-
Stem Cell Research & Therapy Dec 2023Systemic sclerosis (SSc) and sclerodermatous graft-versus-host disease (Scl-GVHD)-characterized by similar developmental fibrosis, vascular abnormalities, and innate and... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) and sclerodermatous graft-versus-host disease (Scl-GVHD)-characterized by similar developmental fibrosis, vascular abnormalities, and innate and adaptive immune response, resulting in severe skin fibrosis at the late stage-are chronic autoimmune diseases of connective tissue. The significant immune system dysfunction, distinguishing autoimmune-related fibrosis from mere skin fibrosis, should be a particular focus of treating autoimmune-related fibrosis. Recent research shows that innovative mesenchymal stem cell (MSC)-based therapy, with the capacities of immune regulation, inflammation suppression, oxidation inhibition, and fibrosis restraint, shows great promise in overcoming the disease.
MAIN BODY
This review of recent studies aims to summarize the therapeutic effect and theoretical mechanisms of MSC-based therapy in treating autoimmune-related fibrotic skin diseases, SSc and Scl-GVHD, providing novel insights and references for further clinical applications. It is noteworthy that the efficacy of MSCs is not reliant on their migration into the skin. Working on the immune system, MSCs can inhibit the chemotaxis and infiltration of immune cells to the skin by down-regulating the expression of skin chemokines and chemokine receptors and reducing the inflammatory and pro-fibrotic mediators. Furthermore, to reduce levels of oxidative stress, MSCs may improve vascular abnormalities, and enhance the antioxidant defenses through inducible nitric oxide synthase, thioredoxin 1, as well as other mediators. The oxidative stress environment does not weaken MSCs and may even strengthen certain functions. Regarding fibrosis, MSCs primarily target the transforming growth factor-β signaling pathway to inhibit fibroblast activation. Here, miRNAs may play a critical role in ECM remodeling. Clinical studies have demonstrated the safety of these approaches, though outcomes have varied, possibly owing to the heterogeneity of MSCs, the disorders themselves, and other factors. Nevertheless, the research clearly reveals the immense potential of MSCs in treating autoimmune-related fibrotic skin diseases.
CONCLUSION
The application of MSCs presents a promising approach for treating autoimmune-related fibrotic skin diseases: SSc and Scl-GVHD. Therapies involving MSCs and MSC extracellular vesicles have been found to operate through three primary mechanisms: rebalancing the immune and inflammatory disorders, resisting oxidant stress, and inhibiting overactivated fibrosis (including fibroblast activation and ECM remodeling). However, the effectiveness of these interventions requires further validation through extensive clinical investigations, particularly randomized control trials and phase III/IV clinical trials. Additionally, the hypothetical mechanism underlying these therapies could be elucidated through further research.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Scleroderma, Systemic; Skin Diseases; Autoimmune Diseases; Fibrosis; Skin; Graft vs Host Disease; Mesenchymal Stem Cells
PubMed: 38111001
DOI: 10.1186/s13287-023-03543-w -
Aging Sep 2023Hepatocellular carcinoma (HCC) is the most common subtype, accounting for about 90% of all primary liver cancers. The liver is rich in a large number of immune cells,...
Hepatocellular carcinoma (HCC) is the most common subtype, accounting for about 90% of all primary liver cancers. The liver is rich in a large number of immune cells, thus forming a special immune microenvironment, which plays a key role in the occurrence and development of hepatocellular carcinoma. Nowadays, tumor immunotherapy has become one of the most promising cancer treatment methods. Immune checkpoint inhibitors (ICIs) combined with VEGF inhibitors are listed as first-line treatment options for advanced HCC. Therefore, the search for a potential biomarker to predict the response to immunotherapy in HCC patients is urgently needed. The G protein-coupled receptor 55 (), a lysophosphatidylinositol (LPI) receptor, has recently emerged as a potential new target for anti-tumor therapy. Previous studies have found that is highly expressed in breast cancer, pancreatic cancer, skin cancer and cholangiocarcinoma, and is involved in tumor proliferation and migration. However, the role and mechanism of in HCC has not been elucidated. Therefore, this article discusses the clinical significance of in HCC and its correlation with the immune response of HCC patients, so as to provide theoretical basis for improving the prognosis of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Tumor Microenvironment; Receptors, Cannabinoid
PubMed: 37688769
DOI: 10.18632/aging.205008 -
Clinical, Cosmetic and Investigational... 2023The skin is a vital organ as the body's largest barrier, but its function declines with aging. Therefore, research into effective regeneration treatments must continue... (Review)
Review
INTRODUCTION
The skin is a vital organ as the body's largest barrier, but its function declines with aging. Therefore, research into effective regeneration treatments must continue to advance. Stem cell transplantation, a cell-based therapy, has become a popular skin-aging treatment, although it comes with drawbacks like host immune reactions. Stem cell-derived cell-free therapies have emerged as an alternative, backed by promising preclinical findings. Stem cell secretomes and extracellular vesicles (EVs) are the key components in cell-free therapy from stem cells. However, comprehensive reviews on the mechanisms of such treatments for skin aging are still limited.
PURPOSE
This review discusses stem cell-derived cell-free therapy's potential mechanisms of action related to skin aging prevention by identifying specific molecular targets suitable for the interventions.
METHODS
A search identified 27 relevant in vitro studies on stem cell-derived cell-free therapy interventions in skin aging model cells without restricting publication years using PubMed, Scopus, and Google Scholar.
RESULTS
Stem cell-derived cell-free therapy can prevent skin aging through various mechanisms, such as (1) involvement of multiple regenerative pathways [NFkb, AP-1, MAPK, P-AKT, NRF2, SIRT-1]; (2) oxidative stress regulation [by reducing oxidants (HO-1, NQO1) and enhancing antioxidants (SOD1, CAT, GP, FRAP)]; (3) preventing ECM degradation [by increasing elastin, collagen, HA, TIMP, and reducing MMP]; (4) regulating cell activity [by reducing cell senescence (SA-β-gal), apoptosis, and cell cycle arrest (P53, P12, P16); and enhancing autophagy, cell migration, and cell proliferation (Ki67)] (5) Regulating the inflammatory pathway [by reducing IL-6, IL-1, TNF-⍺, and increasing TGF-β]. Several clinical trials have also revealed improvements in wrinkles, elasticity, hydration, pores, and pigmentation.
CONCLUSION
Stem cell-derived cell-free therapy is a potential novel treatment for skin aging by cell rejuvenation through various molecular mechanisms.
PubMed: 38021432
DOI: 10.2147/CCID.S434439 -
The Journal of Dermatological Treatment Dec 2023To achieve international expert consensus and give recommendations on best practices in hair transplantation surgery, focusing on pre- and post-transplantation care.
AIM
To achieve international expert consensus and give recommendations on best practices in hair transplantation surgery, focusing on pre- and post-transplantation care.
METHODS
A modified Delphi method was used to reach consensus. An international scientific committee developed an 81-statement questionnaire. A panel of 38 experts in hair transplantation from 17 countries across 4 continents assessed the questionnaire.
RESULTS
Two consensus rounds were carried out, with 59 out of 81 statements (73%) reaching consensus. Expert recommendations emphasize the correct selection of candidates for hair transplantation and the need for patients to have received adequate medical treatment for alopecia before transplant. Comorbidities should be assessed and considered while planning surgery, and an individualized plan for perioperative care should be drawn up before transplant. Certain medications associated with increased risk of bleeding should be withdrawn before surgery. Specific recommendations for post-transplantation care are given. After transplantation, patients should gradually resume their normal haircare regimen. Close follow-up should be carried out during the first year after transplant.
CONCLUSIONS
This study presents numerous consensus-based recommendations on general aspects of hair transplantation, including candidate selection, medical therapy prior to transplantation, anesthesia, and resuming haircare after transplantation.
Topics: Humans; Skin Transplantation; Alopecia; Consensus; Hair
PubMed: 37477225
DOI: 10.1080/09546634.2023.2232065 -
Chinese Medical Journal Sep 2023In the field of plastic and reconstructive surgery, the loss of organs or tissues caused by diseases or injuries has resulted in challenges, such as donor shortage and... (Review)
Review
In the field of plastic and reconstructive surgery, the loss of organs or tissues caused by diseases or injuries has resulted in challenges, such as donor shortage and immunosuppression. In recent years, with the development of regenerative medicine, the decellularization-recellularization strategy seems to be a promising and attractive method to resolve these difficulties. The decellularized extracellular matrix contains no cells and genetic materials, while retaining the complex ultrastructure, and it can be used as a scaffold for cell seeding and subsequent transplantation, thereby promoting the regeneration of diseased or damaged tissues and organs. This review provided an overview of decellularization-recellularization technique, and mainly concentrated on the application of decellularization-recellularization technique in the field of plastic and reconstructive surgery, including the remodeling of skin, nose, ears, face, and limbs. Finally, we proposed the challenges in and the direction of future development of decellularization-recellularization technique in plastic surgery.
Topics: Tissue Engineering; Tissue Scaffolds; Surgery, Plastic; Regenerative Medicine; Extracellular Matrix
PubMed: 36752783
DOI: 10.1097/CM9.0000000000002085 -
Journal of Translational Medicine Sep 2023Vascularized composite allotransplantation can improve quality of life and restore functionality. However, the complex tissue composition of vascularized composite... (Review)
Review
Vascularized composite allotransplantation can improve quality of life and restore functionality. However, the complex tissue composition of vascularized composite allografts (VCAs) presents unique clinical challenges that increase the likelihood of transplant rejection. Under prolonged static cold storage, highly damage-susceptible tissues such as muscle and nerve undergo irreversible degradation that may render allografts non-functional. Skin-containing VCA elicits an immunogenic response that increases the risk of recipient allograft rejection. The development of quantitative metrics to evaluate VCAs prior to and following transplantation are key to mitigating allograft rejection. Correspondingly, a broad range of bioanalytical methods have emerged to assess the progression of VCA rejection and characterize transplantation outcomes. To consolidate the current range of relevant technologies and expand on potential for development, methods to evaluate ex vivo VCA status are herein reviewed and comparatively assessed. The use of implantable physiological status monitoring biochips, non-invasive bioimpedance monitoring to assess edema, and deep learning algorithms to fuse disparate inputs to stratify VCAs are identified.
Topics: Composite Tissue Allografts; Quality of Life; Vascularized Composite Allotransplantation; Transplantation, Homologous; Algorithms
PubMed: 37684651
DOI: 10.1186/s12967-023-04379-x -
Biomedicines Sep 2023Human skin is particularly vulnerable to external damaging influences such as irradiation, extreme temperatures, chemical trauma, and certain systemic diseases, which... (Review)
Review
Human skin is particularly vulnerable to external damaging influences such as irradiation, extreme temperatures, chemical trauma, and certain systemic diseases, which reduce the skin's capacity for regeneration and restoration and can possibly lead to large-scale skin defects. To restore skin continuity in severe cases, surgical interventions such as the transplantation of autologous tissue are needed. Nevertheless, the coverage of larger skin defects caused by severe third-grade burns or extensive irradiation therapy is limited due to the depletion of uninjured autologous tissue. In such cases, many of the patient's epidermal cells can become available using biofabricated skin grafts, thereby restoring the skin's vital functions. Given the limited availability of autologous skin grafts for restoring integrity in large-scale defects, using bioprinted constructs as skin graft substitutes could offer an encouraging therapeutic alternative to conventional therapies for large-scale wounds, such as the transplantation of autologous tissue. Using layer-by-layer aggregation or volumetric bioprinting, inkjet bioprinting, laser-assisted bioprinting, or extrusion-based bioprinting, skin cells are deposited in a desired pattern. The resulting constructs may be used as skin graft substitutes to accelerate wound healing and reconstitute the physiological functions of the skin. In this review, we aimed to elucidate the current state of bioprinting within the context of skin tissue engineering and introduce and discuss different bioprinting techniques, possible approaches and materials, commonly used cell types, and strategies for graft vascularization for the production of bioprinted constructs for use as skin graft substitutes.
PubMed: 37893053
DOI: 10.3390/biomedicines11102678 -
Open Life Sciences 2024Atopic dermatitis (AD) is a relapsing inflammatory skin condition that has become a global health issue with complex etiology and mounting prevalence. The association of... (Review)
Review
Atopic dermatitis (AD) is a relapsing inflammatory skin condition that has become a global health issue with complex etiology and mounting prevalence. The association of AD with skin and gut microbiota has been revealed by virtue of the continuous development of sequencing technology and genomics analysis. Also, the gut-brain-skin axis and its mutual crosstalk mechanisms have been gradually verified. Accordingly, the microbiota-skin-gut axis also plays an important role in allergic skin inflammation. Herein, we reviewed the relationship between the microbiota-skin-gut axis and AD, explored the underlying signaling molecules and potential pathways, and focused on the potential mechanisms of probiotics, antimicrobial peptides (AMPs), coagulase-negative staphylococci transplantation, fecal microbiota transplantation, AMPs, and addition of essential fatty acids in alleviating AD, with the aim to provide a new perspective for targeting microbiota in the treatment of allergic skin inflammation.
PubMed: 38623584
DOI: 10.1515/biol-2022-0782 -
Cells Aug 2023Vaccines have been hailed as one of the most remarkable medical advancements in human history, and their potential for treating cancer by generating or expanding...
Vaccines have been hailed as one of the most remarkable medical advancements in human history, and their potential for treating cancer by generating or expanding anti-tumor T cells has garnered significant interest in recent years. However, the limited efficacy of therapeutic cancer vaccines in clinical trials can be partially attributed to the inadequacy of current preclinical mouse models in recapitulating the complexities of the human immune system. In this study, we developed two innovative humanized mouse models to assess the immunogenicity and therapeutic effectiveness of vaccines targeting human papillomavirus (HPV16) antigens and delivering tumor antigens to human CD141 dendritic cells (DCs). Both models were based on the transference of human peripheral blood mononuclear cells (PBMCs) into immunocompromised HLA-A*02-NSG mice (NSG-A2), where the use of fresh PBMCs boosted the engraftment of human cells up to 80%. The dynamics of immune cells in the PBMC-hu-NSG-A2 mice demonstrated that T cells constituted the vast majority of engrafted cells, which progressively expanded over time and retained their responsiveness to ex vivo stimulation. Using the PBMC-hu-NSG-A2 system, we generated a hyperplastic skin graft model expressing the HPV16-E7 oncogene. Remarkably, human cells populated the skin grafts, and upon vaccination with a DNA vaccine encoding an HPV16-E6/E7 protein, rapid rejection targeted to the E7-expressing skin was detected, underscoring the capacity of the model to mount a vaccine-specific response. To overcome the decline in DC numbers observed over time in PBMC-hu-NSG-A2 animals, we augmented the abundance of CD141 DCs, the specific targets of our tailored nanoemulsions (TNEs), by transferring additional autologous PBMCs pre-treated with the growth factor Flt3-L. The Flt3-L treatment bolstered CD141 DC numbers, leading to potent antigen-specific CD4 and CD8 T cell responses , which caused the regression of pre-established triple-negative breast cancer and melanoma tumors following CD141 DC-targeting TNE vaccination. Notably, using HLA-A*02-matching PBMCs for humanizing NSG-A2 mice resulted in a delayed onset of graft-versus-host disease and enhanced the efficacy of the TNE vaccination compared with the parental NSG strain. In conclusion, we successfully established two humanized mouse models that exhibited strong antigen-specific responses and demonstrated tumor regression following vaccination. These models serve as valuable platforms for assessing the efficacy of therapeutic cancer vaccines targeting HPV16-dysplastic skin and diverse tumor antigens specifically delivered to CD141 DCs.
Topics: Humans; Animals; Mice; Cancer Vaccines; Skin Transplantation; Leukocytes, Mononuclear; Hyperplasia; Melanoma; Antibodies; Disease Models, Animal; Antigens, Neoplasm; Dendritic Cells; HLA-A Antigens
PubMed: 37626903
DOI: 10.3390/cells12162094 -
Journal of Investigative Surgery : the... Dec 2023Perifascial areolar tissue (PAT) is an areolar layer over the muscle fascia. PAT has been shown to be resistant to ischemia and prone to survival even in ischemic... (Review)
Review
BACKGROUND
Perifascial areolar tissue (PAT) is an areolar layer over the muscle fascia. PAT has been shown to be resistant to ischemia and prone to survival even in ischemic conditions. PAT grafts provide a vascular tissue layer on necrotic bone and tendons where skin grafting is not possible. The effect of PAT grafting on burn reconstruction has not yet been reported. Thus, in this study, we aimed to present our experience and discuss the role of PAT grafting in extremity burn reconstruction.
METHODS
Between January 2019 and December 2020, 16 PAT grafting procedures were performed in 11 patients. All patients had second- or third-degree burns in the upper and lower extremities, with exposed bone or tendon. PAT grafts were harvested from the abdominal region and were used for the upper extremity in 7 patients and the lower extremity in 4 patients. Immediate skin grafting was performed during the same session.
RESULTS
The patients' mean age was 50.7 years; defect size, 3.3 × 3 cm; and follow-up time, 11.8 months. The survival rates of the PAT and skin grafts were 93.8% and 68.6%, respectively. Partial skin graft losses were encountered in 4 patients, and total skin graft loss was seen in 1 patient.
CONCLUSION
PAT grafting is an alternative method to the use of dermal substitutes and flap surgery in small-to-medium-sized defects with exposed bone and tendon in burn patients.
Topics: Humans; Middle Aged; Surgical Flaps; Skin Transplantation; Burns; Tendons; Lower Extremity; Treatment Outcome
PubMed: 37004999
DOI: 10.1080/08941939.2023.2192786