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Stem Cells Translational Medicine Oct 2023Neonatal cell therapy applications are increasing; however, data on allogeneic cell therapy are limited.
BACKGROUND
Neonatal cell therapy applications are increasing; however, data on allogeneic cell therapy are limited.
OBJECTIVE
To summarize evidence on allogeneic cell therapy in term and preterm neonates.
METHODS
Cochrane Central Register of Controlled Trials, Embase, Ovid Medline, and various registries were searched for studies investigating the safety, feasibility, and efficacy of allogeneic cell therapy in neonates. Two authors independently selected the articles, extracted data, and assessed the risk of bias.
RESULTS
Twelve published (153 infants) and 21 ongoing studies were included. These studies predominantly sourced allogeneic cells from umbilical cord blood (UCB). Mesenchymal stromal cells (MSCs) were the main cell type used (134 of 153 infants); others included UCB-derived total nucleated cells (TNCs) and human amnion epithelial cells (hAECs). Applications included bronchopulmonary dysplasia (BPD; 113 infants), Krabbe disease (13 infants), intraventricular haemorrhage (10 infants), perinatal arterial ischemic stroke (10 infants), hypoxic-ischaemic encephalopathy (6 infants), and necrotizing enterocolitis (1 infant). Nine out of 12 studies did not report any serious adverse events (SAEs) related to cell administration. Three studies reported SAEs, such as graft versus host disease (GVHD) in 5 infants (UCB-derived TNCs for Krabbe disease); and transient cardiorespiratory compromise in 1 infant (hAECs for BPD). Data on efficacy outcomes were limited.
CONCLUSION
The safety and feasibility of allogeneic cell therapy applications in neonates are available, mainly from the use of MSCs. Further safety data for other cell types are required, and the risk of GVHD in different settings needs to be determined. Efficacy studies are largely lacking for all cell types.
PROTOCOL REGISTRATION
The protocol was registered with PROSPERO (registration number CRD42023397876), the international prospective register for systematic reviews (https://www.crd.york.ac.uk/PROSPERO).
PubMed: 37603845
DOI: 10.1093/stcltm/szad048 -
Journal of Orthopaedic Surgery and... Aug 2023The onset of OA is affected by a variety of factors, which eventually lead to the loss of cartilage in the joints, the formation of osteophytes, the loss of normal knee... (Meta-Analysis)
Meta-Analysis
PURPOSE
The onset of OA is affected by a variety of factors, which eventually lead to the loss of cartilage in the joints, the formation of osteophytes, the loss of normal knee mobility, and pain and discomfort, which seriously affects the quality of life. HUC-MSCs can promote cartilage production and have been widely used in research in the past decade. This article systematically summarizes that it is well used in basic research and clinical studies to promote inflammatory chondrogenesis in the treatment of OA. Provide a theoretical basis for clinical treatment.
PATIENTS AND METHODS
This study collected CNKI, Wanfang, PubMed, and articles related to the treatment of OA with HUC-MSCs since their publication, excluding non-basic and clinical studies such as reviews and meta-analysis. A total of 31 basic experimental studies and 12 clinical studies were included. Systematically analyze the effects of HUC-MSCs on inhibiting inflammatory factors, promoting chondrocyte production, and current clinical treatment.
RESULTS
HUC-MSCs can reduce inflammatory factors such as MMP-13, ADAMTS-5, IL-1β, IL-1, IL-6, TNF-α, induced conversion from M1 to M2 in OA to protect cartilage damage and reduce OA inflammation. Synthesize ColII, SOX9, and aggrecan at the same time to promote cartilage synthesis.
CONCLUSION
HUC-MSCs not only have typical stem cell biological characteristics, but also have rich sources and convenient material extraction. Compared with stem cells from other sources, HUC-MSCs have stronger proliferation, differentiation, and immune regulation abilities. Furthermore, there are no ethical issues associated with their use.
SAFETY
Primarily attributed to pain, the majority of individuals experience recovery within 24 h following injection. HUC-MSCs possess the ability to alleviate pain, enhance knee joint function, and potentially postpone the need for surgical intervention in both non-surgical and other cases, making them highly deserving of clinical promotion and application.
Topics: Humans; Osteoarthritis, Knee; Chondrogenesis; Quality of Life; Knee Joint; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 37644595
DOI: 10.1186/s13018-023-04131-7 -
Sports Medicine and Arthroscopy Review Sep 2023Highly prone to injury, the rotator cuff greatly contributes to the stability and mobility of the shoulder. Clinicians prioritize conservative treatment, resorting to...
Highly prone to injury, the rotator cuff greatly contributes to the stability and mobility of the shoulder. Clinicians prioritize conservative treatment, resorting to surgery only when necessary, although they are hindered by inherent limitations. Biological therapies, including perinatal tissue, such as umbilical cord (UC) tissue, hold promise for treating rotator cuff injuries (RCIs) in the field of regenerative medicine. This article qualitatively presents the in vitro, preclinical, clinical, and ongoing scientific literature exploring the application of UC tissue and associated mesenchymal stem cells in the context of RCIs. Employing the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines, a systematic review was conducted. These studies have presented substantial evidence indicating that UC tissue and UC-derived mesenchymal stem cells are safe and potentially efficacious for managing RCIs, though more adequately powered randomized controlled trials are warranted to further establish efficacy and justify clinical use.
Topics: Humans; Rotator Cuff Injuries; Rotator Cuff; Mesenchymal Stem Cells; Arthroscopy; Umbilical Cord; Treatment Outcome
PubMed: 37976128
DOI: 10.1097/JSA.0000000000000369 -
Tissue Engineering and Regenerative... Dec 2023Secretome provides promising potential in replacing cell-based therapies in wound repair therapy. This study aimed to systematically review and conduct a meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Secretome provides promising potential in replacing cell-based therapies in wound repair therapy. This study aimed to systematically review and conduct a meta-analysis on the effectiveness of secretome in promoting wound healing.
METHODS
To ensure the rigor and transparency of our study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, as registered in PROSPERO with ID: CRD42023412671. We conducted a comprehensive search on four electronic databases to identify studies evaluating the effect of secretome on various clinical parameters of wound repair. In addition, we evaluated the risk of bias for each study using the Jadad and Newcastle-Ottawa scale. To synthesize the data, we employed a fixed-effects model and calculated the mean difference or odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
Based on six included articles, secretome is known to affect several clinical parameters in wound healing included the size and depth of ulcers during healing; the E´chelle d'évaluation clinique des cicatrices d'acne (ECCA) score, epidermal thickness, collagen fibers, abnormal elastic tissues, volume of atrophic acne scars, skin pore volume, and erythema during acne scar healing; and microcrust areas, erythema index, transepidermal water loss, volume of atrophic acne scars, erythema, and relative gene expression of procollagen type I, procollagen type III, and elastin were evaluated in wound healing after laser treatment. Meta-analysis studies showed that secretome reduced ulcer size (mean difference: 0.87, 95% CI of 0.37-1.38, p = 0.0007), decreased ulcer depth (mean difference: 0.18, 95% CI of 0.11-0.25, p < 0.00001), and provided patient satisfaction (odds ratio: 9.71, 95% CI of 3.47-21.17, p < 0.0001). However, secretome failed to reach significance in clinical improvement (OR 0.38, 95% CI 0.10, 1.53, p = 0.06).
CONCLUSION
The secretome provides good effectiveness in accelerating wound healing through a mechanism that correlates with several clinical parameters of wound repair.
Topics: Humans; Acne Vulgaris; Cicatrix; Erythema; Secretome; Ulcer
PubMed: 37682505
DOI: 10.1007/s13770-023-00570-9 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal... (Review)
Review
INTRODUCTION
Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed.
MATERIALS AND METHODS
Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed.
RESULTS
From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias.
CONCLUSIONS
This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays.
Topics: Adult; Humans; Kidney Transplantation; Living Donors; Immune Tolerance; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Transplantation Tolerance
PubMed: 37709652
DOI: 10.1016/j.trre.2023.100792 -
Sexual Medicine Reviews Dec 2023Erectile dysfunction (ED) is a common condition that negatively affects men's quality of life. It can have various causes, including psychological, vascular, and...
INTRODUCTION
Erectile dysfunction (ED) is a common condition that negatively affects men's quality of life. It can have various causes, including psychological, vascular, and neurologic factors. Existing treatments for ED mainly focus on symptom relief rather than addressing the underlying cause. Stem cells (SCs) have shown potential as a therapeutic approach for ED due to their anti-inflammatory properties.
OBJECTIVES
This systematic review aims to assess the current status of trials and determine the potential impact of SCs on male sexual health.
METHODS
A comprehensive search strategy was employed to gather relevant articles from 6 electronic databases. The search included articles published until March 2023. The reference lists of articles were manually reviewed to identify additional studies of relevance. The eligibility criteria for inclusion in the analysis focused on clinical trials involving humans that evaluated the safety and efficacy of SC therapy for ED. Exclusion criteria encompassed case reports, case series, abstracts, reviews, and editorials, as well as studies involving animals or SC derivatives. Data extraction was performed via a standardized form with a focus on erectile outcomes.
RESULTS
A total of 2847 articles were initially identified; 18 were included in the final analysis. These studies involved 373 patients with ED and various underlying medical conditions. Multiple types of SC were utilized in the treatment of ED: mesenchymal SCs, placental matrix-derived mesenchymal SCs, mesenchymal SC-derived exosomes, adipose-derived SCs, bone marrow-derived mononuclear SCs, and umbilical cord blood SCs.
CONCLUSION
SC therapy shows promise as an innovative and safe treatment for organic ED. However, the lack of standardized techniques and controlled groups in many studies hampers the ability to evaluate and compare trials.
Topics: Female; Pregnancy; Animals; Male; Humans; Erectile Dysfunction; Quality of Life; Placenta; Stem Cell Transplantation; Penile Erection
PubMed: 37758225
DOI: 10.1093/sxmrev/qead040 -
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 -
Cancers Jul 2023Lung cancer represents the leading cause of annual cancer-related deaths worldwide, accounting for 12.9%. The available treatment options for patients who experience... (Review)
Review
Lung cancer represents the leading cause of annual cancer-related deaths worldwide, accounting for 12.9%. The available treatment options for patients who experience disease progression remain limited. Targeted therapeutic approaches are promising but further understanding of the role of genetic alterations in tumorigenesis is imperative. The gene has garnered great interest in this regard. The aim of this systematic review was to analyze the findings from multiple studies to provide a comprehensive and unbiased summary of the evidence. A systematic search was conducted in the reputable scientific databases Embase and PubMed, leading to the inclusion of twenty-two articles, following the PRISMA guidelines, elucidating the biological role of in lung cancer and targeted therapies. The systematic review was registered in PROSPERO with registration ID: CRD42023437714. mutations were detected in 7.6-11.0% of cases while gene amplification was observed in 3.9-22.0%. Six studies showed favorable treatment outcomes utilizing inhibitors compared to standard treatment or placebo, with increases in PFS and OS ranging from 0.9 to 12.4 and 7.2 to 24.2 months, respectively, and one study reporting an increase in ORR by 17.3%. Furthermore, patients with a higher mutational burden may derive greater benefit from treatment with tyrosine kinase inhibitors (TKIs) than those with a lower mutational burden. Conversely, two studies reported no beneficial effect from adjunctive treatment with a targeted therapy. Given these findings, there is an urgent need to identify effective therapeutic strategies specifically targeting the gene in lung cancer patients.
PubMed: 37568643
DOI: 10.3390/cancers15153827 -
Dentistry Journal Oct 2023The aim of this systematic review is to describe and identify the prospects of β-Tricalcium Phosphate (β-TCP) as an alveolar bone grafting (ABG) material in cleft... (Review)
Review
The aim of this systematic review is to describe and identify the prospects of β-Tricalcium Phosphate (β-TCP) as an alveolar bone grafting (ABG) material in cleft lip/palate (CL/P) or alveolar bone cleft defects. A systematic review protocol based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020) was drafted. The literature search was conducted using MEDLINE/PubMed, Web of Science/ISI Web of Knowledge, Scopus, and the Cochrane Library, with English as the inclusion criterion and no publication year limits. The keywords yielded a total of 5824 publications. After removing duplicates and non-English articles, there were 3196 suitable articles available for evaluation. Subsequently, 1315 studies remained after reviewing titles and abstracts. Furthermore, 85 full articles were assessed for eligibility. After reading the complete texts of those papers, 20 were eventually selected that matched the inclusion requirements. Thirteen out of the twenty studies included in this systematic review were deemed to have a low risk of bias; one had a high risk of bias; and six had a moderate risk of bias due to not reporting randomization. β-TCP, when used as an ABG material, is biocompatible, visible, practical, offers a less invasive procedure, and does not interfere with orthodontic treatment. Synthetic β-TCP for ABG can be an alternative to autologous bone grafts under certain terms and conditions. The efficacy of β-TCP for ABG in CL/P or alveolar bone cleft defects can be enhanced through a tissue engineering approach that combines β-TCP with growth factors, mesenchymal stem cells, or other graft materials, along with modifications to β-TCP's physical properties.
PubMed: 37886919
DOI: 10.3390/dj11100234 -
BMC Oral Health Jul 2023Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects, which eventually lead to tooth loss. In recent years, stem cell-based therapy for periodontitis has been gradually applied to the clinic, but whether stem cell-based therapy plays a positive role in periodontal regeneration is unclear at present.
METHODS
The clinical studies related to the evaluation of mesenchymal stem cells for periodontal regeneration in PubMed, Cochrane Central Register of Controlled trials (CENTRAL), Web of Science (WOS), Embase, Scopus, Wanfang and China national knowledge infrastructure (CNKI) databases were searched in June 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell free therapy for the treatment periodontitis, and to have a follow-up for at least six months. Two evaluators searched, screened, and assessed the quality and the risk of bias in the included studies independently. Review Manager 5.4 software was used to perform the meta-analysis, and GRADEpro GDT was used to evaluate the level of the evidence.
RESULTS
Five randomized controlled trials (RCTs) including 118 patients were analyzed. The results of this meta-analysis demonstrated that stem cell-based therapy showed better therapeutic effects on clinical attachment level (CAL) (MD = - 1.18, 95% CI = - 1.55, - 0.80, P < 0.00001), pocket probing depth (PPD) (MD = - 0.75, 95% CI = - 1.35, - 0.14, P = 0.020), and linear distance from bone crest to bottom of defect (BC-BD)( MD = - 0.95, 95% CI = - 1.67, - 0.23, P = 0.010) compared with cell-free group. However, stem cell-based therapy presented insignificant effects on gingival recession (P = 0.14), linear distance from cementoenamel junction to bottom of defect (P = 0.05).
CONCLUSION
The results demonstrate that stem cell-based therapy may be beneficial for CAL, PPD and BC-BD. Due to the limited number of studies included, the strength of the results in this analysis was affected to a certain extent. The high-quality RCTs with large sample size, multi-blind, multi-centric are still required, and the methodological and normative clinical study protocol should be established and executed in the future.
Topics: Humans; Guided Tissue Regeneration, Periodontal; Alveolar Bone Loss; Periodontitis; Tooth Loss; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 37454056
DOI: 10.1186/s12903-023-03186-6