scholarly journals Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

2018 ◽  
Vol 29 (3) ◽  
pp. 321-332 ◽  
Author(s):  
Suleiman Alhaji Muhammad ◽  
Norshariza Nordin ◽  
Sharida Fakurazi
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Conditioned Medium ◽  
Tissue Regeneration ◽  
Therapeutic Benefit ◽  
Risk Of Bias ◽  
Preclinical Studies

AbstractInjury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium inin vivoanimal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

scholarly journals Stem Cells as Therapy for Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis of Preclinical Studies

2020 ◽  
Vol 8 ◽  
Author(s):  
Eduardo Villamor-Martinez ◽  
Tamara Hundscheid ◽  
Boris W. Kramer ◽  
Carlijn R Hooijmans ◽  
Eduardo Villamor
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Cell Therapy ◽  
Necrotizing Enterocolitis ◽  
Stem Cell Therapy ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Intestinal Injury

Background: Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal condition among very and extremely preterm infants. Stem cell therapy has shown some promising protective effects in animal models of intestinal injury, including NEC, but no systematic review has yet evaluated the preclinical evidence of stem cell therapy for NEC prevention or treatment.Methods: PubMed and EMBASE databases were searched for studies using an animal model of NEC with stem cells or their products. The SYRCLE tool was used for the assessment of risk of bias. A random-effects model was used to pool odds ratios (ORs) and 95% confidence interval (CI).Results: We screened 953 studies, of which nine (eight rat and one mouse models) met the inclusion criteria. All animal models induced NEC by a combination of hypothermia, hypoxia, and formula feeding. Risk of bias was evaluated as unclear on most items for all studies included. Meta-analysis found that both mesenchymal and neural stem cells and stem cell-derived exosomes reduced the incidence of all NEC (OR 0.22, 95% CI 0.16–0.32, k = 16), grade 2 NEC (OR 0.41, 95% CI 0.24–0.70, k = 16), and grade 3–4 NEC (OR 0.28, 95% CI 0.19–0.42, k = 16). k represents the number of independent effect sizes included in each meta-analysis. The effect of the exosomes was similar to that of the stem cells. Stem cells and exosomes also improved 4-day survival (OR 2.89 95% CI 2.07–4.04, k = 9) and 7-day survival (OR 3.96 95% CI 2.39–6.55, k = 5) after experimental NEC. Meta-analysis also found that stem cells reduced other indicators of intestinal injury.Conclusion: The data from this meta-analysis suggest that both stem cells and stem cell-derived exosomes prevented NEC in rodent experimental models. However, unclear risk of bias and incomplete reporting underline that poor reporting standards are common and hamper the reliable interpretation of preclinical evidence for stem cell therapy for NEC.

The Effect of Plantago major on Wound Healing in Preclinical Studies: A Systematic Review

2021 ◽  
Vol 67 (1) ◽  
pp. 27-34
Author(s):  
Fernanda Cardoso ◽  
Jéssica Breder ◽  
Priscila Apolinário ◽  
Henrique Oliveia ◽  
Maria Saidel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Preclinical Studies ◽  
Plantago Major ◽  
Best Response ◽  
Meta Analyses

BACKGROUND: Plantago major is a medicinal plant that has been used for centuries to treat various health conditions including wounds. PURPOSE: To investigate the effectiveness of the topical use of P major in healing skin wounds in animal models. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted. Seven (7) electronic databases (Virtual Health Library, Public/Publisher MEDLINE, Scopus, Web of Science, Embase, Cumulative Index of Nursing and Allied Health Literature, and CAB Direct) were searched for controlled studies published in English from January 2006 to March 2020. The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies tools guided the evaluation of the studies and determined their quality. The Systematic Review Center for Laboratory Animal Experimentation was used to assess the risk of bias. RESULTS: Of the 176 publications identified, 4 met the inclusion criteria. Studies included 20 to 100 animals and varying concentrations of P major. There were no reports of losses during research. Wound healing was assessed between 17 and 21 days following wounding. The best response in terms of wound contraction rate occurred with 10%, 20%, and 50% concentrations when compared with control groups. One (1) study did not have an animal ethics committee review. All studies had a high risk of bias and a lack of methodological rigor. CONCLUSION: The results of this review did not find evidence about the in vivo effectiveness of P major for wound healing. More rigorous preclinical studies with adequate sample sizes are required to identify the best concentrations and formulations as well as increase understanding about the mechanisms of action of P major in wound healing.

scholarly journals Efficacy of mesenchymal stromal cells in preclinical models of necrotizing enterocolitis: a systematic review protocol

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1011
Author(s):  
Camille Maltais-Bilodeau ◽  
Ewa Henckel ◽  
Kelly D. Cobey ◽  
Nadera Ahmadzai ◽  
Becky Skidmore ◽  
...  
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Necrotizing Enterocolitis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bowel Perforation ◽  
Risk Of Bias ◽  
Sufficient Evidence ◽  
Preclinical Models

Introduction: Necrotizing enterocolitis is an acute inflammatory disease of the intestine that can lead to necrosis and bowel perforation. It is a severe complication of preterm birth. It’s mortality rate is up to 50% and survival after necrotizing enterocolitis leads to long-term complications. The current treatment is supportive and includes bowel rest and decompression and antibiotics. Thus, new treatments are necessary to reduce mortality and morbidity. Mesenchymal stromal cells are known to have anti-inflammatory properties and might be a promising option for treatment. Here we present a protocol for a systematic review with the aim to explore the efficacy of cell therapies with mesenchymal stromal cells in animal models of necrotizing enterocolitis. The primary outcome is histological signs of necrotizing enterocolitis. Additional outcomes include survival, bowel perforation, gut permeability, gut motility, levels of inflammatory markers, cytokine levels and adverse events. Methods: We will conduct a systematic search of MEDLINE, Embase, and Web of Science databases. The retrieved records will be screened individually by two investigators. We will include all preclinical in vivo animal models of experimentally induced necrotizing enterocolitis that evaluate the efficacy of mesenchymal stromal cells or other cell therapy treatments. Outcome data will be extracted from each article and risk of bias assessment performed. Funnel plots and SYRCLE’s risk of bias tool for animal studies will be used. Data will be reported as ratios, divided in predefined subgroups where relevant. Conclusions: This systematic review aims to examine the efficacy of mesenchymal stromal cells in preclinical models of necrotizing enterocolitis and whether there is sufficient evidence to support a clinical trial of efficacy and safety of the treatment with mesenchymal stromal cells in infants with necrotizing enterocolitis.

scholarly journals Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to GAlert

2018 ◽  
Vol 115 (19) ◽  
pp. E4463-E4472 ◽  
Author(s):  
Geoffrey Lee ◽  
Ana Isabel Espirito Santo ◽  
Stefan Zwingenberger ◽  
Lawrence Cai ◽  
Thomas Vogl ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Cell Function ◽  
Elective Surgery ◽  
High Mobility ◽  
Underlying Mechanism ◽  
Clinical Scenarios ◽  
Stem And Progenitor Cells

A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells. However, ways of enhancing endogenous stem cell function remain poorly defined. Injury leads to the release of danger signals which are known to modulate the immune response, but their role in stem cell-mediated repair in vivo remains to be clarified. Here we show that high mobility group box 1 (HMGB1) is released following fracture in both humans and mice, forms a heterocomplex with CXCL12, and acts via CXCR4 to accelerate skeletal, hematopoietic, and muscle regeneration in vivo. Pretreatment with HMGB1 2 wk before injury also accelerated tissue regeneration, indicating an acquired proregenerative signature. HMGB1 led to sustained increase in cell cycling in vivo, and using Hmgb1−/− mice we identified the underlying mechanism as the transition of multiple quiescent stem cells from G0 to GAlert. HMGB1 also transitions human stem and progenitor cells to GAlert. Therefore, exogenous HMGB1 may benefit patients in many clinical scenarios, including trauma, chemotherapy, and elective surgery.

scholarly journals Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Melissa Lo Monaco ◽  
Greet Merckx ◽  
Jessica Ratajczak ◽  
Pascal Gervois ◽  
Petra Hilkens ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Outcome Measures ◽  
Cartilage Repair ◽  
Cartilage Tissue ◽  
Preclinical Studies ◽  
Paracrine Factors ◽  
Advantages And Disadvantages

Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recentin vitrodata and fromin vivopreclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

scholarly journals Efficacy of Mesenchymal Stromal Cells in Preclinical Models of Necrotizing Enterocolitis: a Systematic Review Protocol

2021 ◽  
Author(s):  
Camille Maltais-Bilodeau ◽  
Ewa Henckel ◽  
Kelly D. Cobey ◽  
Nadera Ahmadzai ◽  
Becky Skidmore ◽  
...  
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Necrotizing Enterocolitis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bowel Perforation ◽  
Risk Of Bias ◽  
Sufficient Evidence ◽  
Preclinical Models

Abstract BackgroundNecrotizing enterocolitis is an acute inflammatory disease of the intestine that can lead to necrosis and bowel perforation. It is a severe complication of preterm birth with a prevalence of 7% in infants with a birth weight less than 1500 grams. It’s mortality rate is up to 30% and survival after necrotizing enterocolitis leads to long-term gastrointestinal and neurocognitive consequences. The current treatment is supportive and includes bowel rest and decompression and antibiotics. Thus, new treatments are necessary to reduce mortality and morbidity. Mesenchymal stromal cells are known to have anti-inflammatory properties and might be a promising option for treatment. Here we present a protocol for a systematic review with the aim to explore the efficacy of cell therapies with mesenchymal stromal cells in animal models of necrotizing enterocolitis. The primary outcome is histological signs of necrotizing enterocolitis. Additional outcomes include survival, bowel perforation, gut permeability, gut motility, levels of inflammatory markers, cytokine levels and adverse events.MethodsWe will conduct a systematic search of MEDLINE, Embase, and Web of Science databases. The retrieved records will be screened individually by two investigators. We will include all preclinical in vivo animal models of experimentally induced NEC that evaluate the efficacy of mesenchymal stromal cells or other cell therapy treatments. Outcome data will be extracted from each article and risk of bias assessment performed. Funnel plots and SYRCLE’s risk of bias tool for animal studies will be used. Data will be reported as ratios, divided in predefined subgroups where relevant. DiscussionThis systematic review aims to examine the efficacy of mesenchymal stromal cells in preclinical models of necrotizing enterocolitis and whether there is sufficient evidence to support a clinical trial of efficacy and safety of the treatment with mesenchymal stromal cells in infants with necrotizing enterocolitis.Systematic review registrationThis protocol has been registered on Open Science framework: osf.io/5rc6t

scholarly journals Enhancement of Chondrogenesis in Hypoxic Precondition Culture: A Systematic Review

2021 ◽  
Vol 9 (F) ◽  
pp. 492-504
Author(s):  
Sholahuddin Rhatomy ◽  
Riky Setyawan ◽  
Michael Aaron Romulo
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Oxygen Level ◽  
Hypoxic Precondition ◽  
Online Library

BACKGROUND: Cartilage tear has begun to be treated with stem cells. However, stem cell oxygen level culture has not been evaluated for the best environment to enhance chondrogenesis. AIM: The purpose of this review is to focus on the hypoxic oxygen level of stem cells culture as a treatment for cartilage tear. METHODS: A literature search was systemically conducted on PubMed (MEDLINE), OVID, EMBASE, the Cochrane Library, Scopus, Web of Science, Science Direct, Wiley Online Library, Google Scholar, and bibliography of selected articles with the terms (“culture”) AND (“stem cell” OR “mesenchymal stem cell” OR “MSC”) AND (“hypoxic” OR “hypoxia”) AND (“cartilage” OR “chondro*”) as the main keywords. A total of 438 articles were reviewed. Thirty-six articles were considered relevant for this systematic review. RESULTS: The result of this review supports stimulation effects of hypoxic oxygen level stem cell culture in chondrogenesis process. Most studies used 5% oxygen concentration for culture, both of in vivo and in vitro studies. Due to the heterogeneity nature of the included studies, meta-analysis was unable to be conducted. CONCLUSION: Hypoxia state seems to play an important role in chondrocytes proliferation, differentiation, and matrix production.

scholarly journals The synthetic artificial stem cell (SASC): Shifting the paradigm of cell therapy in regenerative engineering

2022 ◽  
Vol 119 (2) ◽  
pp. e2116865118
Author(s):  
Shiv Shah ◽  
Caldon Jayson Esdaille ◽  
Maumita Bhattacharjee ◽  
Ho-Man Kan ◽  
Cato T. Laurencin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Therapeutic Strategy ◽  
Cartilage Degeneration ◽  
Biomechanical Properties ◽  
Adipose Derived Stem Cells ◽  
Rodent Models

Stem cells are of great interest in tissue regeneration due to their ability to modulate the local microenvironment by secreting bioactive factors (collectively, secretome). However, secretome delivery through conditioned media still requires time-consuming cell isolation and maintenance and also may contain factors antagonistic to targeted tissue regeneration. We have therefore engineered a synthetic artificial stem cell (SASC) system which mimics the paracrine effect of the stem cell secretome and provides tailorability of the composition for targeted tissue regeneration. We report the first of many applications of the SASC system we have formulated to treat osteoarthritis (OA). Choosing growth factors important to chondrogenesis and encapsulating respective recombinant proteins in poly (lactic-coglycolic acid) 85:15 (PLGA) we fabricated the SASC system. We compared the antiinflammatory and chondroprotective effects of SASC to that of adipose-derived stem cells (ADSCs) using in vitro interleukin 1B-induced and in vivo collagenase-induced osteoarthritis rodent models. We have designed SASC as an injectable therapy with controlled release of the formulated secretome. In vitro, SASC showed significant antiinflammatory and chondroprotective effects as seen by the up-regulation of SOX9 and reduction of nitric oxide, ADAMTS5, and PRG4 genes compared to ADSCs. In vivo, treatment with SASC and ADSCs significantly attenuated cartilage degeneration and improved the biomechanical properties of the articular cartilage in comparison to OA control. This SASC system demonstrates the feasibility of developing a completely synthetic, tailorable stem cell secretome which reinforces the possibility of developing a new therapeutic strategy that provides better control over targeted tissue engineering applications.

scholarly journals Effectiveness of mesenchymal stem cell-conditioned medium in bone regeneration in animal and human models: a systematic review and meta-analysis

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Maria Paula Benavides-Castellanos ◽  
Nathaly Garzón-Orjuela ◽  
Itali Linero
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Conditioned Medium ◽  
Meta Analysis ◽  
Bone Defects ◽  
Favorable Effect ◽  
Human Models ◽  
Regeneration Of Bone

Abstract Background Given the limitations of current therapies for the reconstruction of bone defects, regenerative medicine has arisen as a new therapeutic strategy along with mesenchymal stem cells (MSCs), which, because of their osteogenic potential and immunomodulatory properties, have emerged as a promising alternative for the treatment of bone injuries. In vivo studies have demonstrated that MSCs have a positive effect on regeneration due to their secretion of cytokines and growth factors that, when collected in conditioned medium (MSC-CM) and applied to an injured tissue, can modulate and promote the formation of new tissue. Objective To evaluate the effectiveness of application of conditioned medium derived from mesenchymal stem cells in bone regeneration in animal and human models. Methods We conducted a systematic review with a comprehensive search through February of 2018 using several electronic databases (MEDLINE, EMBASE, SCOPUS, CENTRAL (Ovid), and LILACS), and we also used the “snowballing technique”. Articles that met the inclusion criteria were selected through abstract review and subsequent assessment of the full text. We assessed the risk of bias with the SYRCLE and Cochrane tools, and three meta-analyses were performed. Results We included 21 articles, 19 of which used animal models and 2 of which used human models. In animal models, the application of MSC-CM significantly increased the regeneration of bone defects in comparison with control groups. Human studies reported early mineralization in regenerated bones, and no bone resorption, inflammation, nor local or systemic alterations were observed in any case. The meta-analysis showed an overall favorable effect of the application of MSC-CM. Conclusions The application of MSC-CM to bone defects has a positive and favorable effect on the repair and regeneration of bone tissue, particularly in animal models. It is necessary to perform additional studies to support the application of MSC-CM in clinical practice.

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