Cell therapy of the immune system
Thymus cells derived from human embryonic cells,
stimulate the immune system of mice
LifeSciencesToday based on materials from the University of California, San Francisco:
UCSF Scientists Use Human Stem Cells to Generate Immune System in MiceScientists at the University of California, San Francisco (University of California, San Francisco) for the first time created a functional tissue of the human thymus from embryonic stem cells.
Transplanted into mice, this tissue stimulates the formation of white blood cells, which are necessary for the body to have a normal immune response and prevent pathological autoimmune reactions.
Colonies of undifferentiated human embryonic stem cells (ESCs) are rounded dense masses of cells. The flat elongated cells between them are fibroblasts used as a feeder layer for the growth of ESCs (photo: University of Wisconsin-Madison).Scientists who have received thymus cells that cause proliferation and maturation of functional immune cells during transplantation believe that this achievement marks an important step towards new potential stem cell-based therapies, organ transplantation, new therapies for type 1 diabetes and other autoimmune diseases, as well as immunodeficiency.
Starting with human embryonic stem cells, scientists led by immunologist Mark Anderson, MD, PhD, and director of the UCSF Diabetes Center Matthias Hebrok, PhD, used a unique combination of growth factors that determine the direction of cell development, and eventually found a technique that allowed to obtain a functional thymus tissue.
As reported in the online edition of the journal Cell Stem Cell (Parent et al., Generation of Functional Thymic Epithelium from Human Embryonic Stem Cells that Supports Host T Cell Development), the resulting tissue is able to support the growth and development of white blood cells, known as T cells. T cells are the main population of immune cells that respond to specific pathogens, as well as preventing the destruction of the body's own tissues by the immune system.
The thymus is a small gland located in the upper part of the breast under the sternum, but its small size does not detract from its role in the body: people with impaired thymus function die from infections at an early age.
Given the invasive nature of cell therapy, which remains only an experimental method so far, the results of transplantation of thymus tissue obtained in the laboratory are likely to be studied in patients with fatal diseases for which there are no effective treatments, says Dr. Anderson. One of these diseases may be Di Giorgi syndrome, in which children are born without a thymus gland and die in infancy.
However, this achievement may have an even deeper impact on tissue transplantation, the goal of the developing field of stem cell–based therapy. Currently, the use of these methods is limited by the property of the immune system to reject transplanted cells. For transplantation, stem cells can be directed simultaneously along two development trajectories to form both thymus tissue and the organ being transplanted. According to Dr. Anderson, transplantation of both could make it possible to overcome rejection without drug immunosuppression.
The thymus is the environment in which T cells mature and where they learn to distinguish "I" from "not-I". Some T-cells are prepared by the thymus for attacks on "foreign invaders", including transplants, while other T-cells attacking our own tissues are destroyed by the thymus.
Similarly, thymus tissue can be used in the future to "retrain" the immune system in autoimmune diseases.
A model of the production and maturation of thymic epithelial progenitors (thymic epithelial progenitors, TEPs) progenitors differentiated from human embryonic stem cells (hESCs) in the body of athymic nude mice (athymic nude mice).
(1) TEPs are derived from hESC in vitro using a specified combination of several factors.
(2) At the end of stage 4, TEPs are transplanted under the renal capsule of thymus-deficient naked mice, where in vivo maturation of TEPs into thymus epithelial cells (TECs) occurs.
(3) In the presence of hESCs-derived TECs, progenitor T cells of the host organism mature from CD4- CD8-DN T cells (white) into CD4+ CD8+ DP (green) and single positive (single positive, SP) T cells (blue and red).
(4) Functional T cells migrate to the periphery, where they mediate immune responses such as rejection of allogeneic skin grafts
(Fig. Cell Stem Cell).Scientists have discovered many proteins and growth factors that are active in the process of embryonic development and are of key importance for the formation of organs.
Dr. Helbrok has spent years trying to get insulin-secreting beta cells of the pancreas that die in diabetes.
Helbrok and other scientists were helped to orient themselves in the search for opportunities in managing the formation of various tissues by a number of "control points" – the consistent appearance of specific marker proteins during the development of cells in different organs of the gastrointestinal tract.
In order to "get close" to the thymus cells, the scientists followed dozens of protocols, each of which had its own time of inclusion of key factors. "If we had used one of the factors a day longer or shorter, it wouldn't have worked," Helbrok explains.
Scientists warn that they have not created a copy of the thymus: the protocol used in this study allowed only about 15 percent of embryonic stem cells to be differentiated into thymus cells. However, according to Dr. Anderson, "they have developed a tool that allows you to modulate the immune system in a way that has never been possible before."
Portal "Eternal youth" http://vechnayamolodost.ru20.05.2013