The morphology and application of stem cells in digestive system surgery

Background: Stem cells constitute a group of cells which possess the ability to self-renew as well as the capacity to differentiate into a vast number of different cells within the human organism. Moreover, stem cells are able to undergo a potentially unlimited number of divisions and this characteristic is clinically essential. Specific fields of its application include treatment of diseases mainly in the field of haematology, orthopaedics, surgery, dentistry, and neurology. Materials and methods: In the following work, the current knowledge concerning mechanisms of stem cell treatment in different parts of the digestive system with its diseases as well as adjacent therapy for surgery has been revised. Results: Stem cells therapy may be used in the treatment of various diseases of different parts of the digestive system. This also applies to the end part of the digestive tract (proctological diseases) because stem cells can be used to treat fistulas. Liposuction allows more recovery of mesenchymal stem cells, compared to previous bone marrow harvesting methods. Despite the application of stem cells in the treatment of different diseases used for many years so far, the therapeutic use for the regeneration of the gastrointestinal tract is still rare and unfamiliar. Conclusions: Regenerative medicine seems to be a promising tool in medical research, especially when insulated cells and designed biomaterials are taken into consideration. Major points of discussion include types of stem cells, their origin or differentiation for the treatment of many diseases

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA\u27s research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC

Challenges and possible clinical applications of human embryonic stem cell research

Human embryonic stem cells (hESC) are harvested from the inner cell mass of the pre-implantation embryo and possess several unique characteristics. First, they are self-renewing, meaning they can grow indefinitely in an appropriate culture environment and secondly, they are pluripotent, which means they have the potential to become nearly every cell of the human body. Consequently, hESC offer a unique insight into basic human development in vitro, allow better understanding of the genetic and molecular controls of these processes, and are of pharmaceutical interest to test or develop new drugs. The most exciting and high-profile potential application of hESC research is the possibility that such cells can be used for regenerative medicine. Still, several obstacles have to be overcome before clinical applications can be considered: (i) xeno-free derivation and culture of hESC is necessary; (ii) hESC should be safe after transplantation and (iii) their identity and behaviour should be well-known

Regenerative medicine for childhood gastrointestinal diseases

Several paediatric gastrointestinal diseases result in life-shortening organ failure. For many of these conditions, current therapeutic options are suboptimal and may not offer a cure. Regenerative medicine is an inter-disciplinary field involving biologists, engineers, and clinicians that aims to produce cell and tissue-based therapies to overcome organ failure. Exciting advances in stem cell biology, materials science, and bioengineering bring engineered gastrointestinal cell and tissue therapies to the verge of clinical trial. In this review, we summarise the requirements for bioengineered therapies, the possible sources of the various cellular and non-cellular components, and the progress towards clinical translation of oesophageal and intestinal tissue engineering to date

The Importance of HLA assessment in "off-the-Shelf" allogeneic mesenchymal stem cells based-therapies

The need for more effective therapies of chronic and acute diseases has led to the attempts of developing more adequate and less invasive treatment methods. Regenerative medicine relies mainly on the therapeutic potential of stem cells. Mesenchymal stem cells (MSCs), due to their immunosuppressive properties and tissue repair abilities, seem to be an ideal tool for cell-based therapies. Taking into account all available sources of MSCs, perinatal tissues become an attractive source of allogeneic MSCs. The allogeneic MSCs provide "off-the-shelf" cellular therapy, however, their allogenicity may be viewed as a limitation for their use. Moreover, some evidence suggests that MSCs are not as immune-privileged as it was previously reported. Therefore, understanding their interactions with the recipient’s immune system is crucial for their successful clinical application. In this review, we discuss both autologous and allogeneic application of MSCs, focusing on current approaches to allogeneic MSCs therapies, with a particular interest in the role of human leukocyte antigens (HLA) and HLA-matching in allogeneic MSCs transplantation. Importantly, the evidence from the currently completed and ongoing clinical trials demonstrates that allogeneic MSCs transplantation is safe and seems to cause no major side-effects to the patient. These findings strongly support the case for MSCs efficacy in treatment of a variety of diseases and their use as an “off-the-shelf” medical product

Cancer Biomarkers and Targets in Digestive Organs

Identification and development of cancer biomarkers and targets have greatly accelerated progress towards precision medicine in oncology. Studies of tumor biology have not only provided insights into the mechanisms underlying carcinogenesis, but also led to discovery of molecules that have been developed into cancer biomarkers and targets. Multi-platforms for molecular characterization of tumors using next-generation genomic sequencing, immunohistochemistry, in situ hybridization, and blood-based biopsies have greatly expanded the portfolio of potential biomarkers and targets. These cancer biomarkers have been developed for diagnosis, early detection, prognosis, and prediction of treatment response. The molecular targets have been exploited for anti-cancer therapy and delivery of therapeutic agents. This Special Issue of Biomedicines focuses on recent advances in the discovery, characterization, translation, and clinical application of cancer biomarkers and targets in malignant diseases of the digestive system. The goal is to stimulate basic and translational research and clinical collaboration in this exciting field with the hope of developing strategies for prevention and early detection/diagnosis of cancer in digestive organs, and improving therapeutic and psychosocial outcomes in patients with these malignant diseases

The role of Mesenchymal Stem Cells in the development of ATMPs

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2022, Universidade de Lisboa, Faculdade de Farmácia.Os Advanced Therapy Medicinal Products (ATMPs) tornaram-se uma realidade com a evolução da pesquisa científica e tecnologia, que levaram à evolução terapêutica sentida nos últimos anos. Estas terapêuticas compartilham as funcionalidades gerais de um medicamento - funções farmacológicas, imunológicas ou metabólicas - e, para além disto, apresentam um perfil biológico e atuam como uma importante opção terapêutica para doenças para as quais não existem alternativas. Estas características biológicas acarretam preocupações extra em termos de regulamentação, acesso ao mercado e a nível ético, que são exploradas neste trabalho. As células estaminais mesenquimais (MSCs) são células multipotentes capazes de se diferenciar em células da linhagem mesodérmica, mantendo a sua própria existência por auto-renovação, possuindo também diversas funções imunomoduladoras e um secretoma rico em fatores tróficos, entre outras. O conjunto destas características constitui a oportunidade perfeita para o desenvolvimento de ATMPs derivados de MSCs, direcionados a várias áreas terapêuticas e aplicações, tema este que tem sido um dos focos da comunidade científica. O perfil imunomodulador que as MSCs apresentam, em particular, é uma “mina de ouro” no que toca ao controlo das disfunções do Sistema Imunitário e o seu modus operandi é uma fonte de esperança na procura de melhores tratamentos para doenças autoimunes, que prejudicam a qualidade de vida dos pacientes. Doenças como a Doença do Enxerto versus Hospedeiro, Osteoartrite, Artrite Reumatoide, Esclerose Múltipla, Lúpus Eritematoso Sistémico, Doença Inflamatória Intestinal e Diabetes Tipo 1 têm agora a possibilidade de obter mais alternativas terapêuticas e os medicamentos com MSCs já aprovados comprovam este facto, juntamente com o grande número de ensaios clínicos com estas indicações. No entanto, apesar destas terapêuticas apresentarem um grande potencial e benefícios para o paciente, a fase de desenvolvimento terapêutico não tem sido fácil e têm surgido desafios significativos no caminho para um maior progresso. Este trabalho destaca os principais mecanismos da terapêutica com MSCs em cada doença autoimune referida, a fim de identificar suas vantagens e detetar possíveis pontos de melhoria no desenvolvimento da terapia de MSC.Advanced Therapy Medicinal Products (ATMPs) became a reality with the development of scientific research and technology, that made the recent years’ therapeutic evolution possible. These therapies share the general functionalities of common medicines - pharmacological, immunological or metabolic functions - and, in addition, present a biological profile and act as an important therapeutic option for diseases without other alternatives. These biological characteristics carry extra burdens regulation-wise, in market access and ethically, that are explored in this work. Mesenchymal Stem Cells are multipotent and capable of differentiating into cells from the mesodermal lineage whilst maintaining their own existence by self-renewing, also carrying several immunomodulatory functions and a secretome with abundant trophic factors, among others. These characteristics make up the perfect opportunity for the development of MSC ATMPs, directed to various therapeutic fields and applications, a subject that has been a focus of the scientific community. The immunomodulatory profile MSCs present, in particular, is a “golden mine” regarding the idea of controlling dysfunctions of the Immune System, and their modus operandi is a source of hope for the achievement of better treatment for autoimmune diseases that taunt patients’ quality of life. Diseases such as Graft Versus Host Disease, Osteoarthritis, Rheumatoid Arthritis, Multiple Sclerosis, Systemic Lupus Erythematosus, Inflammatory Bowel Diseases and Type 1 Diabetes can now gain further therapeutic alternatives and the already approved MSC medicines verify this fact, along with the vast number of clinical trials with these indications. However, even though these therapies may present great potential and benefits for the patient, the development phase hasn’t been easy and significant challenges have arisen against higher progress. This work underlines the major mechanisms of MSC therapy in each referred autoimmune disease, in order to pinpoint their advantages and detect possible improvement points in MSC therapy development