Organ Repair Research Articles

MG53 protects against contrast-induced acute kidney injury by reducing cell membrane damage and apoptosis.

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 μg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.

Human organ repair centers: Fact or fiction?

Human organ repair centers: Fact or fiction?

Directly coaxial 3D bioprinting of large-scale vascularized tissue constructs

Three-dimensional (3D) bioprinting of soft large-scale tissues in vitro is still a big challenge due to two limitations, (i) the lack of an effective way to print fine nutrient delivery channels (NDCs) inside the cell-laden structures above the millimetre level; (ii) the need for a feasible strategy to vascularize NDCs. Here, a novel 3D bioprinting method is reported to directly print cell-laden structures with effectively vascularized NDCs. Bioinks with desired tissue cells and endothelial cells (ECs) are separately and simultaneously printed from the outside (mixed with GelMA) and inside (mixed with gelatin) of a coaxial nozzle. As a result, the printed large-scale tissue consists of sheath-core fibers. At the same time, when the core fibers are dissolved to generate channels, the ECs deposit and adhere to the channels automatically. With this method, 3D cell-laden, vascularized tissue constructs (⩾1 cm) with a long-term culture (⩾20 d) are firstly reported. Specifically, vascularized cancer tissue constructs and osteogenic tissue constructs were generated. Considering the above advantages, this advanced bioprinting strategy has significant potential for building large-scale vascularized tissue constructs for applications in tissue engineering, and possibly even in regenerative medicine and organ repair.

Mesenchymal and Induced Pluripotent Stem Cells-Derived Extracellular Vesicles: The New Frontier for Regenerative Medicine?

Regenerative medicine aims to repair damaged, tissues or organs for the treatment of various diseases, which have been poorly managed with conventional drugs and medical procedures. To date, multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self-healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects, especially for mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) in damaged tissue restore are not dependent on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release extracellular vesicles (EVs). EVs play a fundamental role in cell-to-cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms through which MSCs and iPSCs-derived EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

MRNA and protein of p33ING1 in normal and cancer tissues.

BackgroundInhibitor growth protein 1 (ING1) is a tumor suppressor, and its down-regulation is involved in the progression and aggressive phenotypes of human malignancies through its interactions with the H3K4me3 and p53.MethodsWe collected datasets to analyze the relationship between ING1b mRNA expression and accumulative survival rate, and carried out immunohistochemistry analyses to determine the expression profiles of the p33ING1 protein on the mouse, normal human, and human cancer tissue microarrays.ResultsCompared with normal tissues, the ING1b mRNA was highly expressed in various types of cancer tissues, including, colorectal, lung, and breast cancers, and was positively correlated with the overall survival rate of gastric cancer patients. In mouse tissues, the subcellular location of p33ING1 was frequently nuclear; however, it was occasionally cytoplasmic or nucleocytoplasmic. There was a positive detection in the neuron body, a part of glial cells, the glandular epithelium of the stomach, intestines, breast, hepatocytes, heart, skeletal muscle cells, the bronchial and alveolar epithelium, and nephric tubules. In human tissues, the p33ING1 protein, apart from its cytoplasmic distribution, was distributed in the nuclei of the tongue, esophagus, stomach, intestine, lung, trachea, skin, appendix, cervix, endometrium, ovary, and breast. p33ING1 immunoreactivity was strongly detected in the stomach, trachea, skin, cervix, and breast, while it was weak in the other tissues. The positive rate of p33ING1 was 41.0% in the tested cancer entities (489/1,194). In general, p33ING1 expression was restricted to only the cytoplasm for all cancers, whereas it was found in the nucleus of renal clear cells, ovarian and colorectal cancers. Among them, p33ING1 was expressed in more than half of squamous cell carcinomas derived from the esophagus and cervix, while it was rarely expressed in hepatocellular (21.0%) and renal clear cell carcinoma (19.4%).ConclusionsThe findings suggest that p33ING1 might be participated in the repair and regeneration of organs or tissues the repair and regeneration of organs or tissue, and the carcinogenesis of the highly proliferative epithelium.

Building functional vascular grafts from human pluripotent stem cells-derived endothelial cells

Background & Aim Stem cell therapy may transform the treatment of cardiovascular disease, with an anticipated impact rivalling the results of revascularization and device therapies. Human pluripotent stem cells are currently developed as sources of tissue-specific cells for organ repair and regeneration. In clinically relevant small and large animal studies, we sought to investigate the feasibility of human embryonic and induced pluripotent stem cell-derived endothelial cell (hESC-EC, hiPSC-EC) engraftments. Methods, Results & Conclusion To generate endothelial cells, human pluripotent stem cells were treated with endothelial growth factors and CD31+ cell population was isolated from differentiating cultures. We obtained highly expandable populations of hESC-EC and hiPSC-EC which expressed mature endothelial cell markers. We implanted cell-laden hydrogel Matrigel subcutaneously into athymic nude rats. We studied angiogenesis in a small animal imaging system equipped with a high-resolution SPECT/CT and PET/MRI to acquire whole-body images. At two weeks after axillary or inguinal implantation in rats, a robust increase in local perfusion was detected by radiolabeled albumin at the engraftment sites, suggesting the functional incorporation of human hPSC-EC into the host microvasculature. Histology confirmed survival, successful engraftment, and formation of capillary-like structures. In a canine model, hiPSC-EC-seeded onto decellularised vascular segments were functional as infrarenal aortic interposition grafts. As assessed by quantitative PCR during follow-up, the expression of human angiogenic factors was induced, suggesting that endothelial cells may undergo maturation in vivo. Similar to the rodent model, we showed retention of hiPSC-EC and dynamic remodelling of the vessel wall with good maintenance of vascular patency in dogs. Combination of pluripotent stem cell-derived endothelial cells and biomatrices may be a promising tissue engineering approach to repair ischemic tissues and induce the formation of blood vessel networks.

Water-Dependent Blending of Pectin Films: The Mechanics of Conjoined Biopolymers.

Biodegradable pectin polymers have been recommended for a variety of biomedical applications, ranging from the delivery of oral drugs to the repair of injured visceral organs. A promising approach to regulate pectin biostability is the blending of pectin films. To investigate the development of conjoined films, we examined the physical properties of high-methoxyl pectin polymer-polymer (homopolymer) interactions at the adhesive interface. Pectin polymers were tested in glass phase (10–13% w/w water content) and gel phase (38–41% w/w water content). The tensile strength of polymer-polymer adhesion was measured after variable development time and compressive force. Regardless of pretest parameters, the adhesive strength of two glass phase films was negligible. In contrast, adhesion testing of two gel phase films resulted in significant tensile adhesion strength (p < 0.01). Adhesion was also observed between glass phase and gel phase films—likely reflecting the diffusion of water from the gel phase to the glass phase films. In studies of the interaction between two gel phase films, the polymer-polymer adhesive strength increased linearly with increasing compressive force (range 10–80 N) (R2 = 0.956). In contrast, adhesive strength increased logarithmically with time (range 10–10,000 s) (R2 = 0.913); most of the adhesive strength was observed within minutes of contact. Fracture mechanics demonstrated that the adhesion of two gel phase films resulted in a conjoined film with distinctive physical properties including increased extensibility, decreased stiffness and a 30% increase in the work of cohesion relative to native polymers (p < 0.01). Scanning electron microscopy of the conjoined films demonstrated cross-grain adhesion at the interface between the adhesive homopolymers. These structural and functional data suggest that blended pectin films have emergent physical properties resulting from the cross-grain intermingling of interfacial pectin chains.

Micro- and nanoparticles-based immunoregulation of macrophages for tissue repair and regeneration

The importance of inflammatory tissue microenvironment on the repair and regeneration of tissues and organs has been well recognized. In particular, the phenotypes of macrophages can significantly influence on the processes of tissue repair and remodeling. Among the many types of biomaterials, the particles in the range from nanometers to submicron meters have been extensively studied and applied in tissue engineering and regenerative medicine. They can actively interact with cells in different levels, and show the ability to regulate the polarization of macrophages. In this review, the influence of physicochemical properties such as size, surface charge, chemical components and surface modification of micro-nanoparticles on the immune behavior of macrophages, including endocytosis and phenotype switch, shall be introduced. The important roles of nanoparticles-based immunoregulation of macrophages on the chronic skin wounds regeneration, myocardial repair, liver repair and bone regeneration are discussed.

MTOR Signaling at the Crossroad between Metazoan Regeneration and Human Diseases.

A major challenge in medical research resides in controlling the molecular processes of tissue regeneration, as organ and structure damage are central to several human diseases. A survey of the literature reveals that mTOR (mechanistic/mammalian target of rapamycin) is involved in a wide range of regeneration mechanisms in the animal kingdom. More particularly, cellular processes such as growth, proliferation, and differentiation are controlled by mTOR. In addition, autophagy, stem cell maintenance or the newly described intermediate quiescence state, Galert, imply upstream monitoring by the mTOR pathway. In this review, we report the role of mTOR signaling in reparative regenerations in different tissues and body parts (e.g., axon, skeletal muscle, liver, epithelia, appendages, kidney, and whole-body), and highlight how the mTOR kinase can be viewed as a therapeutic target to boost organ repair. Studies in this area have focused on modulating the mTOR pathway in various animal models to elucidate its contribution to regeneration. The diversity of metazoan species used to identify the implication of this pathway might then serve applied medicine (in better understanding what is required for efficient treatments in human diseases) but also evolutionary biology. Indeed, species-specific differences in mTOR modulation can contain the keys to appreciate why certain regeneration processes have been lost or conserved in the animal kingdom.

A method for translational rat ex vivo lung perfusion experimentation.

The application of ex vivo lung perfusion (EVLP) has significantly increased the successful clinical use of marginal donor lungs. While large animal EVLP models exist to test new strategies to improve organ repair, there is currently no rat EVLP model capable of maintaining long-term lung viability. Here, we describe a new rat EVLP model that addresses this need, while enabling the study of lung injury due to cold ischemic time (CIT). The technique involves perfusing and ventilating male Lewis rat donor lungs for 4 h before transplanting the left lung into a recipient rat and then evaluating lung function 2 h after reperfusion. To test injury within this model, lungs were divided into groups and exposed to different CITs (i.e., 20 min, 6 h, 12 h, 18 h and 24 h). Experiments involving the 24-h-CIT group were prematurely terminated due to the development of severe edema. For the other groups, no differences in the ratio of arterial oxygen partial pressure to fractional inspired oxygen ([Formula: see text]/[Formula: see text]) were observed during EVLP; however, lung compliance decreased over time in the 18-h group (P = 0.012) and the [Formula: see text]/[Formula: see text] of the blood from the left pulmonary vein 2 h after transplantation was lower compared with 20-min-CIT group (P = 0.0062). This new model maintained stable lung function during 4-h EVLP and after transplantation when exposed to up to 12 h of CIT.

Transient Existence of Circulating Mesenchymal Stem Cells in the Deep Veins in Humans Following Long Bone Intramedullary Reaming.

The biology of mesenchymal stem cells (MSCs) in humans is incompletely understood and a possible role of systemically circulating cells in health and autoimmune disease remains controversial. Physiological movement of bone marrow MSCs to sites of injury would support the rationale for intravenous administration for relocation to damaged organs. We hypothesized that biophysical skeletal trauma rather than molecular cues may explain reported MSC circulation phenomena. Deep-femoral vein (FV) and matched peripheral vein blood samples (PVBs) were collected from patients undergoing lower-limb orthopaedic procedures during surgery (tibia using conventional sequential reaming, n = 9, femur using reamer/irrigator/aspirator (RIA), n = 15). PVBs were also taken from early (n = 15) and established (n = 12) rheumatoid arthritis (RA) patients and healthy donors (n = 12). Colony-forming unit-fibroblasts (CFU-Fs) were found in 17/36 FVBs but only 7/74 PVBs (mostly from femoral RIA); highly proliferative clonogenic cells were not generated. Only one colony was found in control/RA samples (n = 28). The rare CFU-Fs’ MSC nature was confirmed by phenotypic: CD105+/CD73+/CD90+ and CD19−/CD31−/CD33−/CD34−/CD45−/CD61−, and molecular profiles with 39/80 genes (including osteo-, chondro-, adipo-genic and immaturity markers) similar across multiple MSC tissue controls, but not dermal fibroblasts. Analysis of FVB-MSCs suggested that their likely origin was bone marrow as only two differences were observed between FVB-MSCs and IC-BM-MSCs (ACVR2A, p = 0.032 and MSX1, p = 0.003). Stromal cells with the phenotype and molecular profile of MSCs were scarcely found in the circulation, supporting the hypothesis that their very rare presence is likely linked to biophysical micro-damage caused by skeletal trauma (here orthopaedic manipulation) rather than specific molecular cues to a circulatory pool of MSCs capable of repair of remote organs or tissues. These findings support the use of organ resident cells or MSCs placed in situ to repair tissues rather than systemic administration.

Comparative assessment of morphological mechanisms of maintaining structural liver homeostasis in the dynamics of exposure to coal-rock dust and sodium fluoride on the body

Introduction.The impact on the body of such factors of the production environment as coal-rock dust and fluorine compounds leads to certain shift s in strict indicators of homeostasis at the system level. Maintaining the relative constancy of the internal environment of the body is provided by the functional consistency of all organs and systems, the leading of which is the liver. Organ repair plays a crucial role in restoring the structure of genetic material and maintaining normal cell viability. When this mechanism is damaged, the compensatory capabilities of the organ are disrupted, homeostasis is disrupted at the cellular and organizational levels, and the development of the main pathological processes is noted.The aim of the studyis to compare the morphological mechanisms of maintaining structural homeostasis of the liver in the dynamics of the impact on the body of coal-rock dust and sodium fluoride.Materials and methods. Experimental studies were conducted on adult white male laboratory rats. Features of morphological mechanisms for maintaining structural homeostasis of the liver in the dynamics of exposure to coal-rock dust and sodium fluoride were studied on experimental models of pneumoconiosis and fluoride intoxication. For histological examination in experimental animals, liver sampling was performed after 1, 3, 6, 9, 12 weeks of the experiment.Results. The specificity of morphological changes in the liver depending on the harmful production factor was revealed. It is shown that chronic exposure to coal-rock dust and sodium fluoride is characterized by the development of similar morphological changes in the liver and its vessels from the predominance of the initial compensatory-adaptive to pronounced violations of the stromal and parenchymal components. Long-term inhalation of coal-rock dust at 1–3 weeks of seeding triggers adaptive mechanisms in the liver in the form of increased functional activity of cells, formation of double-core hepatocytes, activation of immunocompetent cells and endotheliocytes, ensuring the preservation of the parenchyma and the general morphostructure of the organ until the 12th week of the experiment. Exposure to sodium fluoride leads to early disruption of liver compensatory mechanisms and the development of dystrophic changes in the parenchyma with the formation of necrosis foci as early as the 6th week of the experiment.Conclusions. The study of mechanisms for compensating the liver structure in conditions of long-term exposure to coal-rock dust and sodium fluoride, as well as processes that indicate their failure, and the timing of their occurrence, is of theoretical and practical importance for developing recommendations for the timely prevention and correction of pathological conditions developing in employees of the aluminum and coal industry.The authors declare no conflict of interests.

Recent Advances on Magnetic Sensitive Hydrogels in Tissue Engineering.

Tissue engineering is a promising strategy for the repair and regeneration of damaged tissues or organs. Biomaterials are one of the most important components in tissue engineering. Recently, magnetic hydrogels, which are fabricated using iron oxide-based particles and different types of hydrogel matrices, are becoming more and more attractive in biomedical applications by taking advantage of their biocompatibility, controlled architectures, and smart response to magnetic field remotely. In this literature review, the aim is to summarize the current development of magnetically sensitive smart hydrogels in tissue engineering, which is of great importance but has not yet been comprehensively viewed.

Eye on China

The following topics are under this section: A general framework for predictive maintenance of manufacturing systems A remote-controlled smart platform for organ repair COVID-19 and its genetic relationship with other coronaviruses East meets West: cancer therapy using acupuncture and electrochemistry A triple-function bismuth oxochromate photocatalyst AI enables whole-slide imaging for diagnosis of nasal polyps

Magnetic fields and angiogenesis

This review belongs to a special issue on magnetic surgery (using magnetic field in surgery), which has developed rapidly in the last few years and showed a great potential to be applied in numerous areas. While magnetic surgery has multiple advantages in surgical processes, including but not limited to shorten surgical procedure and duration, reduce inflammation and bleeding, it also adds another exposure source of relatively strong magnetic field to the human bodies. Consequently, concerns were raised regarding the potential adverse effects of these magnets on our bodies. Moreover, people have increased opportunities to be exposed to various magnetic fields generated by magnetic resonance imaging in hospitals, household magnets, cell phones and power lines, therefore, it is essential to investigate the effects of magnetic fields on human bodies. This review focuses on the effects of magnetic fields on the growth of blood vessels, a process known as angiogenesis. Angiogenesis is involved in a variety of physiological and pathological processes including organ growth and repair, and therefore plays important roles not only in surgical related processes, such as postoperative recovery, but also in other processes such as development and tumor growth. Angiogenesis is regulated by a balance between pro- and anti-angiogenic signals, which is frequently altered in various malignant, inflammatory, ischemic, infectious, and immune disorders. Many studies have investigated the influence of magnetic field on angiogenesis in the last few decades. Here in this review, we summarize, analyze and compare magnetic field parameters, such as strength, gradient and frequency, experimental procedures, biological samples examined and the detailed experimental results. Although there is still no consensus on the effects at cellular level, which is largely caused by a lack of systematic research on different magnetic field parameters, it is interesting that we found the angiogenesis of tumor tissues can be inhibited by both static and dynamic magnetic fields at animal level. In contrast, long-term or high-intensity static magnetic field treatment of non-tumor tissue seems to be able to promote angiogenesis at animal level. Since the experimental evidences are still inadequate, more systematic investigations are needed to further examine this correlation in the future. We also discuss the effect of magnetic field combined with chemotherapy and other treatment methods on angiogenesis and summarize the potential mechanisms of magnetic field on angiogenesis. It has been shown that static magnetic fields can affect multiple aspects of the cell, such as gene expression, cell proliferation, antioxidant defense system, as well as calcium levels. People speculate that magnetic field may regulate angiogenesis by affecting multiple signal transduction pathways including the calcium signaling pathway. Meanwhile there are also studies showing that other molecules could be involved in this process, including ROS (reactive oxygen species, ROS), ERK and membrane-bound receptors. Moreover, the mechanism of the differential effects of magnetic fields on angiogenesis in tumor tissue and non-tumor tissue are still not clear. Although physiological and pathological angiogenesis share many commonalities, there are also multiple different regulation pathways between angiogenesis of tumor vs. non-tumor tissues, such as the dependency of VEGF. In-depth investigations are warranted to better understand the effects and underlying mechanisms of varying magnetic fields with different parameters on angiogenesis in normal and pathological conditions. This review will not only help people to further understand the biological effects of magnetic fields, provide experimental basis for the safe application of magnetic surgery technology, but also lay a foundation for other potential medical applications of magnetic fields in the future.

Integration of Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes with Hydroxyapatite-Embedded Hyaluronic Acid-Alginate Hydrogel for Bone Regeneration.

The treatment of bone defects has plagued clinicians. Exosomes, the naturally secreted nanovesicles by cells, exhibit great potential in bone defect regeneration to realize cell-free therapy. In this work, we successfully revealed that human umbilical cord mesenchymal stem cells-derived exosomes could effectively promote the proliferation, migration, and osteogenic differentiation of a murine calvariae preosteoblast cell line in vitro. Considering the long period of bone regeneration, to effectively exert the reparative effect of exosomes, we synthesized an injectable hydroxyapatite (HAP)-embedded in situ cross-linked hyaluronic acid-alginate (HA-ALG) hydrogel system to durably retain exosomes at the defect sites. Then, we combined the exosomes with the HAP-embedded in situ cross-linked HA-ALG hydrogel system to repair bone defects in rats in vivo. The results showed that the combination of exosomes and composite hydrogel could significantly enhance bone regeneration. Our experiment provides a new strategy for exosome-based therapy, which shows great potential in future tissue and organ repair.

Notch signaling and taxis mechanisms regulate early stage angiogenesis: A mathematical and computational model

During angiogenesis, new blood vessels sprout and grow from existing ones. This process plays a crucial role in organ development and repair, in wound healing and in numerous pathological processes such as cancer progression or diabetes. Here, we present a mathematical model of early stage angiogenesis that permits exploration of the relative importance of mechanical, chemical and cellular cues. Endothelial cells proliferate and move over an extracellular matrix by following external gradients of Vessel Endothelial Growth Factor, adhesion and stiffness, which are incorporated to a Cellular Potts model with a finite element description of elasticity. The dynamics of Notch signaling involving Delta-4 and Jagged-1 ligands determines tip cell selection and vessel branching. Through their production rates, competing Jagged-Notch and Delta-Notch dynamics determine the influence of lateral inhibition and lateral induction on the selection of cellular phenotypes, branching of blood vessels, anastomosis (fusion of blood vessels) and angiogenesis velocity. Anastomosis may be favored or impeded depending on the mechanical configuration of strain vectors in the ECM near tip cells. Numerical simulations demonstrate that increasing Jagged production results in pathological vasculatures with thinner and more abundant vessels, which can be compensated by augmenting the production of Delta ligands.

The Many Facets of Erythropoietin Physiologic and Metabolic Response.

In mammals, erythropoietin (EPO), produced in the kidney, is essential for bone marrow erythropoiesis, and hypoxia induction of EPO production provides for the important erythropoietic response to ischemic stress, such as during blood loss and at high altitude. Erythropoietin acts by binding to its cell surface receptor which is expressed at the highest level on erythroid progenitor cells to promote cell survival, proliferation, and differentiation in production of mature red blood cells. In addition to bone marrow erythropoiesis, EPO causes multi-tissue responses associated with erythropoietin receptor (EPOR) expression in non-erythroid cells such neural cells, endothelial cells, and skeletal muscle myoblasts. Animal and cell models of ischemic stress have been useful in elucidating the potential benefit of EPO affecting maintenance and repair of several non-hematopoietic organs including brain, heart and skeletal muscle. Metabolic and glucose homeostasis are affected by endogenous EPO and erythropoietin administration affect, in part via EPOR expression in white adipose tissue. In diet-induced obese mice, EPO is protective for white adipose tissue inflammation and gives rise to a gender specific response in weight control associated with white fat mass accumulation. Erythropoietin regulation of fat mass is masked in female mice due to estrogen production. EPOR is also expressed in bone marrow stromal cells (BMSC) and EPO administration in mice results in reduced bone independent of the increase in hematocrit. Concomitant reduction in bone marrow adipocytes and bone morphogenic protein suggests that high EPO inhibits adipogenesis and osteogenesis. These multi-tissue responses underscore the pleiotropic potential of the EPO response and may contribute to various physiological manifestations accompanying anemia or ischemic response and pharmacological uses of EPO.

Co-overexpression of VEGF and GDNF in adipose-derived stem cells optimizes therapeutic effect in neurogenic erectile dysfunction model.

ObjectivesTo evaluate the rapid repair potential of adipose‐derived stem cells (ADSCs) co‐overexpressing VEGF and GDNF on bilateral cavernous nerve injury (BCNI) in rat models. Progressive fibrosis of the penis that occurs shortly after BCNI is a key cause of clinical treatment difficulty of erectile dysfunction (ED). Traditional medications are ineffective for ED caused by BCNI. ADSCs have shown therapeutic effects in animal models, but disappointing in clinical treatment suggests that we should explore optimal treatment of it.Materials and methodsWe extracted ADSCs from rat epididymis. Lentiviral transfection was verified by western blot and immunofluorescence. Thirty‐six SD rats (10 weeks old) were randomly divided into six groups (n = 6 per group): sham surgery, and remaining five BCNI groups transplanted PBS or ADSCs which were genetically modified by vehicle, VEGF (ADSC‐V), GDNF (ADSC‐G), or VEGF&GDNF (ADSC‐G&V) around major pelvic ganglion (MPG). We investigated the therapeutic effects of BCNI rat model which is characterized by ED, penile tissue fibrosis and hypoxia, and lack of nitrogen nerves or vascular atrophy.ResultsErectile function was almost recovered after 2 weeks of transplantation of ADSC‐G&V, promoted cavernous nerve repair, prevented penile fibrosis and preserving the vascular endothelium, which was significant differences amongst ADSC‐V or ADSC‐G. Moreover, GM‐ADSCs were detected in MPG and penis, indicating that their participation in repair of target organs and transverse nerves.ConclusionsThese promising data indicate that ADSCs co‐overexpressed VEGF and GDNF‐induced synergistic effects, make it a potential tool for recovering of erectile function speedily after BCNI.

Preparing a novel magnesium-doped hyaluronan/polyethyleneimine nanoparticle to improve endothelial functionalisation.

Nowadays, tissue engineering vascularisation has become an important means of organ repair and treatment of major traumatic diseases. Vascular endothelial layer regeneration and endothelial functionalisation are prerequisites and important components of tissue engineering vascularisation. The present researches of endothelial functionalisation mainly focus on tissue engineering scaffold preparation and implant surface modification. Few studies have reported the interaction of endothelial functionalisation and scaled materials, especially the nanomaterials. Magnesium (Mg), as an essential cytotropic active element in the human body, should promote the growth of endothelial cells. However, the authors' previous work found that the Mg in the alloys had a defect of delayed endothelialisation, which may be attributed to the non-uniform scales of the degradation products from Mg alloys. To validate this hypothesis and fabricate a novel nanomaterial for tissue engineering vascularisation, the authors prepared Mg-doped hyaluronan (HA)/polyethyleneimine (PEI) nanoparticles for endothelial cells testing. Their data showed that the Mg-doped HA/PEI nanoparticle with small scales (diameter <150 nm) presented better ability on improving endothelial cells growth, functionalisation and nitric oxide release.