUND
The use of appropriate animal models for cancer studies is a major challenge, particularly for investigators who lack the resources to maintain and use xenograft animals or genetically engineered mouse models (GEMM). In addition, several countries intending to incorporate these models must conduct importation procedures, posing an additional challenge.
OBJECTIVE
This review aimed to explore the use of cell-derived allograft or syngeneic models under limited resources. The results can be used by investigators, specifically from low-middle-income countries, to contribute to lung cancer eradication.
METHOD
A literature search was carried out on various databases, including PubMed, Web of Science, and Scopus. In addition, the publication year of the selected articles was set between 2013 and 2023 with different search components (SC), namely lung cancer (SC1), animal models (SC2), and preclinical studies (SC3).
RESULTS
This systematic review focused on selecting animals, cells, and methods that could be applied to generating allograft-type lung cancer animal models from 101 included articles.
CONCLUSION
Based on the results, the use of cell-derived allograft models in cancer studies is feasible and relevant, and it provides valuable insights regarding the conditions with limited resources.
PubMed: 38659262
DOI: 10.2174/0127724328295592240419064719