Stem Cell Based Therapy of Diabetes - Part 2, by Professor Ole Dragsbæk Madsen

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En provenance du cours de University of Copenhagen

Diabetes - a Global Challenge

344 notes

University of Copenhagen

Diabetes - a Global Challenge

344 notes

Diabetes and obesity are growing health problems in rich and poor countries alike. With this course you will get updated on cutting-edge diabetes and obesity research including biological, genetic and clinical aspects as well as prevention and epidemiology of diabetes and obesity. All lectures are provided by high-profile scientists from one the world's leading universities in diabetes research. This course is part of the EIT Health Campus programme. We hope you will enjoy our course. Best Wishes Jens Juul Holst, Signe Sørensen Torekov and Nicolai Wewer Albrechtsen Department of Biomedical Sciences Novo Nordisk Foundation Center for Basic Metabolic Research Faculty of Health and Medical Sciences University of Copenhagen

À partir de la leçon

Stem Cell Based Therapy of Diabetes

Module 10 will focus on 'Stem Cell Based Therapy of Diabetes' and the question 'What are the advantages and disadvantages in cell therapy of diabetes?' is raised by Professor Ole Dragsbæk-Madsen.

Stem Cell Based Therapy of Diabetes - Part 1, by Professor Ole Dragsbæk Madsen13:24

Stem Cell Based Therapy of Diabetes - Part 2, by Professor Ole Dragsbæk Madsen9:29

Stem Cell Based Therapy of Diabetes - Part 3, by Professor Ole Dragsbæk Madsen25:32

Rencontrer les enseignants

Jens Juul Holst
Professor, MD, DMSc
Department of Biomedical Sciences & NNF Center for Basic Metabolic Research
Signe Sørensen Torekov
Associate Professor, MSc, PhD
Department of Biomedical Sciences & NNF Center for Basic Metabolic Research
Nicolai Jacob Wewer Albrechtsen
MD, GCSRT, PhD student
Department of Biomedical Sciences & NNF Center for Basic Metabolic Research

[MUSIC].

The Edmonton protocol was published back in year 2000 by the

team of scientists led by James Shapiro from University of Edmonton.

And the major breakthrough that they actually published at that time was

that you could normalize blood glucose without insulin injections.

And the first study was published, including seven patients

that were treated with islet transplantation from organ donors.

So the focus is cell replacement and organ donation of islet of langerhans.

As illustrated, you isolate only the islets of langerhans out of the

big organ of the pancreas and then you simply inject, or infuse

the islet cells into the portal vein of the recipient where the

islets become trapped in the calip eh, capillary system of the liver.

And they will start to resume their ability to sense the glucose and secrete

adequate amounts of insulin to sustain glycemia at normal levels.

[BLANK_AUDIO]

The major breakthrough by the Edmonton group was that these

seven patients all came off insulin for the initial period.

And remember, they were continuously receiving immunosuppression

to prevent rejection or destruction of the donor islet cells.

The patient group enrolled in such studies are representing the most severe form of

type one diabetes, also eh, at least

in the United States, called brittle diabetes.

And it is almost impossible to control

their diabetes adequately by conventional insulin injections.

They have recurrent hypoglycemic episodes.

And hypoglycemia is identified as probably one of the worst experiences by a patient.

And it's due to over insulinization.

Furthermore the also have no detectable C-peptide levels.

And C-peptide is a split product of pro-insulin that

indicates that whenever insulin is secreted, C-peptide is also secreted.

So, C-peptide lack of C-peptide means that there

is no endogenous beta-cell left in these patients.

Therefore, these patients have a very high risk of developing complications.

The patients actually receive multiple islet donor infusions, at least two

up to three and they received a glucocorticoid-free immunosuppression,

part of the explaining the success of the first publication.

The diagram at the left shows the wide range of glucose fluctuations

before the transplantation, which is typical for this group of diabetics.

Strikingly after the transplant, these fluctuations are narrowed again down

to actually be within the normal range of non-diabetic people.

Indicating, and this is again indicated by the horizontal lines stipulated

lines that indicate the normal area of again, black oscillated hemoglobin A1C.

So this is in fact taken as a proof of concept

that cell replacement therapy can really work in type one diabetes.

So if you can protect against the immune destruction, and you can repeat, replace

the missing beta cells, you can actually

restore a normal glucose regulation in the blood.

As mentioned, the most severe experience for diabetics

not only the brittle, but many diabet, most type one diabetics and also type two,

is when you receive too much insulin, the

blood sugar drops down to dangerously low levels.

As I mentioned, called hypoglycemia, in

contrast to hyperglycemia, which is diabetes.

And hypoglycemia is a situation where the glucose

is so low that the brain cannot function.

It is equivalent to shutting off the battery of a computer.

It stops functioning, and it is actually a lethal condition for the

brain if it's prolonged, and it may result in coma and death.

Fortunately, most diabetic patients can actually feel

when they are approaching the dangerous situation.

But those who lose this ability called the

suffering of hypoglycemia unawareness, are highly vulnerable to increases

in their severe hypoglycemic episodes, and they are

also at the deterioration of their quality of life.

It is likely the strongest force preventing

diabetic patients to comply with an optimal insulin

injection regimen to control their blood, their

blood glucose in, in the most optimal fashion.

to, which is required to prevent complications.

And, and this experience when you get the hypoglycemic

episodes, actually is a no go for many patients and

they would rather take less insulin, be less stringent with

their diabetes, have more hyperglycemia to avoid the hypo situation.

As I mentioned, the Edmonton Protocol propri, provides proof

of principle for cell therapy in type one diabetes.

And possibly, most importantly, it's,

it effectively protects against hypoglycemic episodes.

Thus, eliminating the biggest fear of diabetic patients.

The lower graph, in this panel,

is illustrating that actually after five years

follow-up following transplantation, there's only 7.5%

of patients that are still off insulin.

And they have not experienced hyperglycemia, nor hypoglycemia in this

period, and have thus remained normal in their blood glucose regulation.

The hemoglobin A1C is the left side of the curve

and it's a surrogate mark of a blood glucose regulation.

So the higher level, the higher spontaneous glycation

reactions you have in your blood, and that

is again directly related to the time of

exposure to high sugar levels in your blood.

So, the higher level of hemoglobin A1C you have in your body, the more indication

it is that you have in the past three months been exposed to high blood glucose.

So these patients, that have the lower curve,

is actually within the normal range of non-diabetic persons.

The middle curve represents a large group of patients, this is the curve with the

open circles, that are actually now back on

insulin in order to keep blood glucose regulation.

But they still have some C-peptides circulating

in their bodies, and this is a surrogate

marker that there are still grafted eyelet

cells surviving in their body from the transplantation.

There's just not enough functioning beta cells to sustain normal glycemia,

so they need to topped up, be topped up with insulin injections.

However, the most interesting aspect about this group

of patients is that despite the fact that

they are now back on insulin injections, they

are still cured for their previous dreadful recurrent hypoglycemia.

The curve is then the upper curve is then, the unfortunate group of patients

that have been able to fully reject and kill off all of the grafted cells.

So they have no further C-peptide secretion,

and they are fully back on previous insulin

dosing, and they are also actually as

poorly manageable as they were before the transplantation.

So in those patients, the therapy did not work.

But in conclusion, islet transplantation has greatly improved the quality for the

patients with severe type one diabetes

in those patients that retain functioning cells.

And this is by relieving the glucose instability and

problems with hypoglycemia, as long as the graft survives.

Furthermore, it has been suggested that the scarce availability of the organ donor

islets should rather be distributed among more patients, with the indications

to primarily prevent recurrent hypoglycemia, rather than achieving the

full independence of insulin injections.

[MUSIC]

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