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International Journal of Molecular... Mar 2024Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful... (Review)
Review
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing, utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscore the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds.
Topics: Humans; Endothelial Cells; Quality of Life; Wound Healing; Pluripotent Stem Cells; Intercellular Signaling Peptides and Proteins; Cytokines; Mesenchymal Stem Cell Transplantation
PubMed: 38474251
DOI: 10.3390/ijms25053006 -
Journal of the American Veterinary... Jun 2024Platelet-rich plasma (PRP) and mesenchymal stromal or stem cells (MSCs) have been investigated as treatments for equine tendon and ligament injuries, but little... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Platelet-rich plasma (PRP) and mesenchymal stromal or stem cells (MSCs) have been investigated as treatments for equine tendon and ligament injuries, but little consensus exists on the efficacy of these treatments. The study sought to evaluate the efficacy of PRP and MSC treatments by systematic review and meta-analysis.
METHODS
A systematic review was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Inclusion criteria required an original, peer-reviewed study where horses were administered MSCs or PRP (or both), and a comparator group was described. Studies were assessed for risk of bias and study quality. Random effects meta-analysis with inverse variance weighting was used to calculate pooled estimates of the ORs for the primary outcomes of return to performance and reinjury.
RESULTS
The search criteria identified 764 unique studies, and 21 studies met the inclusion criteria for the systematic review. Seventeen studies were further assessed for the primary outcomes of return to performance and reinjury rate within a meta-analysis. Meta-analyses revealed no increase in the likelihood of a return to performance with any of the biologic treatments. However, MSCs and MSCs administered concurrently with PRP provide a reduced risk of reinjury.
CLINICAL RELEVANCE
The current study identified a decrease in reinjury rate in horses administered MSCs or a combination of MSCs and PRP for tendinopathy and desmopathy. However, results should be interpreted with consideration of the heterogeneity of findings, poor study quality, and high risk of bias in the majority of studies.
Topics: Animals; Horses; Platelet-Rich Plasma; Tendon Injuries; Ligaments; Horse Diseases; Mesenchymal Stem Cell Transplantation
PubMed: 38471305
DOI: 10.2460/javma.23.12.0723 -
PloS One 2024Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid... (Meta-Analysis)
Meta-Analysis
Modified Mesenchymal stem cell, platelet-rich plasma, and hyaluronic acid intervention in early stage osteoarthritis: A systematic review, meta-analysis, and meta-regression of arthroscopic-guided intra-articular approaches.
BACKGROUND
Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid (HA). This study aimed to assess the synergy of MSCs, PRP, and varying HA doses, and determine optimal MSC sources to treat early-stage OA in the perspective of Lysholm score, VAS Score, KSS score, and WOMAC score.
METHOD
Original articles from 2013 to 2023 were screened from four databases, focusing on clinical trials and randomized controlled trials. The Risk of Bias in Non-randomized Studies-of Interventions (ROB-2) tool evaluated bias, and a PICOS criteria table guided result construction. Revman 5.4 analyzed outcomes such as Lysholm score, VAS score, KSS, WOMAC score, cartilage volume, and defect size using MRI. This systematic review adhered to PRISMA guidelines.
RESULT
Nine studies met the final inclusion criteria. Meta-analysis revealed a significant improvement in Lysholm score (MD: 17.89; 95% CI: 16.01, 19.77; I2 = 0%, P = 0.56), a notable reduction in VAS score (MD: -2.62; 95% CI: -2.83, -2.41; I2 = 99%, P < 0.00001), elevated KSS (MD: 29.59; 95% CI: 27.66, 31.52; I2 = 95%, P < 0.0001), and reduced WOMAC score (MD: -12.38; 95% CI: -13.75, -11.01; I2 = 99%, P < 0.0001).
CONCLUSIONS
Arthroscopic guided high-dose subchondral application of primary cultured synovial MSCs in popliteal PRP media with HA effectively regenerates cartilage defects and improves clinical outcomes in early-stage osteoarthritis. Clarification of MSC sources and quantities enhances the understanding of this promising treatment modality.
Topics: Humans; Hyaluronic Acid; Viscosupplements; Osteoarthritis, Knee; Injections, Intra-Articular; Platelet-Rich Plasma; Treatment Outcome
PubMed: 38457479
DOI: 10.1371/journal.pone.0295876 -
Stem Cell Reviews and Reports May 2024Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to... (Meta-Analysis)
Meta-Analysis
Mesenchymal Stromal/Stem Cell Therapy Improves Salivary Flow Rate in Radiation-Induced Salivary Gland Hypofunction in Preclinical in vivo Models: A Systematic Review and Meta-Analysis.
BACKGROUND
Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies.
METHODS
PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO ( www.crd.ac.uk/prospero ), registration number CRD42021227336.
RESULTS
A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55-11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors.
CONCLUSION
In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting.
Topics: Mesenchymal Stem Cell Transplantation; Salivary Glands; Animals; Mesenchymal Stem Cells; Humans; Radiation Injuries; Xerostomia
PubMed: 38430363
DOI: 10.1007/s12015-024-10700-y -
BMC Oral Health Mar 2024Ensuring the quantity, quality, and efficacy of human dental mesenchymal stem cells (MSCs) has become an urgent problem as their applications increase. Growth factors...
BACKGROUND
Ensuring the quantity, quality, and efficacy of human dental mesenchymal stem cells (MSCs) has become an urgent problem as their applications increase. Growth factors (GFs) have low toxicity, good biocompatibility, and regulate stem cell survival and differentiation. They bind to specific receptors on target cells, initiating signal transduction and triggering biological functions. So far, relatively few studies have been conducted to summarize the effect of different GFs on the application of dental MSCs. We have reviewed the literature from the past decade to examine the effectiveness and mechanism of applying one or multiple GFs to human dental MSCs. Our review is based on the premise that a single dental MSC cannot fulfill all applications and that different dental MSCs react differently to GFs.
METHODS
A search for published articles was carried out using the Web of Science core collection and PubMed. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. This review considered studies from 2014 to 2023 that examined the effects of GFs on human dental MSCs. The final selection of articles was made on the 15th of July 2023.
RESULTS
Three thousand eight hundred sixty-seven pieces of literature were gathered for this systematic review initially, only 56 of them were selected based on their focus on the effects of GFs during the application of human dental MSCs. Out of the 56, 32 literature pieces were focused on a single growth factor while 24 were focused on multiple growth factors. This study shows that GFs can regulate human dental MSCs through a multi-way processing manner.
CONCLUSION
Multimodal treatment of GFs can effectively regulate human dental MSCs, ensuring stem cell quality, quantity, and curative effects.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Cell Differentiation; Mesenchymal Stem Cells; Intercellular Signaling Peptides and Proteins
PubMed: 38429689
DOI: 10.1186/s12903-024-04013-2 -
Stem Cell Reviews and Reports May 2024The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of mesenchymal stem... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of mesenchymal stem cells (MSCs) on mortality in patients with COVID-19.
METHODS
A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with MSCs, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs).
RESULTS
Seventeen RCTs (enrolling 1019 participants) met the inclusion criteria. MSCs showed significant effect on 28-day mortality (RR 0.76, 95% CI 0.62 to 0.93; P = 0.008). There was no statistically significant difference in 60-day mortality (RR 0.87, 95% CI 0.70 to 1.09; P = 0.22), and 90-day mortality (RR 0.91, 95% CI 0.72 to 1.15; P = 0.44) between the two groups.
CONCLUSIONS
MSCs significantly reduced 28-day mortality in patients with COVID-19. The long-term effect of MSCs on mortality require further study.
Topics: Humans; COVID-19; Mesenchymal Stem Cell Transplantation; Randomized Controlled Trials as Topic; SARS-CoV-2; Mesenchymal Stem Cells
PubMed: 38427315
DOI: 10.1007/s12015-024-10705-7 -
Future Oncology (London, England) Feb 2024Perivascular epithelioid cell neoplasms (PEComas) are rare mesenchymal lesions, with gynecological PEComas accounting for just over a quarter of cases. Limited reports...
Perivascular epithelioid cell neoplasms (PEComas) are rare mesenchymal lesions, with gynecological PEComas accounting for just over a quarter of cases. Limited reports exist on gynecological PEComa, primarily treated with surgery; adjuvant therapy is considered in high-risk cases. This systematic review aims to summarize the origin and clinical, pathological and molecular characteristics of uterine PEComa, focusing on treatment options for gynecological PEComa. A comprehensive PubMed review of gynecological PEComa reports was conducted. A detailed examination of the literature ensured a thorough understanding. Gynecological PEComa diagnosis relies on histology and immunology. Despite therapy controversies, surgery remains the mainstay. Adjuvant therapy efficacy in high-risk cases is uncertain. mTOR inhibitors are the first line; alternative treatments, including angiogenesis and aromatase inhibitors, should be considered.
Topics: Female; Humans; Combined Modality Therapy; Diagnosis, Differential; Gynecology; Perivascular Epithelioid Cell Neoplasms
PubMed: 38426361
DOI: 10.2217/fon-2023-0778 -
Journal of Clinical Orthopaedics and... Mar 2024Focal chondral defects are often treated with cartilage restoration procedures. Malalignment often accompanies chondral defects. High tibial osteotomy (HTO), classically... (Review)
Review
BACKGROUND
Focal chondral defects are often treated with cartilage restoration procedures. Malalignment often accompanies chondral defects. High tibial osteotomy (HTO), classically utilized to treat uni-compartmental knee osteoarthritis, corrects malalignment. HTO combined with cartilage restoration procedures can treat uni-compartmental osteoarthritis and focal chondral defects.
PURPOSE
To assess outcomes of combined HTO and cartilage restoration procedures and review prognostic factors that may assist in preoperative planning and patient counseling.
STUDY DESIGN
Systematic Review of published literature.
METHODS
A systematic review of PubMed and Scopus was performed following PRISMA guidelines. Thirty-four papers were included in qualitative considerations.
RESULTS
Thirty-four papers that reported the combined outcome of HTO and cartilage repair were included. Twenty of the 34 included papers reported prognostic factors that affected the success or failure of combined HTO and cartilage repair surgery for focal articular defect and uni-compartmental knee osteoarthritis. Cartilage repair techniques that were combined with HTO and included in this review are bone marrow stimulation, allograft transplantation, osteochondral autograft transplantation, autologous chondrocyte implantation, and mesenchymal stem cell implantation.
CONCLUSIONS
HTO with adjunctive cartilage repair procedures improve clinical outcome scores and restore alignment in patients with medial compartment osteoarthritis and isolated focal chondral defects. HTO with adjunctive cartilage procedures produces optimal results in younger, non-obese patients with focal chondral defects and varus malalignment, without significant lateral compartment and patellofemoral involvement.
PubMed: 38425335
DOI: 10.1016/j.jcot.2024.102360 -
European Journal of Obstetrics,... May 2024The rate of caesarean section (CS) is increasing worldwide. Defects in uterine healing have a major gynaecological and obstetric impact (uterine rupture, caesarean scar...
The rate of caesarean section (CS) is increasing worldwide. Defects in uterine healing have a major gynaecological and obstetric impact (uterine rupture, caesarean scar defect, caesarean scar pregnancy, placenta accreta spectrum). The complex process of cellular uterine healing after surgery, and specifically after CS, remains poorly understood in contrast to skin wound healing. This literature review on uterine wound healing was mainly based on histological observations, particularly after CS. The primary objective of the review was to examine the effects of CS on uterine tissue at the cellular level, based on histological observations. The secondary objectives were to describe the biomechanical characteristics and the therapies used to improve scar tissue after CS. This review was performed using PRISMA criteria, and PubMed was the data source. The study included all clinical and animal model studies with CS and histological analysis of the uterine scar area (macroscopic, microscopic, immunohistochemical and biomechanical). Twenty studies were included: 10 human and 10 animal models. In total, 533 female humans and 511 female animals were included. Review articles, meeting abstracts, case series, case reports, and abstracts without access to full-text were excluded. The search was limited to studies published in English. No correlation was found between cutaneous and uterine healing. The histology of uterine scars is characterized by disorganized smooth muscle, fibrosis with collagen fibres and fewer endometrial glands. As for skin healing, the initial inflammation phase and mediation of some growth factors (particularly connective tissue growth factor, vascular endothelial growth factor, platelet-derived growth factor, tumour necrosis factor α and tumour necrosis factor β) seem to be essential. This initial phase has an impact on the subsequent phases of proliferation and maturation. Collagen appears to play a key role in the initial granulation tissue to replace the loss of substance. Subsequent maturation of the scar tissue is essential, with a decrease in collagen and smooth muscle restoration. Unlike skin, the glandular structure of uterine tissue could be responsible for the relatively high incidence of healing defects. Uterine scar defects after CS are characterized by an atrophic disorganized endometrium with atypia and a fibroblastic highly collagenic stromal reaction. Concerning immunohistochemistry, one study found a decrease in tumour necrosis factor β in uterine scar defects. No correlation was found between biomechanical characteristics (particularly uterine strength) and the presence of a collagenous scar after CS. Based on the findings of this review, an illustration of current understanding about uterine healing is provided. There is currently no validated prevention of caesarean scar defects. Various treatments to improve uterine healing after CS have been tested, and appeared to have good efficacy in animal studies: alpha lipoic acid, growth factors, collagen scaffolds and mesenchymal stem cells. Further prospective studies are needed.
Topics: Animals; Female; Humans; Pregnancy; Cesarean Section; Cicatrix; Collagen; Lymphotoxin-alpha; Uterine Diseases; Vascular Endothelial Growth Factor A; Wound Healing
PubMed: 38417279
DOI: 10.1016/j.ejogrb.2024.02.045 -
Stem Cell Reviews and Reports May 2024The aim of the study is to determine the effectiveness of stem cells in scaffolds in the treatment of bone deficits, in regard of bone regeneration, safety,... (Review)
Review
The aim of the study is to determine the effectiveness of stem cells in scaffolds in the treatment of bone deficits, in regard of bone regeneration, safety, rehabilitation and quality of life in humans. The systematic review was conducted in accordance with PRISMA 2020. A systematic search was conducted in three search engines and two registries lastly in 29-9-2022.for studies of the last 15 years. The risk of bias was assessed with RoB-2, ROBINS- I and NIH Quality of Before-After (Pre-Post) Studies with no Control group. The certainty of the results was assessed with the GRADE assessment tool. Due to heterogeneity, the results were reported in tables, graphs and narratively. The study protocol was published in PROSPERO with registration number CRD42022359049. Of the 10,091 studies retrieved, 14 were meeting the inclusion criteria, and were qualitatively analyzed. 138 patients were treated with mesenchymal stem cells in scaffolds, showing bone healing in all cases, and even with better results than the standard care. The adverse events were mild in most cases and in accordance with the surgery received. When assessed, there was a rehabilitation of the deficit and a gain in quality of life was detected. Although the heterogeneity between the studies and the small number of patients, the administration of mesenchymal stem cells in scaffolds seems safe and effective in the regeneration of bone defects. These results pave the way for the conduction of more clinical trials, with greater number of participants, with more standardized procedures.
Topics: Humans; Bone Regeneration; Mesenchymal Stem Cells; Tissue Scaffolds; Mesenchymal Stem Cell Transplantation; Quality of Life; Clinical Trials as Topic
PubMed: 38407793
DOI: 10.1007/s12015-024-10696-5