Transplantation Site Research Articles

Rebuilding microbiomes: Facilitating animal-microbe interactions through ecological restoration and rewilding.

Restoring degraded ecosystems is a complex process that involves rebuilding myriad species interactions that make a functioning ecological community. Microorganisms are key to robust ecological restoration - their mutualisms with above-ground communities drive community assembly and increase host fitness. However, microbes are largely ignored during restoration and there is a significant knowledge gap regarding how to restore their interactions with above-ground communities. Here, we tested whether we could enhance interactions between microbes and their invertebrate hosts by reintroducing, or 'rewilding', leaf litter and soil from remnant sites containing species-rich microbial communities, into species poor and geographically isolated revegetated farmland sites. We sequenced both the soil microbiome and the gut microbiome of two dominant invertebrates: native Ecnolagria grandis beetles and introduced Ommatoiulus moreleti millipedes. We sampled 35 months after the initial reintroduction event in remnant (conservation area and source of litter and soil transplant), rewilding transplant (revegetation site with transplant), and control sites (revegetation with no transplant). We found that even ∼20 years after revegetation, restoration sites had distinct microbial communities compared to remnant areas. Although litter and soil transplants failed to increase soil microbial community similarity towards remnant sites, we found marked increases in the diversity and richness of E. grandis microbiomes and a greater degree of overlap with soil microbiomes within rewilding transplant sites relative to control sites. In contrast, there were few changes in O. moreleti microbiomes. Overall, our results suggest rewilding can recover some species interactions during restoration but may not influence all host-microbe systems.

Effects of Restoration Through Nature-Based Solution on Benthic Biodiversity: A Case Study in a Northern Adriatic Lagoon

In the Caleri lagoon, a coastal lagoon in the Po River Delta, Northern Adriatic, the transplant of the dwarf eelgrass Zostera noltei was used as a nature-based solution to attempt the ecological restoration of a previously depleted lagoon area. A total of 135 15-cm-diameter sods were transplanted, with the donor site at the Venice lagoon. Using unmanned aerial vehicles (UAVs), eelgrass transplants were mapped and monitored with great precision. After two years, the area covered by eelgrass increased from the initial 2.5 m2 to 60 m2. Changes in the community structure and on the frequency of biological traits of macrobenthos occurred at the transplant site, with a higher frequency of epifaunal predators and herbivores, and of organisms with longer life spans and larger body sizes. Sensitive and indifferent taxa were always higher in the transplant site than in the bare bottom control site, where opportunistic taxa continued to dominate. Ecological quality status measured through M-AMBI and HBFI indices showed a clear improvement in the transplant site. The rapid changes in benthos demonstrate that even relatively small-scale transplantation of dwarf eelgrass can restore faunal communities very rapidly.

Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical optimization

Islet transplantation and more recently stem cell-derived islets were shown to successfully re-establish glycemic control in people with type 1 diabetes under immunosuppression. These results were achieved through intraportal infusion which leads to early graft losses and limits the capacity to contain and retrieve implanted cells in case of adverse events. Extra-hepatic sites and encapsulation devices have been developed to address these challenges and potentially create an immunoprotective or immune-privileged environment. Many strategies have achieved reversal of hyperglycemia in diabetic rodents. So far, the results have been less promising when transitioning to humans and larger animal models due to challenges in oxygenation and insulin delivery. We propose a versatile in vitro perfusion system to culture and experimentally study the function of centimeter-scale tissues and devices for insulin-secreting cell delivery. The system accommodates various tissue geometries, experimental readouts, and oxygenation tensions reflective of potential transplantation sites. We highlight the system’s applications by using case studies to explore three prominent bioartificial endocrine pancreas (BAP) configurations: (I) with internal flow, (II) with internal flow and microvascularized, and (III) without internal flow. Oxygen concentration profiles modeled computationally were analogous to viability gradients observed experimentally through live/dead endpoint measurements and in case I, time-lapse fluorescence imaging was used to monitor the viability of GFP-expressing cells in real time. Intervascular BAPs were cultured under flow for up to 3 days and BAPs without internal flow for up to 7 days, showing glucose-responsive insulin secretion quantified through at-line non-disruptive sampling. This system can complement other preclinical platforms to de-risk and optimize BAPs and other artificial tissue designs prior to clinical studies.

Obstruction Hernia Post Renal Transplant a Case Report in a Tertiary Care Center, Jeddah

<p><strong>Background: </strong>Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD) due to its superior outcomes compared to dialysis. However, complications such as infection, wound dehiscence, incisional hernia (IH), and rarely, renal paratransplant hernia (RPH) can occur post-transplant. This study reported a case of a patient with a post-renal transplant who presented abdominal symptoms requiring urgent laparotomy for an obstructed hernia at the transplant site.<br /><strong>Case Presentation: </strong>A 57-year-old male with non-alcoholic fatty liver disease, ESRD secondary to IgA nephropathy, myelofibrosis, and renal stones underwent a renal transplant from his son. He presented to the emergency department 6 days after he was discharged with severe abdominal pain, vomiting, and a visible bulge at the transplant incision. Ultrasound confirmed an IH with small bowel obstruction. Exploratory laparotomy successfully managed the hernia, and postoperative care included antibiotics and supportive measures. The patient recovered uneventfully and was discharged in good condition.<br /><strong>Conclusion:</strong> RPH represents a significant but uncommon complication following kidney transplantation. Timely identification and surgical intervention are essential for favorable outcomes. Despite the immunosuppressive risks, the incidence of RPH remains relatively low. Careful surgical planning is crucial to mitigate complications, and ongoing research is needed to refine treatment strategies, particularly exploring laparoscopic approaches in select cases.</p>

Experience in the use of testicular albuginea allogeneic material processing to change the phenotype of the gum

The work conducted a study of the phenotype of the gum after dental implantation surgery using testiqular albuginea allografts in comparison with dental implantation with apical displacement of the split mucous flap without the use of transimplants. The growth of keratized gum was assessed immediately after surgery and 6 months after surgical treatment. Morphological studies of biopsy tissue samples from the implant projection zone were conducted. The results of microscopic studies and photographing of samples are presented. Based on the obtained results, it was concluded that testicular albuginea allografts are completely replaced by a structurally complete connective tissue regenerate, but at the transplantation site, a phenotype of “thin” gum (thickness 1 mm or less) is formed, which, most likely, will not be able to provide adequate protection of the underlying tissues, which will contribute to plaque retention and subsequent inflammation.

Transplantation of Islet Organoids into Brown Adipose Tissue in a Diabetic Mouse Model.

Pancreatic islet transplantation is a promising cell replacement therapy for patients with type 1 diabetes (T1D), an autoimmune disease that destroys insulin-producing islet β cells. However, the shortage of donor pancreatic islets significantly limits the widespread use of this strategy as a routine therapy. Pluripotent stem cell-derived insulin-producing islet organoids present a promising alternative β cell source for T1D patients. One critical challenge is the lack of vascularization in islet organoids, making it essential to investigate vascularized transplantation sites to support their survival. Brown adipose tissue (BAT) is well vascularized and secretes active cytokines, facilitating islet organoid survival. Thus, BAT represents a promising transplantation site for islet organoids, making it an ideal location to support cell replacement therapies and improve treatment approaches for T1D. Here, we describe the methods for transplanting human-induced pluripotent stem cell (iPSC)-derived islet organoids into the BAT of a mouse model.

Long‐term response of Posidonia oceanica meadow restoration at the population and plant level: implications for management decisions

In recent years, numerous efforts to transplant Posidonia oceanica have been carried out in the Mediterranean Basin for experimental and large‐scale restoration purposes. However, data on the long‐term outcomes of these initiatives remain scarce. This study aims to address this gap by investigating the long‐term response of transplanted P. oceanica at both the population and plant level in comparison to adjacent natural meadows. We report on two large‐scale transplantation sites in Italy: Santa Marinella in the Central Tyrrhenian Sea and Ischia Porto in the Southern Tyrrhenian Sea, assessing their progress 14 and 10 years after transplantation, respectively. Descriptors of the meadows and of individual plants were investigated through field and laboratory activities. Sampling was conducted in both transplanted and adjacent control areas within the natural P. oceanica meadow. After about a decade, shoot density in the transplanted areas equaled that of the natural ones. Nevertheless, phenological and lepidochronological descriptors in the transplanted areas still did not match those of the natural meadows. Our work provides crucial information into the restoration process of P. oceanica, with implications for managing this habitat in line with recent EU marine legislation.

Physiological and symbiotic flexibility of reef‐building corals to new habitats: Insights from clonal colony transplants

Abstract Global decline of coral reefs shows varied responses to environmental stress, highlighting the need to understand these differences. The physiological plasticity of coral hosts and their microalgal symbionts can allow the coral holobiont to thrive in diverse marine environments, suggesting new strategies for effective restoration. To investigate local environmental influence on the physiology of two Caribbean coral species (Acropora palmata and Orbicella faveolata), clonal colonies from a land‐based nursery were transferred to nearshore and offshore reefs for one year. After transfer to coral reef habitats, both coral species shifted in photopigmentation and host energy reserves. Acropora palmata also shifted dominant symbionts and altered growth. Stable isotopes identified higher autotrophic proportions of metabolic carbon and higher photosynthesis rates in transplanted colonies compared to those in the land‐based nursery. Synthesis and applications. These findings improve our understanding of coral acclimatization and physiological plasticity, highlighting potential side effects of domestication. As coral restoration accelerates globally, this knowledge is crucial for guiding efforts and conserving endangered ecosystems by supplying considerations for improving coral‐rearing systems and providing information on genera‐specific acclimatization to transplant sites.

Nanoparticle contrast‐enhanced computed tomography and magnetic resonance imaging of vascularization of a subcutaneous niche for islet transplantation

AbstractRevascularization plays a critical role in the successful engraftment of transplanted pancreatic islets, which are inherently rich in capillaries to meet their high metabolic demands. Innovative islet encapsulation strategies such as the NICHE (neovascularized implantable cell homing and encapsulation), generate a prevascularized transplantation site that allows for direct integration of the graft with the systemic circulation. Timing the transplantation is key to maximizing islet engraftment and survival, especially in diabetic individuals, who exhibit impaired wound healing. Therefore, in this study, we explored different methods to assess vascular development within NICHE in vivo in a non‐invasive fashion. We effectively tracked neoangiogenesis using nanoparticle contrast‐enhanced computed tomography (nCECT), observing a steady increase in vascularization over an 8‐week period, which was confirmed histologically. Next, we estimated relative vascularization changes via T2 mapping with magnetic resonance imaging (MRI) before and after islet transplantation. On the first day post‐transplantation, we measured a slight decrease in T2 values followed by a significant increase by day 14 attributable to islet revascularization. Our findings underscore the potential of non‐invasive imaging techniques to provide insightful information on the readiness of the transplant site within cell encapsulation systems to support cell graft transplantation.

Fine-Scale Geographic Variation of Cladocopium in Acropora hyacinthus Across the Palauan Archipelago.

Symbiont genotype plays a vital role in the ability of a coral host to tolerate rising ocean temperatures, with some members of the family Symbiodiniaceae possessing more thermal tolerance than others. While existing studies on genetic structure in symbiont populations have focused on broader scales of 10-100 s of km, there is a noticeable gap in understanding the seascape genetics of coral symbionts at finer-yet ecologically and evolutionarily relevant-scales. Here, we mapped short reads from 271 holobiont genome libraries of individual Acropora hyacinthus colonies to protein coding genes from the chloroplast genome to identify patterns of symbiont population genetic structure. Utilizing this low-pass method, we assayed over 13,000 bases from every individual, enabling us to discern genetic variation at a finer geographic scale than previously reported at the population level. We identified five common Cladocopium chloroplast SNP profiles present across Palau, with symbiont structure varying between Northern, mid-lagoon, and Southern regions, and inshore-offshore gradients. Although symbiont populations within reefs typically contained significant genetic diversity, we also observed genetic structure between some nearby reefs. To explore whether coral hosts retain their symbionts post-transplantation, we experimentally moved 79 corals from their native reefs to transplant sites with both different and similar chloroplast SNP profiles. Over 12 months, we observed 12 instances where transplanted corals changed profiles, often transitioning to a profile present in adjacent corals. Symbiont genetic structure between reefs suggests either low dispersal of symbionts or environmental selection against dispersers, both resulting in the potential for significant adaptive differentiation across reef environments. The extent to which local corals and their symbionts are co-adapted to environments on a reef-by-reef scale is currently poorly known. Chloroplast sequences offer an additional tool for monitoring symbiont genetics and coral-symbiont interactions when assisted migration is used in restoration.

Cerium Oxide Nanoparticles-Reinforced GelMA Hydrogel Loading Bone Marrow Stem Cells with Osteogenic and Inflammatory Regulatory Capacity for Bone Defect Repair.

Effective bone defect repair has been a tough clinical challenge due to the complexity of the bone defect microenvironment. Hydrogels loaded with bone marrow mesenchymal stem cells (BMSCs) have been widely applied for bone regeneration. However, the low survival of BMSCs at the site of transplantation and lack of sufficient osteogenic induction capacity greatly limit their applications. In order to solve this puzzle, we fabricated gelatin methacryloyl (GelMA) hydrogels containing BMSCs with cerium oxide (CeO2) nanoparticles via photo-cross-linking to endow the composite hydrogel with osteogenic induction ability and immune induction ability. In vitro results demonstrated that the GelMA-CeO2-BMSC hydrogel presented with good biocompatibility and excellent osteogenic induction ability. In addition, the GelMA-CeO2-BMSC hydrogel could inhibit M1 polarization and promote M2 polarization, providing a good environment for the growth and osteogenic differentiation of BMSCs. Besides, the GelMA-CeO2-BMSC hydrogel was transplanted into critical-sized calvarial defects, and the results further confirmed its excellent bone regeneration capacity. In conclusion, the composite hydrogel provides a perspective for bone repair due to the remarkable potential for application in bone regeneration.

ECM Proteins Nidogen-1 and Decorin Restore Functionality of Human Islets of Langerhans upon Hypoxic Conditions.

Transplantation of donor islets of Langerhans is a potential therapeutic approach for patients with diabetes mellitus; however, its success is limited by islet death and dysfunction during the initial hypoxic conditions at the transplantation site. This highlights the need to support the donor islets in the days post-transplantation until the site is vascularized. It was previously demonstrated that the extracellular matrix (ECM) proteins nidogen-1 (NID1) and decorin (DCN) improve the functionality and survival of the β-cell line, EndoC-βH3, and the viability of human islets post-isolation. To advance the use of these ECM proteins toward a clinical application and elucidate the mechanisms of action in primary islets, the study assesses the effects of ECM proteins NID1 and DCN on isolated human donor islets cultured in normoxic and hypoxic conditions. NID1- and DCN-treatment restore β-cell functionality of human donor islets in a hypoxic environment through upregulation of genes involved in glycolytic pathways and reducing DNA fragmentation in hypoxic conditions comparable to normoxic control islets. The results demonstrate that the utilization of NID1 or DCN with islets of Langerhans may have the potential to overcome the hypoxia-induced cell death observed post-transplantation and improve transplant outcomes.

Mitochondria-Rich Microvesicles Alleviate CNI ED by Transferring Mitochondria and Suppressing Local Ferroptosis.

Erectile dysfunction (ED) frequently arises as a complication of pelvic surgeries, including rectal and prostate surgery, and has no definitive cure. This study explored whether mitochondria-rich microvesicles (MVs) can be used to treat ED stemming from cavernous nerve injury (CNI) and investigated its potential mechanisms. We isolated MVs and mitochondria (MT) from PC12. The apoptosis rate, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitochondrial derived reactive oxygen species (mtROS), iron content, malondialdehyde (MDA) content and endogenous antioxidant system activity of corpus cavernosum smooth muscle cells (CCSMCs) cultured with MVs and MT were detected in vitro. In vivo, twenty-four male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI group were injected with PBS, MVs and MT respectively. After fourteen days of treatment, the erectile function was measured and penile tissues were collected for histological analysis. Subsequently, inhibition of mitochondria in MV was performed to explore the mechanism of the rescue experiment. The CCSMCs, PC12-MVs and PC12-MT were successfully isolated and identified. After MVs culture, apoptosis rate, ROS, mtROS, iron content and MDA content of CCSMCs were significantly decreased, while MMP and the activities of endogenous antioxidant system were increased. MVs transplantation can significantly restore erectile function and smooth muscle content in CNIED rats. The rescue experiment suggested that MVs exerted the above therapeutic effect by transferring mitochondria within it. MVs transplantation significantly improve erectile function in CNI ED rats. MVs may play a role in anti-OS and anti-ferroptosis at the transplant site through efficient transfer of mitochondria, providing a potential treatment vehicle for CNI ED.

Survival and prognostic factors for relapsed childhood acute lymphoblastic leukemia after treatment with the Chinese children's cancer group ALL-2015 protocol: a single center results.

This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University. The study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS. As of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P < 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse. Despite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University.

Multisite Injections of Canine Glial-Restricted Progenitors Promote Brain Myelination and Extend the Survival of Dysmyelinated Mice

Glial cell dysfunction results in myelin loss and leads to subsequent motor and cognitive deficits throughout the demyelinating disease course.Therefore, in various therapeutic approaches, significant attention has been directed toward glial-restricted progenitor (GRP) transplantation for myelin repair and remyelination, and numerous studies using exogenous GRP injection in rodent models of hypomyelinating diseases have been performed. Previously, we proposed the transplantation of canine glial-restricted progenitors (cGRPs) into the double-mutant immunodeficient, demyelinated neonatal shiverer mice (shiverer/Rag2−/−). The results of our previous study revealed the myelination of axons within the corpus callosum of transplanted animals; however, the extent of myelination and lifespan prolongation depended on the transplantation site (anterior vs. posterior). The goal of our present study was to optimize the therapeutic effect of cGRP transplantation by using a multisite injection protocol to achieve a broader dispersal of donor cells in the host and obtain better therapeutic results. Experimental analysis of cGRP graft recipients revealed a marked elevation in myelin basic protein (MBP) expression and prominent axonal myelination across the brains of shiverer mice. Interestingly, the proportion of galactosyl ceramidase (GalC) positive cells was similar between the brains of cGRP recipients and control mice, implying a natural propensity of exogenous cGRPs to generate mature, myelinating oligodendrocytes. Moreover, multisite injection of cGRPs improved mice survival as compared to non-transplanted animals.

Enhancement of Subcutaneous Islet Transplant Performance by Collagen 1 Gel

Human islets can be transplanted into the portal vein for T1 diabetes, and a similar procedure is being used in a clinical trial for stem cell–derived beta-like cells. Efforts have been underway to find an alternative transplant site that will foster better islet cell survival and function. Although conceptually attractive, the subcutaneous (SC) site has yielded disappointing results, in spite of some improvements resulting from more attention paid to vascularization and differentiation factors, including collagen. We developed a method to transplant rat islets in a disk of type 1 collagen gel and found improved efficacy of these transplants. Survival of islets following transplantation (tx) was determined by comparing insulin content of the graft to that of the pre-transplant islets from the same isolation. At 14 days after transplantation, grafts of the disks had more than double the recovered insulin than islets transplanted in ungelled collagen. SC grafts of disks had similar insulin content to grafts in a kidney site and in epididymal fat pads. In vivo disks underwent contraction to 10% of initial volume within 24 h but the islets remained healthy and well distributed. Whole mount imaging showed that residual donor vascular cells within the islets expanded and connected to ingrowing host blood vessels. Islets (400 rat islet equivalents (IEQ)) in the collagen disks transplanted into an SC site of NOD scid IL2R gammanull (NSG) mice reversed streptozotocin (STZ)-induced diabetes within 10 days as effectively as transplants in the kidney site. Thus, a simple change of placing islets into a gel of collagen 1 prior to transplantation allowed a prompt reversal of STZ-induced diabetes using SC site.

443.2: Liver surface can be a promising transplant site for pancreatic islets using a gelatin hydrogel nonwoven fabric combined with ADSCs.

443.2: Liver surface can be a promising transplant site for pancreatic islets using a gelatin hydrogel nonwoven fabric combined with ADSCs.

Effect of AMH on primordial follicle populations in mouse ovaries and human pre-pubertal ovarian xenografts during doxorubicin treatment.

Survival rates of the childhood cancer patients are improving, however cancer treatments such as chemotherapy may lead to infertility due to loss of the primordial follicle (PMF) reserve. Doxorubicin (DXR) is a gonadotoxic chemotherapy agent commonly used in childhood cancers. Anti-Müllerian Hormone (AMH) has been reported to have a protective effect on the mouse ovarian reserve against DXR in vivo. However, whether AMH can prevent PMF loss in conjunction with DXR in human ovarian tissue in vivo has not been determined. In order to investigate this, we first established an optimum dose of DXR that induced PMF loss in cultured mouse ovaries and investigated the efficacy of AMH on reducing DXR-induced PMF loss in mice in vitro. Second, we investigated the effects of DXR on pre-pubertal human ovarian tissue and the ability of AMH to prevent DXR-induced damage comparing using a mouse xenograft model with different transplantation sites. Mouse ovaries treated with DXR in vitro and in vivo had reduced PMF populations and damaged follicle health. We did not observe effect of DXR-induced PMF loss or damage to follicle/stromal health in human ovarian cortex, this might have been due to an insufficient dose or duration of DXR. Although AMH does not prevent DXR-induced PMF loss in pre-pubertal and adult mouse ovaries, in mouse ovaries treated with higher concentration of AMH in vitro, DXR did not cause a significant loss in PMFs. This is the first study to illustrate an effect of AMH on DXR-induced PMF loss on pre-pubertal mouse ovaries. However, more experiments with higher doses of AMH and larger sample size are needed to confirm this finding. We did not observe that AMH could prevent DXR-induced PMF loss in mouse ovaries in vivo. Further studies are warranted to investigate whether AMH has a protective effect against DXR in xenotransplanted human ovarian tissue. Thus, to obtain robust evidence about the potential of AMH in fertility preservation during chemotherapy treatment, alternative AMH administration strategies need to be explored alongside DXR administration to fully interrogate the effect of DXR and AMH on human xenografted tissues.

Aspirin attenuates the detrimental effects of TNF-α on BMMSC stemness by modulating the YAP-SMAD7 axis

BackgroundBone marrow mesenchymal stem cells (BMMSCs) are commonly used for cell transplantation to treat refractory diseases. However, the presence of inflammatory factors, such as tumour necrosis factor-alpha (TNF-α), at the transplantation site severely compromises the stemness of BMMSCs, thereby reducing the therapeutic effect of cell transplantation. Aspirin (AS) is a drug that has been in use for over a century and has a wide range of effects, including the regulation of cell proliferation, multidirectional differentiation, and immunomodulatory properties of stem cells. However, it is still unclear whether AS can delay the damaging effects of TNF-α on BMMSC stemness.MethodsThis study investigated the effects of AS and TNF-α on BMMSC stemness and the molecular mechanisms using colony formation assay, western blot, qRT-PCR, and overexpression or knockdown of YAP and SMAD7.ResultsThe results demonstrated that TNF-α inhibited cell proliferation, the expression of stemness, osteogenic and chondrogenic differentiation markers of BMMSCs. Treatment with AS was shown to mitigate the TNF-α-induced damage to BMMSC stemness. Mechanistic studies revealed that AS may reverse the damage caused by TNF-α on BMMSC stemness by upregulating YAP and inhibiting the expression of SMAD7.ConclusionAS can attenuate the damaging effects of TNF-α on BMMSC stemness by regulating the YAP-SMAD7 axis. These findings are expected to promote the application of AS to improve the efficacy of stem cell therapy.

Impact of oxygen and glucose availability on the viability and connectivity of islet cells: A computational study of reconstructed avascular human islets.

The experimental study and transplantation of pancreatic islets requires their isolation from the surrounding tissue, and therefore, from the vasculature. Under these conditions, avascular islets rely on the diffusion of peripheral oxygen and nutrients to comply with the requirements of islet cells while responding to changes in body glucose. As a complement to the experimental work, computational models have been widely used to estimate how avascular islets would be affected by the hypoxic conditions found both in culture and transplant sites. However, previous models have been based on simplified representations of pancreatic islets which has limited the reach of the simulations performed. Aiming to contribute with a more realistic model of avascular human islets, in this work we used architectures of human islets reconstructed from experimental data to simulate the availability of oxygen for α, β and δ-cells, emulating culture and transplant conditions at different glucose concentrations. The modeling approach proposed allowed us to quantitatively estimate how the loss of cells due to severe hypoxia would impact interactions between islet cells, ultimately segregating the islet into disconnected subnetworks. According to the simulations performed, islet encapsulation, by reducing the oxygen available within the islets, could severely compromise cell viability. Moreover, our model suggests that even without encapsulation, only microislets composed of less than 100 cells would remain viable in oxygenation conditions found in transplant sites. Overall, in this article we delineate a novel modeling methodology to simulate detailed avascular islets in experimental and transplant conditions with potential applications in the field of islet encapsulation.