Stem Cells - Diabetes Research Connection

Diabetes Research News
March 6, 2020

Scientists Found a Way to Generate Insulin-Producing Beta Cells

More than one million people in the United States are living with type 1 diabetes according to statistics from the Centers for Disease Control and Prevention. There is a strong push to improve management of the disease and find a cure. The more researchers learn about T1D, the more precise their prevention and treatment methods become.

A recent study reveals that improvements in stem cell therapy have reversed T1D in mice for at least nine months and, in some cases, for more than a year. One of the challenges that scientists have faced with using human pluripotent stem cells (hPSCs) is that it can be difficult to zero differentiation in one specific type of cell. Often multiple types of pancreatic cells are produced. While there may be an abundance of cells that scientists want, the infiltration of excess cells that are not needed diminishes their impact (even though they are not harmful).

Scientists at the Washington University School of Medicine in St. Louis have found a way to generate insulin-producing beta cells without creating as many irrelevant cells. Their approach focuses on the cell’s cytoskeleton, which is its inner framework. Through this process, they were able to produce vast amounts of beta cells that are able to normalize blood glucose levels.

When transplanted into severely diabetic mice (blood glucose levels above 500 mg/dL), the cells effectively reversed the effects of diabetes and brought blood sugar levels down into target range within two weeks. Normoglycemia was maintained for at least nine months.

This is a major step forward in stem cell therapy and the use of hPSCs to potentially cure diabetes one day. There is still more testing and research that needs to be done before this approach is applied to human trials.

Ongoing research is essential for finding a cure for T1D. Diabetes Research Connection supports these efforts by providing critical funding to early-career scientists pursuing novel research studies on the disease. By giving them the means to complete their projects, these researchers can continue to advance knowledge and treatment options. Learn more about current studies and how to help by visiting https://diabetesresearchconnection.org.

Learn More +

Diabetes Research News
October 17, 2019

Could Improving Cell-to-Cell Communication Enhance Cell Replacement Therapy Options for Type 1 Diabetes?

Researchers have been exploring the potential of stem cell therapies for years, however this is a very challenging endeavor because there are many factors that influence cell development, differentiation, and fate. In the case of type 1 diabetes, researchers have been studying methods for preventing the destruction of insulin-producing beta cells, stimulating the generation of new cells, and directing differentiation of stem cells among other strategies.

In a recent study, scientists focused on enhancing cell-to-cell communication in order to influence differentiation of embryonic stem cells. They examined the role of Connexin 43 (Cx43) specifically, which is a gap junction (GJ) channel protein. Scientists found that by using the AAP10 peptide to activate Cx43 GJ channels, they could steer differentiation of cells toward definitive endoderm and primitive gut tube lineages. In turn, with improved communication between cells triggered by the AAP10 peptide, definitive endoderm cells were more likely to become pancreatic progenitors and pancreatic endocrine progenitors.

Pancreatic progenitors (PP) and pancreatic endocrine progenitors (PE) play a role in the development of pancreatic islet cells which produce insulin and glucagon. These are the same cells that the body mistakenly attacks and destroys in individuals with type 1 diabetes. The ability to influence the differentiation of human embryonic stem cells into PPs and PEs may support improved cell replacement therapies for diabetes.

There is still a great deal of research to be done as it is difficult to manipulate the mechanisms of cell communication in order to produce desired results. Scientists are also continuing to investigate whether improved intercellular communication could lead to an increased production of pancreatic islet cells.

Researchers involved in this study include Dr. Wendy Yang, Dr. Laura Crisa, and Dr. Vincenzo Cirulli. Yang’s research is funded by Diabetes Research Connection (DRC) and Crisa and Cirulli are part of the DRC’s scientific review committee. To learn more about the DRC and the funding it provides to support type 1 diabetes research, visit http://diabetesresearchconnection.org.

Learn More +

Diabetes Research News
December 14, 2016

Economic 3D-Printing Approach for Transplantation of Human Stem Cell-Derived β-Like Cells

Original article published by IOP Science on December 1, 2016. Click here to read the original article.

Abstract

Transplantation of human pluripotent stem cells (hPSC) differentiated into insulin-producing βcells is a regenerative medicine approach being investigated for diabetes cell replacement therapy. This report presents a multifaceted transplantation strategy that combines differentiation into stem cell-derived β (SC-β) cells with 3D printing. By modulating the parameters of a low-cost 3D printer, we created a macroporous device composed of polylactic acid (PLA) that houses SC-β cell clusters within a degradable fibrin gel. Using finite element modeling of cellular oxygen diffusion-consumption and an in vitro culture system that allows for culture of devices at physiological oxygen levels, we identified cluster sizes that avoid severe hypoxia within 3D-printed devices and developed a microwell-based technique for resizing clusters within this range. Upon transplantation into mice, SC-β cell-embedded 3D-printed devices function for 12 weeks, are retrievable, and maintain structural integrity. Here, we demonstrate a novel 3D-printing approach that advances the use of differentiated hPSC for regenerative medicine applications and serves as a platform for future transplantation strategies.

[su_button url=”http://iopscience.iop.org/article/10.1088/1758-5090/9/1/015002/meta?elqTrackId=96062d779f46499eb7cc18d9ab30d665&elq=3d599e01edda49df92afa531a8a717ae&elqaid=17717&elqat=1&elqCampaignId=10609″ target=”blank” style=”flat” background=”#64b243″ size=”6″ center=”yes” radius=”5″ icon=”icon: angle-right”]Continue Reading[/su_button]

Learn More +

Diabetes Research News
February 19, 2015

Protein That Repels Immune Cells Protects Transplanted Pancreatic Islets From Rejection

Transplanting islets encapsulated with CXCL12 restores blood sugar control without immunosuppression in animal models of diabetes

An approach developed by Massachusetts General Hospital (MGH) investigators may provide a solution to the limitations that have kept pancreatic islet transplantation from meeting its promise as a cure for type 1 diabetes. In the March issue of the American Journal of Transplantation, the research team reports that encapsulating insulin-producing islets in gel capsules infused with a protein that repels key immune cells protected islets from attack by the recipient’s immune system without the need for immunosuppressive drugs, restoring long-term blood sugar control in mouse models. The technique was effective both for islets from unrelated mice and for islets harvested from pigs.

“Protecting donor islets from the recipient’s immune system is the next big hurdle toward making islet transplantation a true cure for type 1 diabetes,” says Mark Poznansky, MD, PhD, director of the MGH Vaccine and Immunotherapy Center, who led the study. “The first was generating enough insulin-producing islets, which has been addressed by several groups using pig islets or – as announced last fall by Doug Melton’s team at the Harvard Stem Cell Institute – with islet cells derived from human stem cells. Now our technology provides a way to protect islets or other stem-cell-derived insulin-producing cells from being destroyed as soon as they are implanted into a diabetic individual without the need for high-intensity immunosuppression, which has its own serious side effects.”

While transplantation of pancreatic islets has been investigated for several decades as a treatment and potential cure for type 1 diabetes, its success has been limited. Along with the risk of rejection that accompanies all organ transplants – a risk that is even greater for cross-species transplants – donated islets are subject to the same autoimmune damage that produced diabetes in the first place. The immunosuppressive drugs used to prevent organ rejection significantly increase the risk of infections and some cancers, and they also can contribute directly to damaging the islets. Among the strategies investigated to protect transplanted islets are enclosing them in gel capsules and manipulating the immune environment around the implant. The MGH-developed approach includes aspects of both approaches.

Previous research from the MGH team demonstrated that elevated expression of a chemokine – a protein that induces the movement of other cells – called CXCL12 repels the effector T cells responsible for the rejection of foreign tissue while attracting and retaining regulatory T cells that suppress the immune response. For the current study they investigated how either coating islets with CXCL12 or enclosing them in CXCL12 gel capsules would protect islets transplanted into several different mouse models.

Their experiments revealed that islets from nondiabetic mice, either coated with CXCL12 or encapsulated in a CXCL12-containing gel, survived and restored long-term blood sugar control after transplantation into mice with diabetes that was either genetically determined or experimentally induced. CXCL12-encapsulated islets were even protected against rejection by recipient animals previously exposed to tissue genetically identical to that of the donor, which usually would sensitize the immune system against donor tissue. CXCL12-encapsulated pig islets successfully restored blood sugar control in diabetic mice without being rejected. The ability of CXCL12 – either as a coating or encapsulating gel – to repel effector T cells and attract regulatory T cells was also confirmed.

“While studying this procedure in larger animals is an essential next step, which is currently underway with the support of the Juvenile Diabetes Research Foundation, we expect that this relatively simple procedure could be readily translatable into clinical practice when combined with technologies such as stem-cell-derived islets or other insulin-producing cells and advanced encapsulation devices,” says Poznansky, an associate professor of Medicine at Harvard Medical School. “We also hope that CXCL12 will have a role in protecting other transplanted organs, tissues and cells as well as implantable devices, a possibility we are actively investigating.”

http://www.medicalnewstoday.com/releases/289590.php?tw

Learn More +

Diabetes Research News
October 22, 2014

Type 1 Diabetes Discovery: Stem Cells Make Millions of Human Insulin Cells

As we are all aware, type 1 diabetes is an autoimmune disease where the body destroys insulin-producing beta cells in the pancreas. Without insulin, the body cannot control glucose, which can lead to high levels of blood sugar that eventually damage tissues and organs. A new study exposes how scientists successfully created billions of insulin-producing pancreatic beta cells from embryonic stem cells.(1)

The Harvard stem cell researchers report how they transplanted the stem cell-derived beta cells into the kidney of a diabetic mouse that showed no signs of the disease after two weeks. The study is a huge advance for patients with type 1 diabetes, and some with type 2 diabetes, many who require daily injections of insulin.

For their new technique to work in people with type 1 diabetes, the researchers must create a mechanism that halts a recipient’s immune system from attacking and destroying the 150 million or so beta cells they would receive. The team is currently collaborating with colleagues at the Massachusetts Institute of Technology (MIT) to develop an implant that protects the stem cell-derived beta cells from immune attack.

With human embryonic stem cells as a starting point, the scientists were able to produce, in the massive quantities needed for cell transplantation and pharmaceutical purposes, human insulin-producing beta cells that are equivalent in almost every way to normally functioning beta cells.(3) This is the first time this has been done.

The stem-cell-derived beta cells are currently undergoing trials in animal models, including non-human primates. Researchers have attempted to generate human pancreatic beta cells that could be cultured under conditions where they produce insulin. Cell transplantation as a treatment for diabetes is still experimental, using cells from cadavers, requiring the use of powerful immunosuppressive drugs, and having been available to only a small number of patients.

Richard A. Insel, chief scientific officer of JDRF, formerly known as the Juvenile Diabetes Research Foundation, said, “JDRF is thrilled with this advancement toward large-scale production of mature, functional human beta cells by Dr. Melton and his team. This significant accomplishment has the potential to serve as a cell source for islet replacement in people with type 1 diabetes, and may provide a resource for discovery of beta-cell therapies that promote survival or regeneration of beta cells and development of screening biomarkers to monitor beta cell health and survival to guide therapeutic strategies for all stages of the disease.”(4)

The work was funded by the Juvenile Diabetes Research Foundation, the Harvard Stem Cell Institute, the National Institutes of Health, the JPB Foundation, and Mike and Amy Barry.(4)