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Regenerative medicine of pancreatic islets.

ABSTRACT: The pancreas became one of the first objects of regenerative medicine, since other possibilities of dealing with the pancreatic endocrine insufficiency were clearly exhausted. The number of people living with diabetes mellitus is currently approaching half a billion, hence the crucial relevance of new methods to stimulate regeneration of the insulin-secreting ?-cells of the islets of Langerhans. Natural restrictions on the islet regeneration are very tight; nevertheless, the islets are capable of physiological regeneration via ?-cell self-replication, direct differentiation of multipotent progenitor cells and spontaneous ?- to ?- or ?- to ?-cell conversion (trans-differentiation). The existing preclinical models of ?-cell dysfunction or ablation (induced surgically, chemically or genetically) have significantly expanded our understanding of reparative regeneration of the islets and possible ways of its stimulation. The ultimate goal, sufficient level of functional activity of ?-cells or their substitutes can be achieved by two prospective broad strategies: ?-cell replacement and ?-cell regeneration. The "regeneration" strategy aims to maintain a preserved population of ?-cells through in situ exposure to biologically active substances that improve ?-cell survival, replication and insulin secretion, or to evoke the intrinsic adaptive mechanisms triggering the spontaneous non-?- to ?-cell conversion. The "replacement" strategy implies transplantation of ?-cells (as non-disintegrated pancreatic material or isolated donor islets) or ?-like cells obtained ex vivo from progenitors or mature somatic cells (for example, hepatocytes or ?-cells) under the action of small-molecule inducers or by genetic modification. We believe that the huge volume of experimental and clinical studies will finally allow a safe and effective solution to a seemingly simple goal-restoration of the functionally active ?-cells, the innermost hope of millions of people globally.

SUBMITTER: Arutyunyan IV

PROVIDER: S-EPMC7304103 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Regenerative medicine of pancreatic islets.

Arutyunyan Irina V IV Fatkhudinov Timur Kh TK Makarov Andrey V AV Elchaninov Andrey V AV Sukhikh Gennady T GT

World journal of gastroenterology 20200601 22

The pancreas became one of the first objects of regenerative medicine, since other possibilities of dealing with the pancreatic endocrine insufficiency were clearly exhausted. The number of people living with diabetes mellitus is currently approaching half a billion, hence the crucial relevance of new methods to stimulate regeneration of the insulin-secreting β-cells of the islets of Langerhans. Natural restrictions on the islet regeneration are very tight; nevertheless, the islets are capable o ...[more]

PMID: 32587441

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Project description:The field of regenerative medicine is growing rapidly with the introduction of new therapies that have the potential to treat and cure serious medical conditions, including rare diseases, for which there are no available treatments. In the United States, the development of novel medical products is regulated and guided by the Food and Drug Administration (FDA). As scientific and technological advances are discovered and adopted by the medical industrial enterprise, the FDA's implementation of policies that create a climate conducive to safe development and rapid availability of novel medical products is one of the pillars which support the Agency's mission of protecting and promoting the public health. With advancements in cell modifications and tissue engineering, innovative creation of biomaterials, adoption of three-dimensional bioprinting, and rapid development of human genome editing technologies, the need for Agency's work in ensuring that its science-based policies remain relevant and helpful in facilitating the availability of new treatments to the most vulnerable populations of patients becomes more pressing than ever before. In December 2016, Congress amended section 506 of the Food, Drug, and Cosmetic (FD&C) Act [21 U.S.C. 356] by adding a new section 506(g), which defines the categories of products considered to be regenerative medicine therapies. As further described by FDA [1], regenerative medicine therapies are considered to include cell therapies, therapeutic tissue engineering products, human cell and tissue products, and combination products using any such therapies, as well as gene therapies, including genetically modified cells that lead to a durable modification of cells or tissues. The development and approval of regenerative medicine therapies are regulated by FDA's Office of Tissues and Advanced Therapies (OTAT) in the Center for Biologics Evaluation and Research (CBER). In this review article, we present practical considerations for investigating regenerative medicine therapies intended for the treatment of rare diseases. The material presented may be useful to researchers who are undertaking the challenging task of finding and delivering new treatments for those in need.

Project description:BackgroundSince the cornea is responsible for transmitting and focusing light into the eye, injury or pathology affecting any layer of the cornea can cause a detrimental effect on visual acuity. Aging is also a reason for corneal degeneration. Depending on the level of the injury, conservative therapies and donor tissue transplantation are the most common treatments for corneal diseases. Not only is there a lack of donor tissue and risk of infection/rejection, but the inherent ability of corneal cells and layers to regenerate has led to research in regenerative approaches and treatments.MethodsIn this review, we first discussed the anatomy of the cornea and the required properties for reconstructing layers of the cornea. Regenerative approaches are divided into two main categories; using direct cell/growth factor delivery or using scaffold-based cell delivery. It is expected delivered cells migrate and integrate into the host tissue and restore its structure and function to restore vision. Growth factor delivery also has shown promising results for corneal surface regeneration. Scaffold-based approaches are categorized based on the type of scaffold, since it has a significant impact on the efficiency of regeneration, into the hydrogel and non-hydrogel based scaffolds. Various types of cells, biomaterials, and techniques are well covered.ResultsThe most important characteristics to be considered for biomaterials in corneal regeneration are suitable mechanical properties, biocompatibility, biodegradability, and transparency. Moreover, a curved shape structure and spatial arrangement of the fibrils have been shown to mimic the corneal extracellular matrix for cells and enhance cell differentiation.ConclusionTissue engineering and regenerative medicine approaches showed to have promising outcomes for corneal regeneration. However, besides proper mechanical and optical properties, other factors such as appropriate sterilization method, storage, shelf life and etc. should be taken into account in order to develop an engineered cornea for clinical trials.

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Regenerative medicine of pancreatic islets.

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Regenerative medicine of pancreatic islets.

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