Abstract:In recent years, there has been an alarming increase in the incidence of diabetes, with one in every eleven individuals worldwide suffering from this debilitating disease. As the available treatment options fail to reduce disease progression, novel avenues such as the bioartificial pancreas are being given serious consideration. In the past decade, the research focus has shifted towards the field of tissue engineering, which helps to design biological substitutes for repair and replacement of non-functional or… Show more
“…However, its murine cancer origin and not well-defined growth factor composition, along with its batch-to-batch variation, are raising more and more questions in the frame of its clinical use. Several approaches involving hydrogels of natural or synthetic polymers, “organ on chip”/bioprinting, and native ECM derived from organ decellularization have been developed to grow organoids from various tissues [ 82 , 83 , 84 , 85 , 86 ]. Surprisingly, only few studies reported the development of Matrigel alternatives specifically for pancreas or PDAC organoids.…”
Pancreatic ductal adenocarcinoma (PDAC) represents 90% of pancreatic malignancies. In contrast to many other tumor entities, the prognosis of PDAC has not significantly improved during the past thirty years. Patients are often diagnosed too late, leading to an overall five-year survival rate below 10%. More dramatically, PDAC cases are on the rise and it is expected to become the second leading cause of death by cancer in western countries by 2030. Currently, the use of gemcitabine/nab-paclitaxel or FOLFIRINOX remains the standard chemotherapy treatment but still with limited efficiency. There is an urgent need for the development of early diagnostic and therapeutic tools. To this point, in the past 5 years, organoid technology has emerged as a revolution in the field of PDAC personalized medicine. Here, we are reviewing and discussing the current technical and scientific knowledge on PDAC organoids, their future perspectives, and how they can represent a game change in the fight against PDAC by improving both diagnosis and treatment options.
“…However, its murine cancer origin and not well-defined growth factor composition, along with its batch-to-batch variation, are raising more and more questions in the frame of its clinical use. Several approaches involving hydrogels of natural or synthetic polymers, “organ on chip”/bioprinting, and native ECM derived from organ decellularization have been developed to grow organoids from various tissues [ 82 , 83 , 84 , 85 , 86 ]. Surprisingly, only few studies reported the development of Matrigel alternatives specifically for pancreas or PDAC organoids.…”
Pancreatic ductal adenocarcinoma (PDAC) represents 90% of pancreatic malignancies. In contrast to many other tumor entities, the prognosis of PDAC has not significantly improved during the past thirty years. Patients are often diagnosed too late, leading to an overall five-year survival rate below 10%. More dramatically, PDAC cases are on the rise and it is expected to become the second leading cause of death by cancer in western countries by 2030. Currently, the use of gemcitabine/nab-paclitaxel or FOLFIRINOX remains the standard chemotherapy treatment but still with limited efficiency. There is an urgent need for the development of early diagnostic and therapeutic tools. To this point, in the past 5 years, organoid technology has emerged as a revolution in the field of PDAC personalized medicine. Here, we are reviewing and discussing the current technical and scientific knowledge on PDAC organoids, their future perspectives, and how they can represent a game change in the fight against PDAC by improving both diagnosis and treatment options.
“…In the last decade, as an alternative to traditional surgical methods of treatment, there was an active development of technologies of tissue engineering and regenerative medicine (TERM) to restore the structure and functions of damaged tissues/organs. These technologies are aimed at creating tissueengineered constructs (TECs), including a tissue-engineered construct of the pancreas (TECP), performing an insulin-producing function [1,2]. The relevance of the search for new methods of treating type 1 diabetes mellitus is beyond doubt.…”
Section: Introductionmentioning
confidence: 99%
“…This problem can be solved by the development of the TECP, often referenced in publications as a bioarti cial pancreas, formed on the basis of pancreatic islets or other insulin-producing cellular components [9] and scaffolds [10,11] which contribute to the preservation of the structure and function of islets in vitro and in vivo. The advantage of using the islets as a cellular component lies in the accumulated secretion of hormones and speci c biologically active endogenous polypeptides by all types of islet cells [1]. The obtainment of the viable functionally active islets where β-cells constitute the main cell population is a de ning step in the development of the TECP.…”
Section: Introductionmentioning
confidence: 99%
“…However, in the process of constructing the TECP, it is necessary to take into account that not only β-cells, but also other types of islet cells participate in its overall functionality. This is the advantage of creating bioarti cial pancreas based on islets [1].…”
The creation of a tissue-engineered structure of the pancreas based on isolated pancreatic islets is hindered by problems associated with maintaining their viability and insulin-producing function. Both biopolymer and tissue-specific scaffolds can contribute to the preservation of the structure and function of pancreatic islets in vitro and in vivo. Comparative morphofunctional analysis in vitro of two different types of tissue-engineered structures of the pancreas, which represent culture systems of isolated islets with biomimetics of an extracellular matrix - a biopolymer collagen-containing scaffold and a tissue-specific scaffold obtained as a result of pancreatic decellularization, - was performed. The results showed that the use of scaffolds in the creation of a tissue-engineered design of the pancreas contributes not only to the preservation of the viability of the islets, but also to the prolongation of their insulin-producing functions, compared to the monoculture of the islets in vitro. A significant increase was found in the basal and stimulated (under glucose load) insulin concentrations in the tissue of engineered structures studied, at the same time the advantage of using a tissue-specific scaffold compared to a biopolymer collagen-containing scaffold was shown. We think that these studies will become a platform for creating a tissue-engineered design of the human pancreas for treatment of type 1 diabetes mellitus.
“…Созданию биомедицинского клеточного продукта -биоинженерной конструкции поджелудочной железы (ПЖ) препятствуют проблемы, связанные с поддержанием жизнеспособности функционально активных изолированных островков Лангерганса (ОЛ) [1,2]. Известно, что в процессе изоляции ОЛ утрачивают васкуляризацию, иннервацию, а также лишаются связей с внеклеточным матриксом (ВКМ), играющим значимую роль в регуляции множества аспектов физиологии островков, включая выживаемость, пролиферацию и секрецию инсулина [3,4].…”
ФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва, Российская Федерация Введение. Созданию биомедицинского клеточного продукта-биоинженерной конструкции поджелудочной железы (ПЖ)-препятствуют проблемы, связанные с поддержанием жизнеспособности функционально активных изолированных островков Лангерганса (ОЛ). Сохранению структуры и функции изолированных ОЛ в условиях in vitro и in vivo могут способствовать как биополимерные, так и тканеспецифические матриксы. Наиболее предпочтительные для клеток тканеспецифические матриксы могут быть получены в результате децеллюляризации поджелудочной железы (ДПЖ-матрикс). Цель. Провести сравнительный анализ секреторной функции изолированных ОЛ крысы, культивированных в присутствии биополимерного коллагенсодержащего гидрогеля (БМКГ) и тканеспецифического ДПЖ-матрикса соответственно. Материалы и методы. ОЛ из ПЖ крысы выделяли, используя классическую коллагеназную технику с некоторыми модификациями. ОЛ культивировали в присутствии БМКГ-и тканеспецифического матрикса в стандартных условиях. Тканеспецифический ДПЖ-матрикс получали в результате децеллюляризации ПЖ крысы. ДПЖ-матрикс был исследован на цитотоксичность, присутствие ДНК и подвергнут морфологическому изучению. Секреторную функцию ОЛ исследовали методом иммуноферментного анализа (ИФА). Результаты. Было показано, что секреторная функция островков, культивированных в присутствии БМКГи ДПЖ-матрикса, значительно выше, чем в монокультуре островков. Выявлено преимущество применения тканеспецифического ДПЖ-матрикса при создании биоинженерной конструкции ПЖ по сравнению с БМКГ-матриксом. Заключение. БМКГ и тканеспецифический ДПЖ-матриксы способствуют не только сохранению жизнеспособности изолированных ОЛ, но и пролонгированию их секреторной способности в течение 10 дней, по сравнению с монокультурой ОЛ.
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