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Nature Communications Jun 2024The longevity of grafts remains a major challenge in allogeneic transplantation due to immune rejection. Systemic immunosuppression can impair graft function and can...
The longevity of grafts remains a major challenge in allogeneic transplantation due to immune rejection. Systemic immunosuppression can impair graft function and can also cause severe adverse effects. Here, we report a local immuno-protective strategy to enhance post-transplant persistence of allografts using a mesenchymal stem cell membrane-derived vesicle (MMV)-crosslinked hydrogel (MMV-Gel). MMVs are engineered to upregulate expression of Fas ligand (FasL) and programmed death ligand 1 (PD-L1). The MMVs are retained within the hydrogel by crosslinking. The immuno-protective microenvironment of the hydrogel protects allografts by presenting FasL and PD-L1. The binding of these ligands to T effector cells, the dominant contributors to graft destruction and rejection, results in apoptosis of T effector cells and generation of regulatory T cells. We demonstrate that implantation with MMV-Gel prolongs the survival and function of grafts in mouse models of allogeneic pancreatic islet cells and skin transplantation.
Topics: Animals; Hydrogels; Mice; Fas Ligand Protein; Transplantation, Homologous; Mice, Inbred C57BL; T-Lymphocytes, Regulatory; Islets of Langerhans Transplantation; Skin Transplantation; B7-H1 Antigen; Mesenchymal Stem Cells; Mice, Inbred BALB C; Graft Survival; Graft Rejection; Humans; Male; Apoptosis
PubMed: 38890279
DOI: 10.1038/s41467-024-49135-x -
Clinical Case Reports Jun 2024The immunomodulatory effect of CMV makes coinfection with other microbes, like VZV possible and potentially deadlier in the post kidney transplant period. Treatment...
KEY CLINICAL MESSAGE
The immunomodulatory effect of CMV makes coinfection with other microbes, like VZV possible and potentially deadlier in the post kidney transplant period. Treatment should be started promptly. Both infections can be treated with Valganciclovir.
ABSTRACT
Infections are common complications in kidney transplant recipients owing to the lifelong immunosuppression. Cytomegalovirus (CMV) and Varicella Zoster Virus (VZV) infections are quite common in the posttransplant period. Coinfection with both however has been reported only once. The immunomodulatory effect of CMV makes their interaction with other organisms like VZV potentially sinister. This is a case of a young woman who developed coinfection with HZV and CMV in the first month following a live related kidney transplantation from her mother. Transplant surgery went well with good urine output, but serum creatinine did not fall below 1.7 mg/dL. Immunosuppression consisted of intravenous (IV), followed by oral prednisolone, Mycophenolate Sodium (MPS) and Tacrolimus. 25 days after an uneventful surgery, she developed fever, followed by pain and vesicular eruption on the forehead, typical of VZV infection, along with rising creatinine. CMV PCR yielded 300 copies/mL of DNA, which was undetectable in both donor and recipient pre-transplant. Total white blood cell count fell to 2 × 10/L. MPS was temporarily stopped. Treatment with Valgancyclovir led to resolution of fever, skin lesions and brought serum creatinine down to baseline over 2 weeks.
PubMed: 38887304
DOI: 10.1002/ccr3.9089 -
Microsurgery Jul 2024One of the biggest challenges with gender-affirming vaginoplasty was the creation of a long-lasting, durable, patent, and self-lubricating neovaginal canal that allowed...
INTRODUCTION
One of the biggest challenges with gender-affirming vaginoplasty was the creation of a long-lasting, durable, patent, and self-lubricating neovaginal canal that allowed for spontaneous, pain-free sexual intercourse. The jejunum was a durable, physiologic, and intestinal option to create the neovaginal canal that minimizes the adverse effects of skin graft, peritoneal, and colonic vaginoplasties. Free jejunal vaginoplasties had been performed in cis females for congenital genitourinary anomalies like Mullerian agenesis or after gynecologic-oncologic surgery but had yet to be reported for gender-affirming vaginoplasties. The purpose of this report was to present a technique for a physiologic, intestinal, gender-affirming vaginoplasty without the disadvantages of colonic vaginoplasties.
PATIENTS AND METHODS
This report presented six patients, all natal males who identified as female, undergoing robotic-assisted free jejunal flap gender-affirming vaginoplasty. Mean age was 35.8 years (range: 21-66). Mean body mass index was 33.2 kg/m (range: 28.0-41.0). The proximal aspect of the neovaginal canal was created intra-abdominally by elevating peritoneal flaps from the posterior bladder wall to be reflected downward into the external neovaginal canal. The jejunal flap was harvested. The greater saphenous vein was harvested to create an arteriovenous loop between the flap vessels and the recipient femoral artery in an end-to-side fashion and a branch of the femoral vein. The jejunal flap was passed intra-abdominally through the groin incision and then trans-peritoneally into the neovaginal canal. The jejunal segment was inset to the proximal peritoneal flaps and the distal inverted penoscrotal skin of the neovaginal introitus.
RESULTS
Mean length of the harvest jejunal segment was 19.2 cm (range: 15-20). Mean time to ambulation, foley removal, and first vaginal dilation were 3.3 (range: 3-4), 4.0 (range: 3-5), and 4.5 days (range: 4-6), respectively. By a mean follow-up duration of 8.0 months (range: 1-14), mean vaginal depth and diameter were 7.0 and 1.3 cm (range: 1.0-1.5), respectively. Two (33.3%) patients experienced postoperative complications, including groin hematoma (n = 1, 16.7%) and reoperation for correction of dehiscence of the jejunal flap to the vaginal introitus (n = 1, 16.7%).
CONCLUSION
Gender-affirming surgeons should consider a free vascularized segment of jejunum as an option to line the neovaginal canal in the correct patients.
Topics: Humans; Female; Vagina; Male; Jejunum; Free Tissue Flaps; Adult; Robotic Surgical Procedures; Sex Reassignment Surgery; Middle Aged; Aged; Young Adult; Plastic Surgery Procedures; Treatment Outcome; Retrospective Studies; Surgically-Created Structures
PubMed: 38887138
DOI: 10.1002/micr.31202 -
Microsurgery Jul 2024The scapular free flap (SFF) is essential in complex reconstructive surgery and often indicated in complex defects with compromised or poor local tissue integrity. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The scapular free flap (SFF) is essential in complex reconstructive surgery and often indicated in complex defects with compromised or poor local tissue integrity. This review aims to assess the versatility and reliability of the SFF during reconstruction.
METHODS
A comprehensive literature review of multiple databases was conducted following the PRISMA guidelines. An analysis of pooled data was performed to evaluate flap failure rate for any anatomical unit using SFF as the primary endpoints. Secondary endpoints included other complication rates after reconstruction such as partial flap loss, revision surgery, fistula, hematoma, and infection.
RESULTS
A total of 110 articles were included, with 1447 pooled flaps. The main recipient site was the head and neck region (89.0%). Major indications for reconstruction were malignancy (55.3%), burns (19.2%), and trauma (9.3%). The most common types of flaps were osteocutaneous (23.3%), cutaneous (22.6%), and chimeric (18.0%). The pooled flap failure rate was 2% (95%CI: 1%-4%). No significant heterogeneity was present across studies (Q statistic 20.2, p = .69; I .00%, p = .685). Nonscapular supplementary flaps and grafts were required in 61 cases. The average length and surface area of bone flaps were 7.2 cm and 24.8cm, respectively. The average skin paddle area was 134.2cm.
CONCLUSION
The SFF is a useful adjunct in the reconstructive surgeon's armamentarium as evidence by its intrinsic versatility and diverse clinical indications. Our data suggest a low failure rate in multicomponent defect reconstruction, especially in head and neck surgery. SFFs enable incorporation of multiple tissue types and customizable dimensions-both for vascularized bone and cutaneous skin-augmenting its value in the microsurgeon's repertoire as a chimeric flap. Further research is necessary to overcome the conventional barriers to SFF utilization and to better comprehend the specific scenarios in which the SFF can serve as the preferred alternative workhorse flap.
Topics: Humans; Free Tissue Flaps; Scapula; Plastic Surgery Procedures; Graft Survival; Postoperative Complications
PubMed: 38887104
DOI: 10.1002/micr.31203 -
ACS Applied Bio Materials Jun 2024Human tissue kallikrein-related peptidase 7 (KLK7) is a serine protease implicated in the physiology of skin desquamation, and its uncontrolled activity can lead to...
Human tissue kallikrein-related peptidase 7 (KLK7) is a serine protease implicated in the physiology of skin desquamation, and its uncontrolled activity can lead to chronic diseases such as psoriasis, atopic dermatitis, and Netherton syndrome. For this reason, kallikrein 7 has been identified as a potential therapeutic target. This work aimed to evaluate Pluronic (PL) hydrogels as topical carriers of four specific scFv-Fc antibodies to inhibit KLK7. The hydrogels comprised PL F127 (30% w/v) alone and a binary F127/P123 (28-2% w/v) system. Each formulation was loaded with 1 μg/mL of each antibody and characterized by physicochemical and pharmaceutical techniques, considering antibody-micelle interactions and hydrogel behavior as smart delivery systems. Results showed that the antibodies were successfully loaded into the PL-based systems, and the sol-gel transition temperature was shifted to high values after the P123 addition. The antibodies released from the gels preserved their rheological properties (' > '', 35- to 41-fold) and inhibitory activity against KLK7, even after 24 h. This work presented potential agents targeting KLK7 that may provide strategies for treating skin abnormalities.
PubMed: 38886921
DOI: 10.1021/acsabm.4c00371 -
Stem Cell Research & Therapy Jun 2024The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as...
AIMS AND OBJECTIVES
The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study.
METHOD
Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events.
RESULTS
In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte-keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP.
CONCLUSION
Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study.
Topics: Adult; Female; Humans; Male; Platelet-Rich Plasma; Randomized Controlled Trials as Topic; Regenerative Medicine; Skin Diseases
PubMed: 38886861
DOI: 10.1186/s13287-024-03800-6 -
Stem Cell Research & Therapy Jun 2024Fibrosis is a pathological process, that could result in permanent scarring and impairment of the physiological function of the affected organ; this condition which is... (Review)
Review
Fibrosis is a pathological process, that could result in permanent scarring and impairment of the physiological function of the affected organ; this condition which is categorized under the term organ failure could affect various organs in different situations. The involvement of the major organs, such as the lungs, liver, kidney, heart, and skin, is associated with a high rate of morbidity and mortality across the world. Fibrotic disorders encompass a broad range of complications and could be traced to various illnesses and impairments; these could range from simple skin scars with beauty issues to severe rheumatologic or inflammatory disorders such as systemic sclerosis as well as idiopathic pulmonary fibrosis. Besides, the overactivation of immune responses during any inflammatory condition causing tissue damage could contribute to the pathogenic fibrotic events accompanying the healing response; for instance, the inflammation resulting from tissue engraftment could cause the formation of fibrotic scars in the grafted tissue, even in cases where the immune system deals with hard to clear infections, fibrotic scars could follow and cause severe adverse effects. A good example of such a complication is post-Covid19 lung fibrosis which could impair the life of the affected individuals with extensive lung involvement. However, effective therapies that halt or slow down the progression of fibrosis are missing in the current clinical settings. Considering the immunomodulatory and regenerative potential of distinct stem cell types, their application as an anti-fibrotic agent, capable of attenuating tissue fibrosis has been investigated by many researchers. Although the majority of the studies addressing the anti-fibrotic effects of stem cells indicated their potent capabilities, the underlying mechanisms, and pathways by which these cells could impact fibrotic processes remain poorly understood. Here, we first, review the properties of various stem cell types utilized so far as anti-fibrotic treatments and discuss the challenges and limitations associated with their applications in clinical settings; then, we will summarize the general and organ-specific mechanisms and pathways contributing to tissue fibrosis; finally, we will describe the mechanisms and pathways considered to be employed by distinct stem cell types for exerting anti-fibrotic events.
Topics: Humans; Fibrosis; Stem Cell Transplantation; Scleroderma, Systemic; Animals; COVID-19
PubMed: 38886859
DOI: 10.1186/s13287-024-03782-5 -
Stem Cell Research & Therapy Jun 2024With the development of the economy and the increasing prevalence of skin problems, cutaneous medical aesthetics are gaining more and more attention. Skin disorders like... (Review)
Review
With the development of the economy and the increasing prevalence of skin problems, cutaneous medical aesthetics are gaining more and more attention. Skin disorders like poor wound healing, aging, and pigmentation have an impact not only on appearance but also on patients with physical and psychological issues, and even impose a significant financial burden on families and society. However, due to the complexities of its occurrence, present treatment options cannot produce optimal outcomes, indicating a dire need for new and effective treatments. Mesenchymal stem cells (MSCs) and their secretomics treatment is a new regenerative medicine therapy that promotes and regulates endogenous stem cell populations and/or replenishes cell pools to achieve tissue homeostasis and regeneration. It has demonstrated remarkable advantages in several skin-related in vivo and in vitro investigations, aiding in the improvement of skin conditions and the promotion of skin aesthetics. As a result, this review gives a complete description of recent scientific breakthroughs in MSCs for skin aesthetics and the limitations of their clinical applications, aiming to provide new ideas for future research and clinical transformation.
Topics: Humans; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Skin; Regenerative Medicine; Skin Diseases; Wound Healing; Animals
PubMed: 38886773
DOI: 10.1186/s13287-024-03774-5 -
BMC Cardiovascular Disorders Jun 2024Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome,...
BACKGROUND
Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation.
CASE PRESENTATION
Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation.
CONCLUSIONS
Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.
Topics: Humans; Cardiomyopathy, Dilated; Male; Carney Complex; Adult; Heart Transplantation; Myxoma; Heart Failure; Heart Neoplasms; Treatment Outcome; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
PubMed: 38886700
DOI: 10.1186/s12872-024-03946-4 -
Blood Advances Jun 2024Cutaneous sclerosis, a highly morbid subtype of chronic graft vs. host disease (cGVHD), demonstrates limited treatment response under current NIH Response Measures. We...
Cutaneous sclerosis, a highly morbid subtype of chronic graft vs. host disease (cGVHD), demonstrates limited treatment response under current NIH Response Measures. We explored novel sclerosis-specific response measures using Chronic GVHD Consortium data. A training cohort included patients with cutaneous sclerosis from a randomized trial of imatinib vs. rituximab, and a Consortium observational study. The validation cohort was a different Consortium observational study. Clinician-reported measures (baseline, and baseline to 6-month change) were examined for association with 6-month clinician-reported response. Patient-reported measures (baseline and baseline to 6-month change) were studied for association with 6-month patient-reported response. A total of 347 subjects were included (training 183, validation 164). While multiple skin and joint measures were associated with clinician-reported response on univariate analysis, PROM total score, PROM total score change, and NIH 0-3 skin change were retained in the final multivariate model (AUC 0.83 training, 0.75 validation). Similarly, many patient-reported measures were associated, but final multivariate analysis retained the HAP AAS, SF36 vitality change, LSS skin, and LSS skin change in the model (AUC 0.86 training, 0.75 validation). We identified which sclerosis measures have greatest association with 6-month clinician- and patient-reported treatment response, a previously unstudied area. However, given the observed performance in the validation cohorts, we conclude that further work is needed. Novel response measures may be needed to optimally assess treatment response in cutaneous sclerosis.
PubMed: 38885484
DOI: 10.1182/bloodadvances.2024013233