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Regenerative Therapy Dec 2023The physiological process of wound healing is dynamic, continuous, and intricate. Nowadays, full-thickness burn wounds are treated by autologous skin transplantation....
OBJECTIVE
The physiological process of wound healing is dynamic, continuous, and intricate. Nowadays, full-thickness burn wounds are treated by autologous skin transplantation. Unfortunately, when substantial burns develop, there are fewer donor sites accessible, making it difficult to satisfy the requirement for large-scale skin transplants and increasing the risk of patient mortality. This study investigated the possibility of using a newly created hypoimmunogenic epidermal cell sheet to heal skin wounds.
METHODS
Transfection with lentivirus was used to generate Keratinocytes (KCs) that overexpress Indoleamine 2,3-Dioxygenase (IDO). Western blotting and quantitative polymerase chain reaction were used to measure IDO levels. To evaluate the function of IDO keratinocytes, CCK-8 and Transwell assays were performed. In cell sheet induction media, KCs and Fibroblasts (FBs) were cultured to yield epidermal cell sheets. The full-thickness skin excisions of BALB/c mice were transplanted with epidermal cell sheets. To assess the tumorigenicity of IDO keratinocytes, BALB/c nude mouse xenograft models were also used. CD3 and CD31 immunofluorescence labeling of wound tissue on day 12 to identify T lymphocyte infiltration and capillary development. ELISA measurement of IL-1 and TNF-α concentrations.
RESULTS
IDO keratinocytes dramatically enhanced the expression levels of IDO mRNA and protein, as well as the amount of kynurenine in the conditioned media of IDO keratinocytes, compared to the Control and NC groups. CD8 T cell apoptosis was considerably greater in the IDO group than in the Control and NC groups. Nevertheless, the proliferation and migratory capabilities of IDO keratinocytes were not substantially different from those of the Control and NC groups. In vitro cultivation of the hypoimmunogenic epidermal cell sheet was effective. In vivo transplantation experiments demonstrated that IDO epidermal cell sheets can effectively promote wound healing without tumorigenicity, and IDO epidermal cell sheets may promote wound healing by decreasing the expression levels of inflammatory factors (TNF and IL-1) in wound tissue, decreasing CD3 T lymphocytes, and increasing infiltration and new capillaries in wound tissue.
CONCLUSION
In this study, we successfully constructed the hypoimmunogenic epidermal cell sheet and demonstrated that the hypoimmunogenic epidermal cell sheet could accelerate wound healing.
PubMed: 37534237
DOI: 10.1016/j.reth.2023.07.003 -
Frontiers in Cell and Developmental... 2024This review systematically describes the application of mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the... (Review)
Review
This review systematically describes the application of mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the diverse research approaches essential for understanding CTCL's intricate pathogenesis and evaluating potential treatments. The review categorizes various mouse models, including xenograft, syngeneic transplantation, and genetically engineered mouse models (GEMMs), emphasizing their contributions to understanding tumor-host interactions, gene functions, and studies on drug efficacy in CTCL. It acknowledges the limitations of these models, particularly in fully replicating human immune responses and early stages of CTCL. The review also highlights novel developments focusing on the potential of skin-targeted GEMMs in studying natural skin lymphoma progression and interactions with the immune system from onset. In conclusion, a balanced understanding of these models' strengths and weaknesses are essential for accelerating the deciphering of CTCL pathogenesis and developing treatment methods. The GEMMs engineered to target specifically skin-homing CD4 T cells can be the next top mouse models that pave the way for exploring the effects of CTCL-related genes.
PubMed: 38665428
DOI: 10.3389/fcell.2024.1372881 -
Open Veterinary Journal Oct 2023The recovery of auto skin graft is a dynamic and complex process that requires a suitable environment for vascularization as nutrition delivery to cells and donor skin...
BACKGROUND
The recovery of auto skin graft is a dynamic and complex process that requires a suitable environment for vascularization as nutrition delivery to cells and donor skin reception.
AIMS
This research aimed to determine the effect of Tilapia skin dressing on the recovery of auto skin graft treatment on domestic cats through subjective and objective observation.
METHODS
Six male Indonesian local cats aged 1-2 years old weighing 3-4 kg were separated into two groups. The surgical procedure was performed in a sterile and aseptic environment. The first surgery created wound defects on the forelimb area 2 × 2 cm in size to whole groups. The wounds were left for 4 days and then treated with the following treatments; Group I (G-I) was treated with Tilapia skin dressing, and Group II (G-II) was treated with moist dressing Sofra-tulle. The dressing of the two groups was replaced every 3 days and evaluated subjectively and objectively.
RESULTS
Subjective observation showed that skin was reddish (day 3), the bleeding test showed bleeding immediately occurred after incision, and pain response was observed on day 6 post-surgery on both treatment groups showed significantly differences with 95% confidence level ( < 0.05). Objective observation in the form of NaCl 0.9% absorption and medicine effect on auto skin graft did not show a significant difference between the two treatment groups ( > 0.05).
CONCLUSION
Auto skin graft treatment by moist dressing showed better healing, but Tilapia skin dressing can be an alternative choice during auto skin graft treatment.
Topics: Male; Cats; Animals; Skin Transplantation; Tilapia; Bandages; Wound Healing; Administration, Cutaneous
PubMed: 38027407
DOI: 10.5455/OVJ.2023.v13.i10.14 -
EClinicalMedicine Dec 2023Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1...
Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215).
BACKGROUND
Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC.
METHODS
In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768.
FINDINGS
From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1-15.1). Median OS was 13.7 months (95% CI 9.3-17.7). Median DoR was 8.1 months (95% CI 1.7-10.6). ORR was 20% (95% CI 5.7-43.7). DCR was 95% (95% CI 75.1-99.9). CBR was 60% (95% CI 36.1-80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3-4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of P and family and a low-abundance of and . The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders.
INTERPRETATION
FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population.
FUNDING
This study was supported by the National Natural Science Foundation of China (82102954 to Wensi Zhao) and the Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).
PubMed: 38024475
DOI: 10.1016/j.eclinm.2023.102315 -
Annals of Hematology Mar 2024The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial...
The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While various therapeutic strategies have been explored in case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation is considered the only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of the underlying UBA1 mutant clone outside the context of allogeneic HCT. Both patients received treatment with the hypomethylating agent azacitidine, and deep molecular remission triggered treatment de-escalation and even cessation with sustained molecular remission in one of them. Prospective studies are necessary to clarify which VEXAS patients will benefit most from hypomethylating therapy and to understand the variability in the response to different treatment strategies.
Topics: Humans; Antimetabolites, Antineoplastic; Prospective Studies; Myelodysplastic Syndromes; Azacitidine; Pathologic Complete Response; Skin Diseases, Genetic
PubMed: 38214707
DOI: 10.1007/s00277-023-05611-w -
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 -
Frontiers in Physiology 2023The purpose of this study is to review the research progress of negative pressure wound therapy (NPWT) for scar revision and discuss the prospects of its further study... (Review)
Review
The purpose of this study is to review the research progress of negative pressure wound therapy (NPWT) for scar revision and discuss the prospects of its further study and application. The domestic and foreign literatures on NPWT for scar revision were reviewed. The mechanism and application were summarized. NPWT improves microcirculation and lymphatic flow and stimulates the growth of granulation tissues in addition to draining secretions and necrotic tissue. As a significant clinical therapy in scar revision, NPWT reduces tension, fixes graft, and improves wound bed. In the field of scar revision, NPWT has been increasingly used as an innovative and constantly improving technology.
PubMed: 37900944
DOI: 10.3389/fphys.2023.1194051 -
Cells Mar 2024Skin scarring and fibrosis affect millions of people worldwide, representing a serious clinical problem causing physical and psychological challenges for patients. Stem... (Review)
Review
Skin scarring and fibrosis affect millions of people worldwide, representing a serious clinical problem causing physical and psychological challenges for patients. Stem cell therapy and regenerative surgery represent a new area of treatment focused on promoting the body's natural ability to repair damaged tissue. Adipose-derived stem cells (ASCs) represent an optimal choice for practical regenerative medicine due to their abundance, autologous tissue origin, non-immunogenicity, and ease of access with minimal morbidity for patients. This review of the literature explores the current body of evidence around the use of ASCs-based regenerative strategies for the treatment of scarring and skin fibrosis, exploring the different surgical approaches and their application in multiple fibrotic skin conditions. Human, animal, and in vitro studies demonstrate that ASCs present potentialities in modifying scar tissue and fibrosis by suppressing extracellular matrix (ECM) synthesis and promoting the degradation of their constituents. Through softening skin fibrosis, function and overall quality of life may be considerably enhanced in different patient cohorts presenting with scar-related symptoms. The use of stem cell therapies for skin scar repair and regeneration represents a paradigm shift, offering potential alternative therapeutic avenues for fibrosis, a condition that currently lacks a cure.
Topics: Animals; Humans; Cicatrix; Quality of Life; Adipocytes; Fibrosis; Skin Diseases; Stem Cell Transplantation
PubMed: 38474408
DOI: 10.3390/cells13050443 -
Journal of Functional Biomaterials Oct 2023Biological tissues from various anatomical sources have been utilized for tissue transplantation and have developed into an important source of extracellular scaffolding... (Review)
Review
Biological tissues from various anatomical sources have been utilized for tissue transplantation and have developed into an important source of extracellular scaffolding material for regenerative medicine applications. Tissue scaffolds ideally integrate with host tissue and provide a homeostatic environment for cellular infiltration, growth, differentiation, and tissue resolution. The human amniotic membrane is considered an important source of scaffolding material due to its 3D structural architecture and function and as a source of growth factors and cytokines. This tissue source has been widely studied and used in various areas of tissue repair including intraoral reconstruction, corneal repair, tendon repair, microvascular reconstruction, nerve procedures, burns, and chronic wound treatment. The production of amniotic membrane allografts has not been standardized, resulting in a wide array of amniotic membrane products, including single, dual, and tri-layered products, such as amnion, chorion, amnion-chorion, amnion-amnion, and amnion-chorion-amnion allografts. Since these allografts are not processed using the same methods, they do not necessarily produce the same clinical responses. The aim of this review is to highlight the properties of different human allograft membranes, present the different processing and preservation methods, and discuss their use in tissue engineering and regenerative applications.
PubMed: 37888195
DOI: 10.3390/jfb14100531 -
Phytomedicine : International Journal... Nov 2023Bifidobacterium as probiotics, play important roles in skin status, while the potential mechanisms interaction remains unknown. The study further explored the potential...
BACKGROUND
Bifidobacterium as probiotics, play important roles in skin status, while the potential mechanisms interaction remains unknown. The study further explored the potential mechanism of B. longum 68S in ameliorating skin barrier damage from the perspective of the gut-skin axis in aging mice.
METHODS
B. longum 68S supplied natural aging mouse model and fecal microbiota transplantation (FMT) experiment proves the key role of intestinal microbiota in B. longum 68S up-regulating the production of ceramide synthesis key enzyme (SPT1) and ceramide level and improving skin barrier damage. Moreover, B. longum 68S supplied SPT1 gene deletion mouse model to investigate the mechanism of B. longum 68S on improving skin barrier damage.
RESULTS
Transcriptome analysis and 16S rRNA high-throughput pyrosequencing demonstrated that aging mice exhibited skin barrier dysfunction and intestinal dysbiosis. Meanwhile, aging mice exhibited an up-regulation in the trans epidermal water loss (TEWL) and a down-regulation in the level of SPT1, ceramide and skin barrier-related proteins (Loricrin, Keratin 10 and Desmoglein 1). Similarity, the FMT from aging mice to normal mice and SPT1 gene deletion mice could rebuild skin barrier damage and B. longum 68S supplementation exerted a positive effect on it. Further, B. longum 68S-mediated SPT1-derived ceramide production prevented impaired ceramide synthesis-induced endoplasmic reticulum stress and apoptotic response, ultimately improving skin barrier damage in vitro.
CONCLUSION
Emerging anti-aging therapies are necessary given the poor safety profiles of current pharmaceutical drugs. B. longum 68S may be better alternatives, considering the association between the gut microbiota and healthy aging. The findings suggested that B. longum 68S-mediated gut-skin axis homeostasis, thereby exhibiting an anti-aging effect and facilitate a better understanding of the mechanisms governing the various beneficial effects of B. longum 68S.
Topics: Animals; Mice; Bifidobacterium longum; RNA, Ribosomal, 16S; Aging; Ceramides; Disease Models, Animal; Homeostasis
PubMed: 37678055
DOI: 10.1016/j.phymed.2023.155051