Transplantation of Human Pluripotent Stem Cell-Derived Cardiomyocytes for Cardiac Regenerative Therapy

Cardiovascular disease is the leading cause of death worldwide and bears an immense economic burden. Late-stage heart failure often requires total heart transplantation; however, due to donor shortages and lifelong immunosuppression, alternative cardiac regenerative therapies are in high demand. Human pluripotent stem cells (hPSCs), including human embryonic and induced pluripotent stem cells, have emerged as a viable source of human cardiomyocytes for transplantation. Recent developments in several mammalian models of cardiac injury have provided strong evidence of the therapeutic potential of hPSC-derived cardiomyocytes (hPSC-CM), showing their ability to electromechanically integrate with host cardiac tissue and promote functional recovery. In this review, we will discuss recent developments in hPSC-CM differentiation and transplantation strategies for delivery to the heart. We will highlight the mechanisms through which hPSC-CMs contribute to heart repair, review major challenges in successful transplantation of hPSC-CMs, and present solutions that are being explored to address these limitations. We end with a discussion of the clinical use of hPSC-CMs, including hurdles to clinical translation, current clinical trials, and future perspectives on hPSC-CM transplantation.

THE SIGNIFICANCE OF THE STUDY OF THE LIVER FUNCTION TEST WITHIN POST-TRANSPLANT PATIENTS

In recent years, the survival rate of patients after liver transplantation (LT) has improved significantly. However, successful transplantation is directly related to the proper management of the patient after surgery, including considering essential aspects based on the results of laboratory tests. Therefore, it is essential to study the laboratory characteristics to investigate the functional state of the liver. In the present study, we investigated the indicators of liver function in postoperative patients: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, total bilirubin, gamma-glutamyl transferase (GGT). Venous blood samples were used for investigation. A total of 10 post-transplant patients were studied. Appropriate research methods were used. P<0.05 was considered statistically significant. Overall, our results have shown that intensive examinations of the liver panel in postoperative patients significantly contribute to the proper management of the complicated patient, which directly impacts the final results. Notably, the variability of GGT and ALP may be directly related to the transplanted chronic immune response of the liver and may be used as an early marker for the diagnosis of biliary complications.

Successful transplantation of spermatogonial stem cells into the seminiferous tubules of busulfan-treated mice

Background Spermatogonial stem cells (SSCs) in the testis are crucial for transferring genetic information to the next generation. Successful transplantation of SSCs to infertile men is an advanced therapeutic application in reproductive biology research. Methods In this experimental research, both in vitro and in vivo characterization of undifferentiated and differentiated SSCs were performed by morphology—immunocytochemistry (ICC), immunohistochemistry (IMH), Fluidigm Real-Time polymerase chain reaction (RT-PCR) and flow cytometry analysis. The isolated SSCs were finally microinjected into the rete testis of busulfan-treated mice. The compact undifferentiated and more loosely connected round differentiated SSCs were isolated during testicular cell expansion from their specific feeder layer. Results ICC analysis indicated high and low expression levels of Zbtb16 in undifferentiated and differentiated germ cells. Also, IMH analysis showed different expression levels of Zbtb16 in the two different germ stem cell populations of the testicular tissue. While Fluidigm RT-PCR analysis indicated overexpression of the TAF4B germ cell gene, the expression of DAZL, VASA, and Zbtb16 were down-regulated during the differentiation of SSCs (P < 0.05). Also, flow cytometry analysis confirmed the significant downregulation of Itgb1 and Itga4 during differentiation. By transplantation of SSCs into busulfan-treated NOD/SCID mice, GFP-labeled sperm cells developed. Conclusions In the current study, we performed a transplantation technique that could be useful for the future microinjection of SSCs during infertility treatment and for studying in vivo differentiation of SSCs into sperm.

Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives

With the prevalence of eye diseases, such as cataracts, retinal degenerative diseases, and glaucoma, different treatments including lens replacement, vitrectomy, and stem cell transplantation have been developed; however, they are not without their respective shortcomings. For example, current methods to seal corneal incisions induced by cataract surgery, such as suturing and stromal hydration, are less than ideal due to the potential for surgically induced astigmatism or wound leakage. Vitrectomy performed on patients with diabetic retinopathy requires an artificial vitreous substitute, with current offerings having many shortcomings such as retinal toxicity. The use of stem cells has also been investigated in retinal degenerative diseases; however, an optimal delivery system is required for successful transplantation. The incorporation of hydrogels into ocular therapy has been a critical focus in overcoming the limitations of current treatments. Previous reviews have extensively documented the use of hydrogels in drug delivery; thus, the goal of this review is to discuss recent advances in hydrogel technology in surgical applications, including dendrimer and gelatin-based hydrogels for ocular adhesives and a variety of different polymers for vitreous substitutes, as well as recent advances in hydrogel-based retinal pigment epithelium (RPE) and retinal progenitor cell (RPC) delivery to the retina.

Combination of Drugs and Cell Transplantation: More Beneficial Stem Cell-Based Regenerative Therapies Targeting Neurological Disorders

Cell transplantation therapy using pluripotent/multipotent stem cells has gained attention as a novel therapeutic strategy for treating neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, ischemic stroke, and spinal cord injury. To fully realize the potential of cell transplantation therapy, new therapeutic options that increase cell engraftments must be developed, either through modifications to the grafted cells themselves or through changes in the microenvironment surrounding the grafted region. Together these developments could potentially restore lost neuronal function by better supporting grafted cells. In addition, drug administration can improve the outcome of cell transplantation therapy through better accessibility and delivery to the target region following cell transplantation. Here we introduce examples of drug repurposing approaches for more successful transplantation therapies based on preclinical experiments with clinically approved drugs. Drug repurposing is an advantageous drug development strategy because drugs that have already been clinically approved can be repurposed to treat other diseases faster and at lower cost. Therefore, drug repurposing is a reasonable approach to enhance the outcomes of cell transplantation therapies for neurological diseases. Ideal repurposing candidates would result in more efficient cell transplantation therapies and provide a new and beneficial therapeutic combination.

How Machine Perfusion Ameliorates Hepatic Ischaemia Reperfusion Injury

The increasing disparity between the number of patients listed for transplantation and the number of suitable organs has led to the increasing use of extended criteria donors (ECDs). ECDs are at increased risk of developing ischaemia reperfusion injury and greater risk of post-transplant complications. Ischaemia reperfusion injury is a major complication of organ transplantation defined as the inflammatory changes seen following the disruption and restoration of blood flow to an organ—it is a multifactorial process with the potential to cause both local and systemic organ failure. The utilisation of machine perfusion under normothermic (37 degrees Celsius) and hypothermic (4–10 degrees Celsius) has proven to be a significant advancement in organ preservation and restoration. One of the key benefits is its ability to optimise suboptimal organs for successful transplantation. This review is focused on examining ischaemia reperfusion injury and how machine perfusion ameliorates the graft’s response to this.

Сlinical features of malignant tumors against the background of immunosuppressive therapy in heart transplant recipients

As the survival rate of cardiac recipients improves, higher incidence of malignancy in the late postoperative period becomes essential for their prognosis. Immunosuppressive therapy is one of the key prerequisites for successful transplantation. However, long-term use of immunosuppressive agents increases the incidence of malignant tumors compared to the general population. The risk of their development after organ transplantation increases by 2–4 times compared to the general population. For patients who have undergone transplantation since 2000, the risk of developing malignant neoplasms 1–5 years after surgery is estimated at 10–12%. Timely comprehensive examination of patients, development of new immunosuppression schemes, treatment of those predisposing to the development of malignant neoplasms and giving up harmful habits will reduce the risk of malignant tumors and help diagnose these serious complications at an early stage, which, in turn, will increase the life expectancy of solid organ (particularly the heart) recipients.

MO921PROGNOSTIC OUTCOMES OF TRANSPLANTED KIDNEY USING SOLUBLE CD30 AND Β2- MICROGLOBULIN

Background and Aims Transplantation is the first successful modality of renal replacement therapy (RRT) for irreversible chronic kidney disease (CKD; stage 5). Identifying additional factors associated with poor long-term prognosis after transplantation may provide clues regarding the pathophysiological mechanisms involved in allograft failure and identify high-risk patients who may benefit from additional monitoring or interventions. Successful kidney transplantation results in a substantial decrease in β2M levels, but a delayed decrease or increasing levels after transplantation may serve as a marker of acute rejection or inflammation. Several reports show that elevated sCD30 levels, pre and post transplantation are associated with a poor prognosis for long term kidney graft survival. These studies found higher CD30 levels in allograft recipients and a good predictor of impending acute rejection. The aim of the work is to study the prognostic outcomes of transplanted kidney using CD30 and β2-Microglobulin Method prospective study was conducted in nephrology unit –internal medicine department at Tanta and Kasr El Ainy university ,over 1 year.20 patients subjected to primary Tx.participated in this study.Cd30 and β2M.at day -1,2weeks and 3 months,with clinical follow up after 1 year to detect graft survival Results At day -1,level of cd30 was higher in rejection group than the other patient group.2 weeks post transplantation ,level of cd30 was higher in rejection group than the other patient group and at 3 monthes post transplantation level of cd30 was higher in rejection group than the other patient group,and these differences are statistically highly significant.(p values :0.003 ,0.005 and 0.002 respectively) Successful transplantation leads to significant decrease in serum cd30 at 2 weeks post tx.(P1 &lt;0.005) and at 3 monthes post tx. (P1&lt;0.001) although in rejection group, significant decrease in cd30 was at 2 weeks post tx.only(P1&lt;0.005) and at 3 monthes serum cd30 began to rise again with( P1 0.157). At day -1,level of β2microglobulin was higher in rejection group than the other patient groupwith statistically significant difference (p. 0.01).2 weeks post transplantation ,level of β2microglobulin was higher in rejection group than the other patient groupbut statistically not significant(p. 0.18 ) and at 3 monthes post transplantation level of β2microglobulin was higher in rejection group than the other patient group but statistically non significant(p. 0.18 ). Successful transplantation leads to significant decrease in serum β2microglobulin at 2 weeks post tx.(P1 &lt;0.002) and at 3 monthes post tx. (P1&lt;0.001) although in rejection group ,significant decrease in β2microglobulin was at 3 monthes post tx.only(P1&lt;0.005) and at 2 weeks no significant decrease(p1 0.15) Conclusion pre transplantation high Cd30 and β2M is associated with poor outcome.failure of decrease of cd30 and β2M post Tx. also associated with poor outcome or infection. Successful transplantation leads to significant decrease in serum cd30 and β2M. which can be used as predictors of graft survival with better sensitivity and specificity than serum creatinin.