Organ Repair Research Articles

Recent trends in stem cell-based therapies and applications of artificial intelligence in regenerative medicine.

Stem cells are undifferentiated cells that can self-renew and differentiate into diverse types of mature and functional cells while maintaining their original identity. This profound potential of stem cells has been thoroughly investigated for its significance in regenerative medicine and has laid the foundation for cell-based therapies. Regenerative medicine is rapidly progressing in healthcare with the prospect of repair and restoration of specific organs or tissue injuries or chronic disease conditions where the body’s regenerative process is not sufficient to heal. In this review, the recent advances in stem cell-based therapies in regenerative medicine are discussed, emphasizing mesenchymal stem cell-based therapies as these cells have been extensively studied for clinical use. Recent applications of artificial intelligence algorithms in stem cell-based therapies, their limitation, and future prospects are highlighted.

Applications of 3D Bio-Printing in Tissue Engineering and Biomedicine.

In recent years, 3D bio-printing technology has developed rapidly and become an advanced bio-manufacturing technology. At present, 3D bio-printing technology has been explored in the fields of tissue engineering, drug testing and screening, regenerative medicine and clinical disease research and has achieved many research results. Among them, the application of 3D bio-printing technology in tissue engineering has been widely concerned by researchers, and it contributing many breakthroughs in the preparation of tissue engineering scaffolds. In the future, it is possible to print fully functional tissues or organs by using 3D bio-printing technology which exhibiting great potential development prospects in th applications of organ transplantation and human body implants. It is expected to solve thebiomedical problems of organ shortage and repair of damaged tissues and organs. Besides,3Dbio-printing technology will benefit human beings in more fields. Therefore, this paper reviews the current applications, research progresses and limitations of 3D bio-printing technology in biomedical and life sciences, and discusses the main printing strategies of 3D bio-printing technology. And, the research emphases, possible development trends and suggestions of the application of 3D bio-printing are summarized to provide references for the application research of 3D bio-printing.

Extracellular Vesicles for the Treatment of Radiation Injuries.

Normal tissue injury from accidental or therapeutic exposure to high-dose radiation can cause severe acute and delayed toxicities, which result in mortality and chronic morbidity. Exposure to single high-dose radiation leads to a multi-organ failure, known as acute radiation syndrome, which is caused by radiation-induced oxidative stress and DNA damage to tissue stem cells. The radiation exposure results in acute cell loss, cell cycle arrest, senescence, and early damage to bone marrow and intestine with high mortality from sepsis. There is an urgent need for developing medical countermeasures against radiation injury for normal tissue toxicity. In this review, we discuss the potential of applying secretory extracellular vesicles derived from mesenchymal stromal/stem cells, endothelial cells, and macrophages for promoting repair and regeneration of organs after radiation injury.

Relentless Regeneration

Regenerative Medicine is a branch of medicine holding promise for the repair of cells, tissues, and organs to effective function. Much of the field has been developed in response to damage sustained by injury and disease. However, the body is under constant maintenance with a natural ebb and flow of dying and renewing cells. In addition, cells, tissues, and organs are constantly responding to routine demands to accommodate great variations in signals and responses. Remarkable examples are the cells composing the blood vessels and airways of the lungs. The ability to regulate, maintain and respond to changes in blood pressure and gas exchange across the blood-air interface illustrates the relentless ability of our bodies to self-adjust and self-renew throughout life. Likewise, the earth in which we live is under constant change and remodeling. Natural disasters such as volcanic eruptions and earthquakes, with time, recover and become incorporated into the rhythm of daily life. Initial recovery may be brutal but in both cases, the body and the earth have an amazing power to heal.

δ-MnO2 changed the structure of humic-like acid during co-composting of chicken manure and rice straw

Improving the structure and quantity of humus is important to reduce agriculture organic waste by composting. The present study was aimed to assess the role of δ-MnO2 on humus fractions formation during co-composting of chicken manure and rice straw. Two tests (control group (CK), the addition of δ-MnO2 (M)) were carried out. The results showed that organic matter content decreased by 34% and 29% at M and CK, suggesting the process of organic waste disposal was accelerated by adding δ-MnO2. The structures and quantity of fulvic acid (FA) and humic acid (HA) (as the main fractions of humus) were investigated. The δ-MnO2 had no significant effect on improving the concentration of FA and HA (p>0.05). However, the addition of δ-MnO2 caused different effects on the FA and HA structure. The humification degree of FA improved, while bioavailability of HA increased through adding δ-MnO2. The addition of δ-MnO2 rephased the bacterial community structure, slowing down the succession rate of the bacterial community in M composting. After adding δ-MnO2, the structural equation modeling results showed that environmental factors could directly drive changes in FA and HA by modulating the bacterial community. Furthermore, the role of FA and HA in the soil amendment was also demonstrated. Therefore, the addition of MnO2 might be promising for agriculture organic waste treatment and environmental repair during composting.

Obesity in Angiogenesis and Regenerative Lung Growth after Pneumonectomy

Obese population is rapidly growing worldwide. Obesity is associated with impairment of wound healing and tissue regeneration. Angiogenesis, the formation of new blood capillaries, plays a key role in organ regeneration and repair. We and other groups have reported that inhibition of angiogenesis attenuates lung growth after unilateral pneumonectomy (PNX) and that obesity is accompanied by endothelial cell dysfunction. However, the effects of obesity on lung regeneration remain unclear. Compensatory lung growth and vascular and alveolar morphogenesis after PNX are suppressed in leptin-deficient ob/ob mice treated with high-fat diet compared to that in control lean mice. The levels of the major angiogenic factor, vascular endothelial growth factor (VEGF) are higher in the serum and the lung tissue collected from post-PNX mice compared to those from sham-operated control mice, while these effects are attenuated in post-PNX leptin-deficient ob/ob mice with high-fat diet. Among various VEGF isoforms, VEGF164, but not VEGF188 and VEGF120, increases in the post-PNX mouse lungs, while these effects are inhibited in obese mice. These results suggestthat obesity inhibits post-PNX regenerative lung growth through VEGF164 signaling. Modulation of VEGF signaling may be the efficient strategy to restore lung regeneration and repair in obese people.

Hydrogels as Emerging Materials for Cornea Wound Healing.

Hydrogel biomaterials have many favorable characteristics including tuneable mechanical behavior, cytocompatibility, optical properties suitable for regeneration and restoration of the damaged cornea tissue. The cornea is a tissue susceptible to various injuries and traumas with a complicated healing cascade, in which conserving its transparency and integrity is critical. Accordingly, the hydrogels' known properties along with the stimulation of nerve and cell regeneration make them ideal scaffold for corneal tissue engineering. Hydrogels have been used extensively in clinical applications for the repair and replacement of diseased organs. The development and optimizing of novel hydrogels to repair/replace corneal injuries have been the main focus of researches within the last decade. This research aims to critically review in vitro, preclinical, as well as clinical trial studies related to corneal wound healing using hydrogels in the past 10 years, as this is considered as an emerging technology for corneal treatment. Several unique modifications of hydrogels with smart behaviors have undergone early phase clinical trials and showed promising outcomes. Financially, this considers a multibillion dollars industry and with huge interest from medical devices as well as pharmaceutical industries with several products may emerge within the next five years.

Graphene Oxide: Opportunities and Challenges in Biomedicine.

Desirable carbon allotropes such as graphene oxide (GO) have entered the field with several biomedical applications, owing to their exceptional physicochemical and biological features, including extreme strength, found to be 200 times stronger than steel; remarkable light weight; large surface-to-volume ratio; chemical stability; unparalleled thermal and electrical conductivity; and enhanced cell adhesion, proliferation, and differentiation properties. The presence of functional groups on graphene oxide (GO) enhances further interactions with other molecules. Therefore, recent studies have focused on GO-based materials (GOBMs) rather than graphene. The aim of this research was to highlight the physicochemical and biological properties of GOBMs, especially their significance to biomedical applications. The latest studies of GOBMs in biomedical applications are critically reviewed, and in vitro and preclinical studies are assessed. Furthermore, the challenges likely to be faced and prospective future potential are addressed. GOBMs, a high potential emerging material, will dominate the materials of choice in the repair and development of human organs and medical devices. There is already great interest among academics as well as in pharmaceutical and biomedical industries.

Treatment of Stress Urinary Incontinence with Muscle Stem Cells and Stem Cell Components: Chances, Challenges and Future Prospects.

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges.

Effect of lung boost device on inspiratory muscle strength in abdominal surgery patients

Background: Abdominal surgery involves a surgical repair, resection or reconstruction of organs inside the abdominal cavity. This may include surgery on the stomach, gallbladder, small intestine (colon), liver, pancreas, spleen, esophagus and appendix affected by infection, obstruction, cancerous growth or inflammatory bowel disease. Post Pulmonary Complications (PPCs), are defined as pulmonary anomalies taking place in the postoperative period producing clinically notable, identifiable disease or dysfunction that critically affects the clinical course. As deconditioning is one of the most common and unnecessary causes of morbidity and mortality, the interventions that are implemented should have the potential to increase the strength of the respiratory muscles and accordingly, expand exercise performance and functional capacity as indicated. The aim of the study was to determine the effect of lung boost device on inspiratory muscle strength training in abdominal surgery patients. Material and Methods: Thirty participants between the age of 20 to 70 years that underwent abdominal surgery were selected and received inspiratory muscle training by lung boost device for twice daily 6 times in a week for 2 weeks. Pre and post intervention assessments were done by PIMax and 6MWD. Result: Result of this study showed significant difference in the PIMax and 6MWD when treated with Lung Boost device. Conclusion: The study concluded that use of Lung Boost device causes significant improvement in inspiratory muscle strength and 6MWD in group of abdominal surgery patients and so addition of Lung Boost device in patients with abdominal surgery will increase the strength of inspiratory muscle as well as the functional capacity. KEY WORDS: Abdominal surgery, Lung Boost device, Maximal inspiratory pressure (PIMax), 6Minute Walk Distance (6MWD).

Prenatal Development and Function of Human Mononuclear Phagocytes.

The human mononuclear phagocyte (MP) system, which includes dendritic cells, monocytes, and macrophages, is a critical regulator of innate and adaptive immune responses. During embryonic development, MPs derive sequentially in yolk sac progenitors, fetal liver, and bone marrow haematopoietic stem cells. MPs maintain tissue homeostasis and confer protective immunity in post-natal life. Recent evidence – primarily in animal models – highlight their critical role in coordinating the remodeling, maturation, and repair of target organs during embryonic and fetal development. However, the molecular regulation governing chemotaxis, homeostasis, and functional diversification of resident MP cells in their respective organ systems during development remains elusive. In this review, we summarize the current understanding of the development and functional contribution of tissue MPs during human organ development and morphogenesis and its relevance to regenerative medicine. We outline how single-cell multi-omic approaches and next-generation ex-vivo organ-on-chip models provide new experimental platforms to study the role of human MPs during development and disease.

Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence

Acute kidney injury (AKI) is a worldwide health problem currently lacking therapeutics that directly promote renal repair or prevent the occurrence of chronic fibrosis. DNA damage is a feature of many forms of kidney injury, and targeting DNA damage and repair might be effective strategies for kidney protection in AKI. Boosting nicotinamide adenine dinucleotide (NAD+) levels is thought to have beneficial effects on DNA damage repair and fibrosis in other organs. However, no kidney-related studies of such effects have been performed to date. Here, we have shown that NMN (an NAD+ precursor) administration could significantly reduce tubular cell DNA damage and subsequent cellular senescence induced by hydrogen peroxide and hypoxia in human proximal tubular cells (HK-2 cells). The DNA damage inhibition, antiaging and anti-inflammatory effects of NMN were further confirmed in a unilateral ischemia-reperfusion injury (uIRI) mouse model. Most importantly, the antifibrosis activity of NMN was also shown in ischemic AKI mouse models, regardless of whether NMN was administered in advance or during the recovery phase. Collectively, these results suggest that NMN could significantly inhibit tubular cell DNA damage, senescence and inflammation. NMN administration might be an effective strategy for preventing or treating kidney fibrosis after AKI.

Role of fibroblast growth factor signalling in hepatic fibrosis.

Fibrotic remodelling is a highly conserved protective response to tissue injury and it is essential for the maintenance of structural and functional tissue integrity. Also hepatic fibrosis can be considered as a wound-healing response to liver injury, reflecting a balance between liver repair and scar formation. In contrast, pathological fibrosis corresponds to impaired wound healing. Usually, the liver regenerates after acute injury. However, if the damaging mechanisms persist, the liver reacts with progressive and uncontrolled accumulation of extracellular matrix proteins. Eventually, excessive fibrosis can lead to cirrhosis and hepatic failure. Furthermore, cirrhosis is the major risk factor for the development of hepatocellular cancer (HCC). Therefore, hepatic fibrosis is the most critical pathological factor that determines the morbidity and mortality of patients with chronic liver disease. Still, no effective anti-fibrogenic therapies exist, despite the very high medical need. The regulation of fibroblast growth factor (FGF) signalling is a prerequisite for adequate wound healing, repair and homeostasis in various tissues and organs. The FGF family comprises 22 proteins that can be classified into paracrine, intracrine and endocrine factors. Most FGFs signal through transmembrane tyrosine kinase FGF receptors (FGFRs). Although FGFRs are promising targets for the treatment of HCC, the expression and function of FGFR-ligands in hepatic fibrosis is still poorly understood. This review summarizes the latest advances in our understanding of FGF signalling in hepatic fibrosis. Furthermore, the potential of FGFs as targets for the treatment of hepatic fibrosis and remaining challenges for the field are discussed.

Root carbon and nutrient homeostasis determines downy oak sapling survival and recovery from drought.

The role of carbon (C) and nutrient uptake, allocation, storage and especially their interactions in survival and recovery of trees under increased frequencies and intensities of drought events is not well understood. A full factorial experiment with four soil water content regimes ranging from extreme drought to well-watered conditions and two fertilization levels was carried out. We aimed to investigate whether nutrient addition mitigates drought effects on downy oak (Quercus pubescens Willd.) and whether storage pools of non-structural carbohydrates (NSC) are modified to enhance survival after 2.5 years of drought and recovery after drought relief. Physiological traits, such as photosynthesis, predawn leaf water potential as well as tissue biomass together with pools and dynamics of NSC and nutrients at the whole-tree level were investigated. Our results showed that fertilization played a minor role in saplings’ physiological processes to cope with drought and drought relief, but reduced sapling mortality during extreme drought. Irrespective of nutrient supply, Q. pubescens showed increased soluble sugar concentration in all tissues with increasing drought intensity, mostly because of starch degradation. After 28 days of drought relief, tissue sugar concentrations decreased, reaching comparable values to those of well-watered plants. Only during the recovery process from extreme drought, root NSC concentration strongly declined, leading to an almost complete NSC depletion after 28 days of rewetting, simultaneously with new leaves flushing. These findings suggest that extreme drought can lead to root C exhaustion. After drought relief, the repair and regrowth of organs can even exacerbate the root C depletion. We concluded that under future climate conditions with repeated drought events, the insufficient and lagged C replenishment in roots might eventually lead to C starvation and further mortality.

Neutrophils promote clearance of nuclear debris following acid-induced lung injury

AbstractNeutrophils are critical mediators of host defense in pathogen-induced and sterile inflammation. Excessive neutrophil activation has been associated with increased host pathology through collateral organ damage. The beneficial aspects of neutrophil activation, particularly in sterile inflammation, are less well defined. We observed accumulation of nuclear debris in the lungs of neutropenic mice exposed to acid-induced injury compared with wild type. Size analysis of DNA debris showed that neutropenic mice were unable to degrade extracellular DNA fragments. In addition, we found that neutrophils are able to differentially express DNA-degrading and repair-associated genes and proteins. Once neutrophils are at sites of lung inflammation, they are able to phagocytose and degrade extracellular DNA. This neutrophil-dependent DNA degradation occurs in a MyD88-dependent pathway. The increased DNA debris in neutropenic mice was associated with dysregulated alveolar repair and the phenotype is rescued by intratracheal administration of DNase I. Thus, we show a novel mechanism as part of the inflammatory response, in which neutrophils engulf and degrade extracellular DNA fragments and allow for optimal organ repair.

Plasma-Rich in Growth Factor and its Clinical Application.

The potential use of growth factors in stem cell-based therapies for the repair and regeneration of tissues and organs offers a paradigm shift in regenerative medicine. Growth factors are critical signalling molecules that play an important role in tissue development and remodelling. Plasma rich in growth factor (PRGF) is a biotechnological strategy for the harvesting of the active substances of platelets, including growth factors, from the patient's blood. Because of their tremendous essential growth factor and bioactive agents, as well as their paracrine mechanisms, PRGF has been used as an efficacious option and adjuvant biological therapy in the repair and replacement of damaged organs. This article provides an overview of PRGF extraction and its properties and critically reviewed its clinical benefit and clinical trials in the treatment and regeneration of human organs. Regenerative medicine is a multi-billion-dollar industry with huge interest to clinicians, academics and industries, being considered as an emerging technology.

Repair cell first, then regenerate the tissues and organs

Wound healing, tissue repair and regenerative medicine are in great demand, and great achievements in these fields have been made. The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly; however, the basic process of repair at the cell level is often neglected. Because the cell is the basic unit of organism structure and function; cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury. Then, damage to tissues and organs occurs with massive cell damage, apoptosis and even cell death. Thus, how to achieve the aim of perfect repair and regeneration? The basic process of tissue or organ repair and regeneration should involve repair of cells first, then tissues and organs. In this manuscript, it is my consideration about how to repair the cell first, then regenerate the tissues and organs.

Decellularization of Small Intestinal Submucosa.

Small intestinal submucosa (SIS) is the most studied extracellular matrix (ECM) for repair and regeneration of different organs and tissues. Promising results of SIS-ECM as a vascular graft, led scientists to examine its applicability for repairing other tissues. Overall results indicated that SIS grafts induce tissue regeneration and remodeling to almost native condition. Investigating immunomodulatory effects of SIS is another interesting field of research. SIS can be utilized in different forms for multiple clinical and experimental studies. The aim of this chapter is to investigate the decellularization process of SIS and its common clinical application.

Research Progress on Tissue Engineering of Main Tissues and Organs of Human Body

The injury and failure diseases of human tissues and organs, such as heart failure and chronic kidney disease, seriously threaten human health and life safety. At present, however, organ transplantation has obvious limitations, and tissue engineering is considered as a potential alternative therapy. Tissue engineering uses the construction of cells, biomaterials and bioreactors to develop three-dimensional artificial tissues and organs for the enhancement, repair and replacement of damaged or diseased tissues and organs, which contributes to the fundamental solutions of diseases of tissues and organs as well as to the improvement of human health. This paper introduces the research progress of tissue engineering technology in the field of living organs from three aspects: seed cells, application of growth factors and biomimetic preparation of functionalized scaffold materials, hoping to provide help and ideas for the research and industrial development of the repair and reconstruction of human organs.

15-Hydroxyprostaglandin dehydrogenase inhibitor prevents contrast-induced acute kidney injury

The two primary mechanisms by which iodinated contrast media (CM) causes contrast-induced acute kidney injury (CIAKI) are the hemodynamic effect causing intrarenal vasoconstriction and the tubular toxic effect causing acute tubular necrosis. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades prostaglandin E2 (PGE2), promotes tissue repair and regeneration in many organs. PGE2 causes intrarenal arterial vasodilation. In this study, we investigated whether a 15-PGDH inhibitor can act as a candidate for blocking these two major mechanisms of CIAKI. We established a CIAKI mouse model by injecting a 10 gram of iodine per body weight (gI/kg) dose of iodixanol into each mouse tail vein. A 15-PGDH inhibitor (SW033291), PGE1, or PGE2 were administered to compare the renal functional parameters, histologic injury, vasoconstriction, and renal blood flow changes. In addition, human renal proximal tubular epithelial cells were cultured in a CM-treated medium. SW033291, PGE1, or PGE2 were added to compare any changes in cell viability and apoptosis rate. CIAKI mice that received SW033291 had lower serum levels of creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1 (p < 0.001); lower histologic injury score and TUNEL positive rates (p < 0.001); and higher medullary arteriolar area (p < 0.05) and renal blood flow (p < 0.001) than CM + vehicle group. In cell culture experiments, Adding SW033291 increased the viability rate (p < 0.05) and decreased the apoptosis rate of the tubular epithelial cells (p < 0.001). This 15-PGDH inhibitor blocks the two primary mechanisms of CIAKI, intrarenal vasoconstriction and tubular cell toxicity, and thus has the potential to be a novel prophylaxis for CIAKI. Abbreviations: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase; AMP: adenosine monophosphate; CIAKI: contrast-induced acute kidney injury; CM: contrast media; EP: prostaglandin E2 receptor; hRPTECs: human-derived renal proximal tubule epithelial cells; KIM-1: kidney injury molecule-1; MTT: 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NGAL: neutrophil gelatinase-associated lipocalin; PBS: phosphate-buffered saline; PGE1: prostaglandin E1; PGE2: prostaglandin E2; RBF: renal blood flow; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; α-SMA: α-Smooth muscle actin