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International Journal of Stem Cells Nov 2023Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal... (Review)
Review
Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.
PubMed: 38016704
DOI: 10.15283/ijsc23092 -
Pediatric Research Jan 2024Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-term complications. Mesenchymal stem cells (MSCs) have emerged as a novel therapeutic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-term complications. Mesenchymal stem cells (MSCs) have emerged as a novel therapeutic agent. This systematic review aims to determine the effects of stem cell-based interventions for the treatment of PAIS in preclinical studies.
METHODS
We included all controlled studies on MSCs in neonatal animals with PAIS. Functional outcome was the primary outcome. The literature search was performed in February 2021.
RESULTS
In the 20 included studies, MSCs were most frequently delivered via intracerebral injection (n = 9), 3 days after the induction of PAIS (n = 8), at a dose ranging from 5 × 10 to 5 × 10 cells. The meta-analysis showed an improvement on the cylinder rearing test (MD: -10.62; 95% CI: -14.38 to -6.86) and on the water maze test (MD: 1.31 MD; 95% CI: 0.80 to 1.81) in animals treated with MSCs compared to the control group animals.
CONCLUSION
MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured animals; however, the certainty of the evidence is low. Registration of the protocol of preclinical studies, appropriate sample size calculation, rigorous randomization, and reporting of the data on animal sex and survival are warranted. PROSPERO registration number: CRD42021239642.
IMPACT
This is the first systematic review and meta-analysis of preclinical studies investigating the effects of MSCs in an experimental model of PAIS. MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured neonatal animals. The certainty of the evidence is low due to high or unclear risk of bias in most domains.
Topics: Animals; Female; Pregnancy; Brain Ischemia; Infant, Newborn, Diseases; Ischemic Stroke; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Research Design; Stroke
PubMed: 35906311
DOI: 10.1038/s41390-022-02208-3 -
International Journal of Molecular... Jun 2024The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the... (Review)
Review
The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the treatment of ischemic heart damage. Following PRISMA guidelines, we conducted electronic searches in MEDLINE, and EMBASE. We screened 592 studies, and included RCTs, observational studies, and cohort studies that examined the effect of hematopoietic stem cell therapy in adult patients with heart failure. Studies that involved pediatric patients, mesenchymal stem cell therapy, and non-heart failure (HF) studies were excluded from our review. Out of the 592 studies, 7 studies met our inclusion criteria. Overall, administration of hematopoietic stem cells (via intracoronary or myocardial infarct) led to positive cardiac outcomes such as improvements in pathological left-ventricular remodeling, perfusion following acute myocardial infarction, and NYHA symptom class. Additionally, combined death, rehospitalization for heart failure, and infarction were significantly lower in patients treated with bone marrow-derived hematopoietic stem cells. Our review demonstrates that hematopoietic stem cell administration can lead to positive cardiac outcomes for HF patients. Future studies should aim to increase female representation and non-ischemic HF patients.
Topics: Humans; Heart Failure; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Treatment Outcome
PubMed: 38928341
DOI: 10.3390/ijms25126634 -
PloS One 2023Unexplained recurrent spontaneous abortion (URSA) remains an intractable reproductive dilemma due to the lack of understanding of the pathogenesis. This study aimed to...
OBJECTIVES
Unexplained recurrent spontaneous abortion (URSA) remains an intractable reproductive dilemma due to the lack of understanding of the pathogenesis. This study aimed to evaluate the preclinical evidence for the mesenchymal stromal cell (MSC) treatment for URSA.
METHODS
A meticulous literature search was independently performed by two authors across the Cochrane Library, EMBASE, and PubMed databases from inception to April 9, 2023. Each study incorporated was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. The amalgamated standardized mean difference (SMD) accompanied by 95% confidence interval (CI) were deduced through a fixed-effects or random-effects model analysis.
RESULTS
A total of ten studies incorporating 140 mice were subjected to data analysis. The MSC treatment yielded a significant reduction in the abortion rate within the URSA model (OR = 0.23, 95%CI [0.17, 0.3], P<0.00001). Moreover, it elicited a positive modulatory impact on the expression profiles of several inflammatory cytokines in the decidual tissue of URSA murine models, inclusive of IL4 (SMD 1.63, 95% CI [0.39, 2.86], P = 0.01), IL10 (SMD 1.60, 95% CI [0.58, 2.61], P = 0.002), IFN-γ (SMD -1.66, 95%CI [-2.79, -0.52], P = 0.004), and TNF-α (SMD -1.98, 95% CI [-2.93, -1.04], P< 0.0001). Subgroup analyses underscored that the administration mode of intraperitoneal and uterine horn injections, and sources of bone MSCs and adipose-derived MSCs contributed positively to the expression of IL4, IL10, and decreased the expression of IFN-γ in decidual tissue of URSA (P<0.05). Conversely, the tail vein injections subgroup was observed with no statistical significance (P>0.05).
CONCLUSIONS
The findings underscore the considerable potential of MSCs in URSA therapy. Nonetheless, the demand for enhanced transparency in research design and direct comparisons between various MSC sources and administration routes in URSA is paramount to engendering robust evidence that could pave the way for successful clinical translation.
Topics: Animals; Female; Humans; Mice; Pregnancy; Abortion, Habitual; Abortion, Spontaneous; Cytokines; Interleukin-10; Interleukin-4; Mesenchymal Stem Cells; Meta-Analysis as Topic
PubMed: 38011163
DOI: 10.1371/journal.pone.0294855 -
Indian Journal of Anaesthesia Nov 2023Cancer is a leading cause of mortality worldwide. Despite advancements in cancer management, cancer progression remains a challenge, requiring the development of novel...
BACKGROUND AND AIMS
Cancer is a leading cause of mortality worldwide. Despite advancements in cancer management, cancer progression remains a challenge, requiring the development of novel therapies. Midazolam is a commonly used adjunct to anaesthesia care for various surgeries, including cancer. Recently, there has been a growing interest in exploring the potential role of midazolam as an anticancer agent; however, the exact mechanism of this linkage is yet to be investigated thoroughly.
METHODS
Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, this systematic review presented aggregated evidence (till November 2022) of the effects of midazolam on cancer progression and survival. All primary research article types where midazolam was administered or on subjects with cancers were included. No restrictions were applied on routes of administration or the type of cancer under investigation. Narrative synthesis depicted qualitative findings, whereas frequencies and percentages presented numerical data.
RESULTS
Of 1720 citations, 19 studies were included in this review. All articles were preclinical studies conducted either (58%, 11/19) or both and (42%, 8/19). The most studied cancer was lung carcinoma (21%, 4/19). There are two main findings in this review. First, midazolam delays cancer progression (89%, 17/19). Second, midazolam reduces cancer cell survival (63%, 12/19). The two major mechanisms of these properties can be explained via inducing apoptosis (63%, 12/19) and inhibiting cancer cell proliferation (53%, 10/19). In addition, midazolam demonstrated antimetastatic properties via inhibition of cancer invasion (21%, 4/19), migration (26%, 5/19), or epithelial-mesenchymal transition (5%, 1/19). These anticancer properties of midazolam were demonstrated through different pathways when midazolam was used alone or in combination with traditional cancer chemotherapeutic agents.
CONCLUSION
This systematic review highlights that midazolam has the potential to impede cancer progression and decrease cancer cell survival. Extrapolation of these results into human cancer necessitates further investigation.
PubMed: 38213688
DOI: 10.4103/ija.ija_731_23 -
Journal of Nanobiotechnology Apr 2024Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on... (Review)
Review
Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research.
Topics: Osteogenesis; Endothelial Cells; Bone Regeneration; Osteoclasts; Nanostructures; Cell Differentiation
PubMed: 38627717
DOI: 10.1186/s12951-024-02442-3 -
Biomedicines Apr 2024Achilles tendon (AT) pathologies are common musculoskeletal conditions that can significantly impair function. Despite various traditional treatments, recovery is often... (Review)
Review
Achilles tendon (AT) pathologies are common musculoskeletal conditions that can significantly impair function. Despite various traditional treatments, recovery is often slow and may not restore full functionality. The use of extracellular vesicles (EVs) has emerged as a promising therapeutic option due to their role in cell signaling and tissue regeneration. This systematic review aims to consolidate current in vivo animal study findings on the therapeutic effects of EVs on AT injuries. An extensive literature search was conducted using the PubMed, Scopus, and Embase databases for in vivo animal studies examining the effects of EVs on AT pathologies. The extracted variables included but were not limited to the study design, type of EVs used, administration methods, efficacy of treatment, and proposed therapeutic mechanisms. After screening, 18 studies comprising 800 subjects were included. All but one study reported that EVs augmented wound healing processes in the AT. The most proposed mechanisms through which this occurred were gene regulation of the extracellular matrix (ECM), the enhancement of macrophage polarization, and the delivery of therapeutic microRNAs to the injury site. Further research is warranted to not only explore the therapeutic potential of EVs in the context of AT pathologies, but also to establish protocols for their clinical application.
PubMed: 38790904
DOI: 10.3390/biomedicines12050942 -
Experimental & Molecular Medicine Feb 2024The harmful effects of fine particulate matter ≤2.5 µm in size (PM) on human health have received considerable attention. However, while the impact of PM on the... (Review)
Review
The harmful effects of fine particulate matter ≤2.5 µm in size (PM) on human health have received considerable attention. However, while the impact of PM on the respiratory and cardiovascular systems has been well studied, less is known about the effects on stem cells in the bone marrow (BM). With an emphasis on the invasive characteristics of PM, this review examines the current knowledge of the health effects of PM exposure on BM-residing stem cells. Recent studies have shown that PM enters the circulation and then travels to distant organs, including the BM, to induce oxidative stress, systemic inflammation and epigenetic changes, resulting in the reduction of BM-residing stem cell survival and function. Understanding the broader health effects of air pollution thus requires an understanding of the invasive characteristics of PM and its direct influence on stem cells in the BM. As noted in this review, further studies are needed to elucidate the underlying processes by which PM disturbs the BM microenvironment and inhibits stem cell functionality. Strategies to prevent or ameliorate the negative effects of PM exposure on BM-residing stem cells and to maintain the regenerative capacity of those cells must also be investigated. By focusing on the complex relationship between PM and BM-resident stem cells, this review highlights the importance of specific measures directed at safeguarding human health in the face of rising air pollution.
Topics: Humans; Particulate Matter; Air Pollutants; Bone Marrow; Air Pollution; Mesenchymal Stem Cells; Environmental Exposure
PubMed: 38200155
DOI: 10.1038/s12276-023-01149-z -
Brazilian Journal of Medical and... 2024One of the main challenges of tissue engineering in dentistry is to replace bone and dental tissues with strategies or techniques that simulate physiological tissue...
Influence of the addition of nanohydroxyapatite to scaffolds on proliferation and differentiation of human mesenchymal stem cells: a systematic review of in vitro studies.
One of the main challenges of tissue engineering in dentistry is to replace bone and dental tissues with strategies or techniques that simulate physiological tissue repair conditions. This systematic review of in vitro studies aimed to evaluate the influence of the addition of nanohydroxyapatite (NHap) to scaffolds on cell proliferation and osteogenic and odontogenic differentiation of human mesenchymal stem cells. In vitro studies on human stem cells that proliferated and differentiated into odontogenic and osteogenic cells in scaffolds containing NHap were included in this study. Searches in PubMed/MEDLINE, Scopus, Web of Science, OpenGrey, ProQuest, and Cochrane Library electronic databases were performed. The total of 333 articles was found across all databases. After reading and analyzing titles and abstracts, 8 articles were selected for full reading and extraction of qualitative data. Results showed that despite the large variability in scaffold composition, NHap-containing scaffolds promoted high rates of cell proliferation, increased alkaline phosphatase (ALP) activity during short culture periods, and induced differentiation, as evidenced by the high expression of genes involved in osteogenesis and odontogenesis. However, further studies with greater standardization regarding NHap concentration, type of scaffolds, and evaluation period are needed to observe possible interference of these criteria in the action of NHap on the proliferation and differentiation of human stem cells.
Topics: Humans; Cell Differentiation; Cell Proliferation; Data Accuracy; Mesenchymal Stem Cells; Pyrenes
PubMed: 38265343
DOI: 10.1590/1414-431X2023e13105 -
Cellular & Molecular Biology Letters Jan 2024Burn injuries can be associated with prolonged healing, infection, a substantial inflammatory response, extensive scarring, and eventually death. In recent decades, both...
BACKGROUND
Burn injuries can be associated with prolonged healing, infection, a substantial inflammatory response, extensive scarring, and eventually death. In recent decades, both the mortality rates and long-term survival of severe burn victims have improved significantly, and burn care research has increasingly focused on a better quality of life post-trauma. However, delayed healing, infection, pain and extensive scar formation remain a major challenge in the treatment of burns. ADSCs, a distinct type of mesenchymal stem cells, have been shown to improve the healing process. The aim of this review is to evaluate the efficacy of ADSCs in the treatment of burn injuries.
METHODS
A systematic review of the literature was conducted using the electronic databases PubMed, Web of Science and Embase. The basic research question was formulated with the PICO framework, whereby the usage of ADSCs in the treatment of burns in vivo was determined as the fundamental inclusion criterion. Additionally, pertinent journals focusing on burns and their treatment were screened manually for eligible studies. The review was registered in PROSPERO and reported according to the PRISMA statement.
RESULTS
Of the 599 publications screened, 21 were considered relevant to the key question and were included in the present review. The included studies were almost all conducted on rodents, with one exception, where pigs were investigated. 13 of the studies examined the treatment of full-thickness and eight of deep partial-thickness burn injuries. 57,1 percent of the relevant studies have demonstrated that ADSCs exhibit immunomodulatory effects during the inflammatory response. 16 studies have shown improved neovascularisation with the use of ADSCs. 14 studies report positive influences of ADSCs on granulation tissue formation, while 11 studies highlight their efficacy in promoting re-epithelialisation. 11 trials demonstrated an improvement in outcomes during the remodelling phase.
CONCLUSION
In conclusion, it appears that adipose-derived stem cells demonstrate remarkable efficacy in the field of regenerative medicine. However, the usage of ADSCs in the treatment of burns is still at an early experimental stage, and further investigations are required in order to examine the potential usage of ADSCs in future clinical burn care.
Topics: Animals; Adipocytes; Burns; Mesenchymal Stem Cells; Quality of Life; Swine; Wound Healing
PubMed: 38182971
DOI: 10.1186/s11658-023-00526-w