Transplantation Of Human Tissue Research Articles

О необходимости совершенствования нормативно-правового регулирования в части оказания медицинской помощи пациентам до и после трансплантации органов.

The article substantiates a set of problems associated with imperfect legislation regarding mechanisms for regulating the provision of medical care to patients before and after organ transplantation. The authors show that the current legislation does not define who is the attending physician of a patient awaiting and undergoing an organ transplant, and the legal context for organizing such medical care is not substantiated. This may pose significant risks to patients, reduce the quality of medical care provided, and adversely affect the function of the transplanted organ. Based on the analysis carried out, the article makes specific proposals for making additions to the current specialized procedure for providing medical care and the law of the Russian Federation “On transplantation of human organs and (or) tissues.”

Abstract 4188: Kyinno PBMC humanized mouse platform: Pioneering service in biomedical research

Abstract Tumor immunotherapy is the use of the human immune system to kill tumors. Compared with traditional chemotherapy and radiotherapy, immunotherapy has significant advantages such as significant efficacy, long-lasting effects, and low toxicity. Wild-type mice are widely used as preclinical models for immunotherapy due to their normal immune system, but they have many shortcomings, such as only being able to inoculate mouse tumor cells, differences between mouse and human immune systems, etc., which cannot accurately simulate the interaction between drugs and tumor cells in the human body. Humanized mouse models include PBMCs humanized mouse models, HSC humanized mouse models, and human embryonic bone, liver, and thymus tissue (BLT) transplantation models. Among them, the PBMCs humanized mouse model is widely used due to its simple preparation, short cycle, and high levels of hCD3+ T cells in the peripheral blood of mice. To assist in the development of immunotherapy, KYINNO has established a PBMC humanized mouse platform that can perform in vivo drug efficacy verification of various immunotherapeutic drugs such as CD3 bispecific antibodies or multi-specific antibodies, immune checkpoint inhibitors, etc. We screen many PBMC donors and select PBMC donors with light GvHD and good hCD3+ T cell reconstruction effects. The drug administration window of the PBMC humanized model has been extended to 6 weeks. Platform verification has been performed on subcutaneous and intravenous injection models of various tumors. Overall, we successfully established the PBMC humanized mouse platform, which is a powerful tool for immunotherapy. Citation Format: Tongtong Liu, Guojin Wu, Feng He, Longtan Luo, Zhengcheng Guo, Shuliang Li, Jinying Ning, Feng Hao. Kyinno PBMC humanized mouse platform: Pioneering service in biomedical research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4188.

Legal regulation of human somatic rights: transplantation of human organs and biological tissues in Ukraine and foreign countries

The article examines the problems of legal regulation of transplantation of organs and tissues of the human body in Ukraine and foreign countries. Emphasis is placed on legal and ethical difficulties arising in the field of transplantology. It is noted that the right to «mechanize the body» has a number of specific features, namely: the specific nature of the object of these rights - the human body, which is the object of property rights and currently has mainly a monetary value expression; natural dependence on knowledge of biology, genetics, medicine, technology. Their existence and implementation are possible only with the help of achievements of scientific and technical progress; novelty, which has a different degree of expression, depending on the type of protected result of disposal of body or life; ambiguous attitude from the side of religion, morality, ethics, politics; inextricable connection with constitutional (fundamental) human rights in view of the special connection with personal (natural) rights and the peculiarity as an independent group of human rights; exclusivity in terms of its legal consequences in the process and as a result of their implementation. With any change in the physical embodiment of a person, the subjective aspect of legal relations changes, that is, many connections of various branches of legal regulation (civil, marital and family, constitutional, etc.) are affected; the degree of their recognition and implementation reflects the level of development of the state and society in general, etc. It is emphasized that individual somatic rights are reflected both in the legislation of Ukraine and in the legislation of foreign countries. For example, the right to transplant organs in national legislation is not used as a right to dispose of one's body, but as a certain necessity, a medical indication. In order to regulate the issue of organ donation, the legislation of individual states prescribes the practice of establishing special procedures for obtaining the donor's consent to extract a transplant from him (Belgium, Greece, Turkey). Given the lack of transplants for transplant operations, it is important to develop educational work at the state level, explaining to citizens the need to issue voluntary consents for the posthumous use of their donor material. It is worth making proposals for the development and adoption of the State Program of Ukraine aimed at the development of donation. This program should provide organizational, legal and preventive state measures for the promotion and development of legal donation in Ukraine; proposals for the development of a national legal mechanism aimed at encouraging voluntary posthumous donation, which would be based on the lifetime legally formalized consent of potential donors to the posthumous free use of their donor material.

Activated Human Adipose Tissue Transplantation Promotes Sensorimotor Recovery after Acute Spinal Cord Contusion in Rats.

Traumatic spinal cord injuries (SCIs) often result in sensory, motor, and vegetative function loss below the injury site. Although preclinical results have been promising, significant solutions for SCI patients have not been achieved through translating repair strategies to clinical trials. In this study, we investigated the effective potential of mechanically activated lipoaspirated adipose tissue when transplanted into the epicenter of a thoracic spinal contusion. Male Sprague Dawley rats were divided into three experimental groups: SHAM (uninjured and untreated), NaCl (spinal cord contusion with NaCl application), and AF (spinal cord contusion with transplanted activated human fat). Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured to assess endogenous inflammation levels 14 days after injury. Sensorimotor recovery was monitored weekly for 12 weeks, and gait and electrophysiological analyses were performed at the end of this observational period. The results indicated that AF reduced endogenous inflammation post-SCI and there was a significant improvement in sensorimotor recovery. Moreover, activated adipose tissue also reinstated the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions. This investigation highlights the efficacy of activated adipose tissue grafting in acute SCI, suggesting it is a promising therapeutic approach for spinal cord repair after traumatic contusion in humans.

State of Transplantation in the Republic Of Uzbekistan: Existing Problems of Donation.

Organ traTransplantation is one of the most successful achievements in modern medicine. For patients with end-stage chronic renal failure, transplantation undeniably improves their quality of life. The purpose of the study was to discuss the latest scientific data on the state of kidney transplantation in the world and to give an idea of the advantages, opportunities, and problems of kidney transplantation in the world and in the Republic of Uzbekistan. Transplantation in Uzbekistan developed in 5 stages. Stage I (1972-1991) began with the first kidney transplant in Uzbekistan on September 14, 1972, on the basis of the legislation on organ and tissue transplantation of 1970. Stage II (1991-1998) represented a break in the field of transplantation due to its prohibition by law. Stage III (1998-2017) comprised a series of 48 kidney transplants from living related donors on the basis of an order of the Ministry of Health of the Republic of Uzbekistan. Stage IV (2017-2022) comprised a series of 849 kidney transplants and 22 liver transplants from living related donors on the basis of Cabinet of Ministers Resolution No. 859 of October 17, 2017. Stage V began on May 11, 2022, with the adoption of the a new of the Republic of Uzbekistan, On Transplantation of Human Organs and Tissues. According to this new law, the objects of transplantation can be human organs and (or) tissues taken from either a living donor or a deceased donor. This law will expand the range of donors for patients in need. Transplantology is a sphere of life activity that can no longer be ignored; therefore, it is necessary to develop and implement humanistic principles on the basis of which it will be regulated.

Testing of tissue specimens obtained from SARS-CoV-2 nasopharyngeal swab-positive donors

Risk for transmission of SARS-CoV-2 through allogeneic human tissue transplantation is unknown. To further evaluate the risk of virus transmission, tissues were obtained from deceased donors who had tested positive for SARS-CoV-2 RNA via nasopharyngeal swab. This study evaluated an array of human tissues recovered for transplantation, including bone, tendon, skin, fascia lata, vascular tissues, and heart valves. Tissue samples and plasma or serum samples, if available, were tested for viral RNA (vRNA) using a real time PCR system for the presence of virus RNA. All samples were tested in quadruplicate for both subgenomic (sgRNA) and genomic (gRNA) RNA encoding the SARS-CoV-2 nucleocapsid gene. Amplification of a cellular housekeeping gene served as the positive control for every sample. A total of 47 tissue samples from 17 donors were tested for SARS-CoV-2 RNA. Four donors had plasma or serum available for paired testing. SARS-CoV-2 RNA was not detected from any tissue or plasma/serum sample tested. Based on these findings, risk of transmission through the transplantation of tissue types studied from SARS-CoV-2 infected donors is likely to be low.

Genesis of Legal Regulation of Human Organ and Tissue Transplantation in the Russian Federation

The authors explore the genesis of human organ and tissue transplantation in our country and the legal relations arising in this connection. For a long time, this area of medical activity was not regulated at the legislative level. Prior to 1917, the issues of transplantation were predominantly theoretical. In the Soviet period of the history of the Russian state, the development of public medicine and numerous military conflicts confirmed the applied nature of experiments on human organ and tissue transplantation. During this period, rapid development of legislation also affected healthcare. The legal presumption of consent to the removal of organs and (or) tissues was formulated, which established the legal framework for donation of human organs and tissues. At the same time, until 1992, the issues of transplantation were regulated mainly by departmental acts of the USSR Ministry of Health. The Law of the Russian Federation “On Transplantation of Human Organs and (or) Tissues” adopted in 1992 determined that the legal regulation of transplantation issues, including the list of transplantation objects, is determined by the federal executive body in the field of healthcare together with the Russian Academy of Sciences. The current level of development of experimental medicine, including transplantology, makes it necessary to regularly supplement the legislation in this area. For example, only on May 1, 2022, transplantation objects were supplemented with hematopoietic stem cells, and gaps in the legal regulation of pediatric transplantation were eliminated. The authors conclude that our country has significant experience in the field of transplantation and a quite perfect legislative framework. However, work on adjusting the current legislation, adopting new laws and by-laws in this area should not stop.

Optimizing Immature Testicular Tissue and Cell Transplantation Results: Comparing Transplantation Sites and Scaffolds.

For patients who had testicular tissue cryopreserved before receiving gonadotoxic therapies, transplantation of testicular tissues and cells has been recommended as a potential therapeutic option. There are no studies that indicate the generation of sperm after human immature testicular tissue (ITT) or spermatogonial stem cells (SSCs) transplantation. The use of releasing scaffolds and localized drug delivery systems as well as the optimizing transplantation site can play an effective role in increasing the efficiency and improving the quality of testicular tissue and cell transplantation in animal models. Current research is focused on optimizing ITT and cell transplantation, the use of releasing scaffolds, and the selection of the right transplantation site that might restore sperm production or male infertility treatment. By searching the PubMed and Google Scholar databases, original and review papers were collected. Search terms were relevant for SSCs and tissue transplantation. In this review, we'll focus on the potential advantages of using scaffolds and choosing the right transplantation site to improve transplantation outcomes.

Generation of the NeoThy mouse model for human immune system studies.

Humanized mouse models, created via transplantation of human hematopoietic tissues into immune-deficient mice, support a number of research applications, including transplantation immunology, virology and oncology studies. As an alternative to the bone marrow, liver, thymus humanized mouse, which uses fetal tissues for generating a chimeric human immune system, the NeoThy humanized mouse uses nonfetal tissue sources. Specifically, the NeoThy model incorporates hematopoietic stem and progenitor cells from umbilical cord blood (UCB) as well as thymus tissue that is typically discarded as medical waste during neonatal cardiac surgeries. Compared with fetal thymus tissue, the abundant quantity of neonatal thymus tissue offers the opportunity to prepare over 1,000 NeoThy mice from an individual thymus donor. Here we describe a protocol for processing of the neonatal tissues (thymus and UCB) and hematopoietic stem and progenitor cell separation, human leukocyte antigen typing and matching of allogenic thymus and UCB tissues, creation of NeoThy mice, assessment of human immune cell reconstitution and all experimental steps from planning and design to data analysis. This entire protocol takes a total of ~19 h to complete, with steps broken up into multiple sessions of 4 h or less that can be paused and completed over multiple days. The protocol can be completed, after practice, by individuals with intermediate laboratory and animal handling skills, enabling researchers to make effective use of this promising in vivo model of human immune function.

On the Principle of Voluntary Consent to Organ Donation in the Legal Acts of the Russian Federation and International Law

The development of transplantation in the Russian Federation raised in addition to ethical some legal issues, like the conflict of the Law of the Russian Federation “On transplantation of human organs and tissues” and the Federal Law “On burial and funeral business”. Goals and tasks of the research. The main goal of the study is to determine the content of the principle of presumed consent and its legal boundaries. This goal led to the setting of the following tasks: firstly, on the basis of international and national law, to establish the donation procedure, and, secondly, to analyze the practice of the Constitutional Court of the Russian Federation and the European Court of Human Rights on the legality of the principle of presumed consent. Methods. For the study, both general scientific methods like analysis, synthesis, deduction and induction were used, as well as private scientific methods, the main role played the comparative legal method. Guided by it, the author compared the approaches to the legal regulation of donation in various legislative acts of the Russian Federation and international law. Comparative analysis was used to study the practice of the Constitutional Court of the Russian Federation and the ECHR case law. Brief conclusion. The author reveals two models of legal regulation of donation – presumed and requested consent. After studying the Law of the Russian Federation “On transplantation of human organs and tissues” and the Federal Law “On the basics of health protection of citizens in the Russian Federation”, the author suggests ways of improving the national legislation on posthumous donation.

A retrospective hospital benefit and cost analysis of the management of human tissues for orthopaedic allografts

ObjectivesThe transplantation of human tissues is a greatly expanding field of medicine with unquestionable benefits that raise questions about safety, quality and ethics. Since 1 October 2019, the Fondazione Banca...

Educational Actions to Raise Student Awareness About the Donation and Transplantation of Human Organs and Tissues

In Brazil, family refusal to donate organs and tissues is the main reason for not performing transplants, making it necessary to implement different educational strategies in diverse populations on this topic. Thus, this study aimed to raise awareness among school-aged adolescents about the method of organ and tissue donation and transplantation. This is a descriptive experience report with a quantitative and qualitative approach to educational actions in the school environment, mediated by the action research method, carried out with 936 students aged between 14 and 18 years from public schools in the interior of Sao Paulo, Brazil. These actions were developed according to the themes identified and worked on through the culture circle, using active methodologies. Two semistructured questionnaires were applied, pre- and postinterventions. For analysis, sample normality tests and Student's t test were used (P < .0001). The topics identified were as follows: clarifications on the legislative history of donation and transplants; diagnosis of brain and circulatory death; bioethical aspects of transplants; reflections on mourning, death, and dying; maintenance and notification of the potential donor; types of viable organs and tissues for donation; and the process from collection to transplantation, among others. Comparative analysis showed statistical differences between pre- and postinterventions. Educational interventions through active methodologies are presented as tools capable of making students aware of organ and tissue donation and transplantation.

Models of Quality Management Systems Applied in Specialized Services for the Donation and Transplantation of Human Organs and Tissues

BackgroundQuality management tools and models are used to improve processes and products, including those related to organ and tissue donation and transplantation protocols. This study aims to map, discuss, and disseminate models/tools of quality management systems applied in health services, specializing in the donation and/or transplantation of human organs and tissues. MethodsThis is an integrative literature review over the last 10 years, operationalized through searches carried out on the PubMed portal and the databases: SciVerse Scopus (SCOPUS), Scielo, Latin American and Caribbean Literature on Health Sciences (LILACS), Nursing Database (BDENF), and the Virtual Health Library (BVS). The organization of search results in the databases and the election of articles compatible with the guiding question and the inclusion and exclusion criteria for this study took place through the online and free application platform Rayyan. ResultsSix hundred seventy-eight records were found, of which, after careful analysis, 18 articles were considered relevant to the theme. We identified 17 quality management models and/or tools that emphasize using scientifically proven and/or validated techniques to reduce or eliminate the possibility of risks in the processes that permeate the stages of donation and transplantation of organs and tissues. ConclusionThis review brought the possible tools used and published, which can be perceived, reproduced, and improved, through the role of the multidisciplinary team in specialized centers for the donation and transplantation of human organs and tissues, aiming to offer a process of continuous improvement management to deliver better products and services.

Forced Organ Harvesting

Forced Organ Harvesting

Real-world data on renal transplantations from a tertiary-care hospital in North India, in context of Indian regulatory act-transplantation of human organs and tissues act (THOTA): A retrospective analysis

IntroductionRenal transplantation is the treatment of choice for patients suffering from end stage renal disease (ESRD). Indian regulations defined under Transplantation of Human Organs and Tissues Act (THOTA), 2014 restricts organ donations to near-related living donors to curb any malpractices like ‘paid donors’ in living-donor kidney transplantation (LDKT). The aim of our study was to look at real-world data of donor-recipient pairs and to identify relationship of donors (with their respective patients) and the common (or uncommon) DNA profiling methods used for supporting “claimed relationship” in accordance with the regulations. Material and methodsThe donors were categorized and grouped into near-related donor, donors other than near-related donors, swap donors and deceased donors. Claimed relationship was confirmed, commonly by HLA typing, using SSOP method. In few cases, which were uncommon (and infrequent), autosomal DNA analysis, mitochondrial DNA analysis and Y-STR DNA analysis were performed to support the claimed relationship. Data collected included age, gender, relationship, DNA profiling test method. ResultsAmong the 514 donor-recipient pairs evaluated, numbers of female donors out-numbered male donors. The decreasing order of relationships in near-related donor group were wife>mother>father>sister>son>brother>husband> daughter>grandmother. 11.9% of donors were in the category of donors other than near-related donors. In 97.86% cases, the claimed relationship was supported by HLA typing and in just 2.1% cases autosomal DNA analysis>mitochondrial DNA analysis> Y-STR DNA analysis, in this order, were performed to establish relationship. ConclusionThis study brought out gender disparity with women out-numbering men as donors. Among recipients, access to renal transplant was largely restricted to men. As far as relationship of donors to recipients was concerned, mostly near-related family members, like wife, were donors and claimed relationship was almost always (99%) was corroborated by HLA typing.

Aspects related to biofilm production and antifungal susceptibility of clinically relevant yeasts of the genus Trichosporon.

Trichosporonosis corresponds to a systemic fungal disease that leads to high mortality rates and is frequently associated with medical devices. It affects immunosuppressed patients in particular and is strongly linked to acquired human immunodeficiency, organ and tissue transplants, and malignant hematologic diseases such as leukemia and lymphomas. Trichosporon infections have been increasingly reported worldwide; however, little information is available either about their characteristics or the causative microorganism. Thus, the aims of the present study were: to investigate 59 yeasts of the genus Trichosporon by verifying the biofilm formation capacity of isolates; to analyze the susceptibility patterns of planktonic cells against the antifungals fluconazole, itraconazole, amphotericin-B, voriconazole, and caspofungin by comparing European Committee for Antimicrobial Susceptibility Testing (EUCAST) broth microdilution technique with the commercial method Etest; and to assess the susceptibility patterns of biofilm cells (sessile) against the same antifungals through broth microdilution. The ability to form biofilm on the surface of polystyrene plates was noted for all isolates, and 54.3% of samples were considered strong producers. Comparison between the antifungal susceptibility techniques evidenced that Etest showed higher and discordant minimum inhibitory concentrations (MICs) from those obtained by the microdilution method, especially for fluconazole, itraconazole, and caspofungin. Considering the susceptibility of biofilms, most species had high MIC50 and MIC90 against the tested antifungals, showing 4-to-66-fold higher concentrations for amphotericin B and 2-to-33-fold greater concentrations for caspofungin. These results highlight the importance of further studies with Trichosporon spp. for comparison between laboratory findings and in vivo response, considering both the susceptibility tests and the behavior of biofilm cells against drugs.

Organ trafficking and the legal framework in India: a critical analysis of the transplantation of human organs and tissues act, 1994

Organ trafficking, due to its subtle nature, is a less-addressed form of trafficking, among others. It has been decades that the first-ever successful organ transplantation took place. Since then, medical science has advanced in leaps and bounds to gift us another chance of life, even in cases of acute organ failures. However, this has created a huge demand for transplantable organs building an unbridgeable gap between its demand and supply, which on the other hand, has generated booming markets for the illegal sale of organs leading to organized crime of organ trafficking, especially in the developing nations. The Transplantation of Human Organs Act (THOA), 1994, was enacted to provide regulatory frameworks and prevent the commercialization of human organs in India. Although THOA, with its latest amendments and rules, is somewhat successful in curbing the menace, recent studies show that it has failed to achieve its goals largely. The authors in this paper argue that the existing laws in India dealing with organ trades and trafficking are inadequate, in comprehensive, and lags far behind compared to the advancements in medical technologies and report the findings of a systematic analysis of THOA, highlight inadequacies, and recommends relevant reforms.

Overcoming Challenges of Deceased Organ Donation in Indian Private Hospitals.

Overcoming Challenges of Deceased Organ Donation in Indian Private Hospitals.

Aspergillosis of the brain: diagnostic difficulties. Case report

Background: Neuroaspergillosis has nonspecific clinical manifestations and a severe course. Cases of central nervous system aspergillosis are becoming more frequent. Its lifetime diagnosis is very difficult. At the same time, a timely diagnosis makes it possible to conduct an adequate specific therapy and save the patient's life.&#x0D; Clinical case description: We report a clinical case of a patient with a lethal damage to the brain by filamentous fungi, who did not have the risk factors described in the literature human immunodeficiency virus (HIV), neutropenia, organ and tissue transplantation, long therapy with immunosuppressive drugs or corticosteroids.&#x0D; Conclusion: One needs to consider a possibility of this pathology in patients even in the absence of a fever and immunodeficiency conditions. A specific study of biological fluids for the presence of the galactomannan antigen may allow one to establish a timely correct diagnosis and apply an adequate treatment.

Xenograft model of heterotopic transplantation of human ovarian cortical tissue and its clinical relevance.

Xenografts of human ovarian cortical tissue provide a tractable model of heterotopic autotransplantation that is used for fertility preservation in patients undergoing ablative chemo/radiotherapy. This study describes the behavior of hundreds of xenografts to establish a framework for the clinical function of ovarian cortex following autotransplantation over short- and long-term intervals. More than 200 live births have been achieved using autotransplantation of cryopreserved ovarian cortical fragments, yet challenges remain to be addressed. Ischemia of grafted tissue undermines viability and longevity, typically requiring transplantation of multiple cortical pieces; and the dynamics of recruitment within a graft and the influence of parameters like size and patient age at the time of cryopreservation are not well-defined. Here, we describe results from a series of experiments in which we xenografted frozen/thawed human ovarian tissue (n = 440) from 28 girls and women (age range 32 weeks gestational age to 46 years, median 24.3 ± 4.6). Xenografts were recovered across a broad range of intervals (1-52 weeks post-transplantation) and examined histologically to quantify follicle density and distribution. The number of antral follicles in xenografted cortical fragments correlated positively with the total follicle number and was significantly reduced with increased patient age. Within xenografts, follicles were distributed in focal clusters, similar to the native ovary, but the presence of a leading antral follicle coincided with increased proliferation of surrounding follicles. These results underscore the importance of transplanting ovarian tissue with a high density of follicles and elucidate a potential paracrine influence of leading antral follicles on neighboring follicles of earlier stages. This temporal framework for interpreting the kinetics of follicle growth/mobilization may be useful in setting expectations and guiding the parameters of clinical autotransplantation.