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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 -
Cureus Nov 2023Osteosarcoma (OS) is a debilitating cancer of the bone that commonly afflicts the young and old. This may be de novo or associated with tumorigenic syndromes. However,... (Review)
Review
Osteosarcoma (OS) is a debilitating cancer of the bone that commonly afflicts the young and old. This may be de novo or associated with tumorigenic syndromes. However, many molecular mechanisms are still being uncovered and may offer greater avenues for screening and therapy. Cadherins, including E-cadherin and N-cadherin/vimentin, are involved in epithelial-to-mesenchymal transmission (EMT), which is key for tumor invasion. A study reviewing the relationship between OS and cadherins might elucidate a potential target for therapy and screening. A robust literature review was conducted by searching PubMed with the keywords "osteosarcoma", "cadherin", "e-cadherin" and "n-cadherin". Of a preliminary 266 papers, 25 were included in the final review. Review articles and those without primary data were excluded. Loss of E-cadherin is noted in metastatic cell lines of osteosarcoma. Overexpression of E-cadherin or knockout of N-cadherin/vimentin results in loss of metastatic potential. There are several methods of gene knockout, including CRISPR-Cas9 gene editing, viral vector insertion with micro RNA complementary to long noncoding RNA within gene segments, or proteomic editing. Screening for EMT and genetic treatment of EMT is a possible avenue for the treatment of refractory osteosarcoma. Several studies were conducted ex vivo. Further testing involving in vitro therapy is necessary to validate these methods. Limitations of this study involve a lack of in vivo trials to validate methods.
PubMed: 38156135
DOI: 10.7759/cureus.49521 -
International Journal of Molecular... Dec 2023Papillary subtypes of renal-cell carcinoma (pRCC) represent 10-15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis... (Meta-Analysis)
Meta-Analysis
Papillary subtypes of renal-cell carcinoma (pRCC) represent 10-15% of the cases and commonly have MET alterations. This systematic review and single-arm meta-analysis evaluated MET inhibitor therapy (METi) efficacy and safety in adults with confirmed advanced pRCC. The search strategy included PubMed, Web-of-science, Cochrane, and Scopus. We used the DerSimonian/Laird random effect model for all analyses; -value < 5% was considered significant, and heterogeneity was assessed with I. Three clinical trials and six cohort studies were included with 504 patients; 31% were MET-driven. Our pooled analysis demonstrated an objective response rate (ORR) in MET-driven, MET-independent, and overall patients of: 36% (95%CI: 10-62), 0% (95%CI: 0-3), and 21% (95%CI: 1-41), respectively. One-year disease control and progression-free survival rates were, respectively, 70% (95%CI: 52-88) and 15% (95%CI: 10-20). Twelve- and twenty-four-month survival rates were, respectively, 43% (95%CI: 23-64) and 10% (95%CI: 0-30). The prevalence of adverse events of any grade and grades 3-5 were 96% (95%CI: 91-100) and 44% (95%CI: 37-50), respectively. We suggest METi has anti-tumor activity and is tolerable in patients with advanced pRCC.
Topics: Adult; Humans; Carcinoma, Renal Cell; Cohort Studies; Enzyme Therapy; Kidney Neoplasms; Protein Kinase Inhibitors
PubMed: 38139411
DOI: 10.3390/ijms242417582 -
Journal of Clinical Medicine Dec 2023Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to... (Review)
Review
BACKGROUND
Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to report the outcomes of the regenerative potential of MSCs in treating pressure ulcers, assessing the effectiveness of MSCs in treating pressure ulcers.
METHODS
A computerized search for articles on animal models that use MSCs as primary therapy to treat pressure ulcers, published from conception to present, was conducted using PubMed, MEDLINE, Embase, and CINAHL. Our search yielded 52 articles, narrowed to 44 after excluding duplicates.
RESULTS
Out of 52 articles collected from four databases, 11 met the inclusion criteria. A total of 11 articles published between 2008 and 2020 met the inclusion criteria. Eight studies were observational descriptive papers in animal models, and three were prospective. Six studies used autologous MSCs, while five used allogenic MSCs. Three studies were conducted in humans, and the remaining eight were conducted in animals. The most common method of cell delivery was an intradermal injection in the margins of the ulcer. All studies reported positive results, including improved wound healing, reduced inflammation, and improved tissue regeneration.
CONCLUSIONS
MSCs have shown promising results in treating pressure ulcers in animal and clinical trials. The combination of MSCs and scaffold materials has also been studied and found to be effective in wound healing. A standardized human wound model has been proposed further to investigate the efficacy of cell-based therapies for chronic wounds. However, more research is needed to determine the best quantity of cells to apply for pressure ulcers and to ensure the safety and efficacy of these treatments in clinical settings.
PubMed: 38137625
DOI: 10.3390/jcm12247545 -
Veterinary Sciences Nov 2023Musculoskeletal injuries in horses have a great economic impact, predominantly affecting tendons, ligaments, and cartilage, which have limited natural regeneration. Cell... (Review)
Review
Musculoskeletal injuries in horses have a great economic impact, predominantly affecting tendons, ligaments, and cartilage, which have limited natural regeneration. Cell therapy, which uses mesenchymal stem cells due to their tissue differentiation properties and anti-inflammatory and immunoregulatory effects, aims to restore damaged tissue. In this manuscript, we performed a systematic review using the Parsifal tool, searching the PubMed and Web of Science databases for articles on regenerative medicine for equine musculoskeletal injuries. Our review covers 17 experimental clinical studies categorized by the therapeutic approach used: platelet-rich plasma, conditioned autologous serum, mesenchymal stem cells, and secretome. These therapies reduce healing time, promote regeneration of fibrocartilaginous tissue, improve cellular organization, and improve joint functionality and sustainability. In conclusion, regenerative therapies using platelet-rich plasma, conditioned autologous serum, equine mesenchymal stem cells, and the emerging field of the secretome represent a promising and highly effective approach for the treatment of joint pathologies in horses, implying a valuable advance in equine healthcare.
PubMed: 38133217
DOI: 10.3390/vetsci10120666 -
Neural Regeneration Research Jul 2024Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may...
Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may improve symptoms, no treatment can cure or reverse the disease itself. Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson's disease. Mesenchymal stem cells are considered a promising option due to fewer ethical concerns, a lower risk of immune rejection, and a lower risk of teratogenicity. We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function, memory, and preservation of dopaminergic neurons in a Parkinson's disease animal model. We searched bibliographic databases (PubMed/MEDLINE, Embase, CENTRAL, Scopus, and Web of Science) to identify articles and included only peer-reviewed in vivo interventional animal studies published in any language through June 28, 2023. The study utilized the random-effect model to estimate the 95% confidence intervals (CI) of the standard mean differences (SMD) between the treatment and control groups. We use the systematic review center for laboratory animal experimentation's risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment. A total of 33 studies with data from 840 Parkinson's disease model animals were included in the meta-analysis. Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test. Among the stem cell types, the bone marrow MSCs with neurotrophic factor group showed largest effect size (SMD [95% CI] = -6.21 [-9.50 to -2.93], P = 0.0001, I2 = 0.0 %). The stem cell treatment group had significantly more tyrosine hydroxylase positive dopaminergic neurons in the striatum ([95% CI] = 1.04 [0.59 to 1.49], P = 0.0001, I2 = 65.1 %) and substantia nigra (SMD [95% CI] = 1.38 [0.89 to 1.87], P = 0.0001, I2 = 75.3 %), indicating a protective effect on dopaminergic neurons. Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route (SMD [95% CI] = -2.59 [-3.25 to -1.94], P = 0.0001, I2 = 74.4 %). The memory test showed significant improvement only in the intravenous route (SMD [95% CI] = 4.80 [1.84 to 7.76], P = 0.027, I2 = 79.6 %). Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson's disease. Further research is required to determine the optimal stem cell types, modifications, transplanted cell numbers, and delivery methods for these protocols.
PubMed: 38051903
DOI: 10.4103/1673-5374.387976 -
Systematic Reviews Nov 2023Stem cell sheet implantation offers a promising avenue for spinal cord injury (SCI) and is currently under investigation in pre-clinical in vivo studies. Nevertheless, a...
BACKGROUND
Stem cell sheet implantation offers a promising avenue for spinal cord injury (SCI) and is currently under investigation in pre-clinical in vivo studies. Nevertheless, a systematic review of the relevant literature is yet to be performed. Thus, this systematic review aims to explore the efficacy of stem cell sheet technology in treating SCI, as indicated by experimental animal model studies.
METHODS
We searched PubMed, EMBASE, and Web of Science. Manuscripts that did not pertain to in vivo pre-clinical studies and those published in non-English languages were excluded. A risk assessment for bias was performed using the SYRCLE tool. Extracted data were synthesized only qualitatively because the data were not suitable for conducting the meta-analysis.
RESULTS
Among the 847 studies retrieved from electronic database searches, seven met the inclusion criteria. Six of these studies employed a complete transection model, while one utilized a compression model. Stem cell sources included bone marrow mesenchymal stem cells, stem cells from human exfoliated deciduous teeth, and adipose-derived mesenchymal stem cells. In all included studies, stem cell sheet application significantly improved motor and sensory functional scores compared to intreated SCI rats. This functional recovery correlated with histological improvements at the injury site. All studies are at low risk of bias but certain domains were not reported by some or all of the studies.
CONCLUSION
The results of our systematic review suggest that stem cell sheets may be a feasible therapeutic approach for the treatment of SCI. Future research should be conducted on stem cell sheets in various animal models and types of SCI, and careful validation is necessary before translating stem cell sheets into clinical studies.
Topics: Animals; Humans; Rats; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Spinal Cord Injuries
PubMed: 38037129
DOI: 10.1186/s13643-023-02390-3 -
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 -
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 -
European Journal of Dentistry Nov 2023Recent evidence suggests the immense potential of human mesenchymal stem cell (hMSC) secretome conditioned medium-mediated augmentation of angiogenesis. However,...
Recent evidence suggests the immense potential of human mesenchymal stem cell (hMSC) secretome conditioned medium-mediated augmentation of angiogenesis. However, angiogenesis potential varies from source and origin. The hMSCs derived from the oral cavity share an exceptional quality due to their origin from a hypoxic environment. Our systematic review aimed to compare the mesenchymal stem cells (MSCs) derived from various oral cavity sources and cell-derived secretomes, and evaluate their angiogenic potential. A literature search was conducted using PubMed and Scopus from January 2000 to September 2020. Source-wise outcomes were systematically analyzed using , , and studies, emphasizing endothelial cell migration, tube formation, and blood vessel formation. Ninety-four studies were included in the systematic review, out of which 4 studies were subsequently included in the meta-analysis. Prominent growth factors and other bioactive components implicated in improving angiogenesis were included in the respective studies. The findings suggest that oral tissues are a rich source of hMSCs. The meta-analysis revealed a positive correlation between dental pulp-derived MSCs (DPMSCs) and stem cells derived from apical papilla (SCAP) compared to human umbilical cord-derived endothelial cell lines as a control. It shows a statistically significant positive correlation between the co-culture of human umbilical vein endothelial cells (HUVECs) and DPMSCs with tubule length formation and total branching points. Our meta-analysis revealed that oral-derived MSCs (dental pulp stem cells and SCAP) carry a better angiogenic potential than endothelial cell lines alone. The reviewed literature illustrates that oral cavity-derived MSCs (OC-MSCs) increased angiogenesis. The present literature reveals a dearth of investigations involving sources other than dental pulp. Even though OC-MSCs have revealed more significant potential than other MSCs, more comprehensive, target-oriented interinstitutional prospective studies are warranted to determine whether oral cavity-derived stem cells are the most excellent sources of significant angiogenic potential.
PubMed: 37995732
DOI: 10.1055/s-0043-1776315