Novel Therapeutics: Cell Therapy after Transplantation

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Del curso dictado por Universiteit Leiden

Clinical Kidney, Pancreas and Islet Transplantation

188 calificaciones

Universiteit Leiden

Clinical Kidney, Pancreas and Islet Transplantation

188 calificaciones

Kidney transplantation is a major advance of modern medicine which provides high-quality of life for patients with end-stage renal disease. What used to be an experimental, risky, and very limited treatment option more than 50 years ago is now routinely performed in many countries worldwide. The number of renal transplants is expected to rise sharply in the next decade since the proportion of patients with end stage renal disease is increasing. Are you interested in clinical kidney, pancreas and islet transplantation? If you are a (bio) medical student or a health care professional who works in the (pre) clinical transplant field this might be the course for you. This course is also for anyone interested in the research and knowledge on clinical transplantation. The course will be taught by a multidisciplinary team of transplant professionals and will give you the state of the art updates. It is divided in 4 modules: 1) Before the transplant 2) The surgical procedures and the challenged patient, including the patient with diabetes 3) Early challenges 4) Late challenges after transplantation. The offered modules will include lectures, interactive patient cases, 3D movies, interviews with well-known experts and with patients and a donor, a serious game to increase knowledge of the field and of course an active forum. Become an expert and join us! The course is endorsed by The European Society of Organ Transplantation (ESOT), The International Society of Nephrology (ISN) and The Transplantation Society (TTS). This MOOC has been accredited for Continuing Medical Education (CME). Health care professionals who works in the (pre) clinical transplant field, other health care professionals and general practitioners can obtain CME credit at 'LUMC-Boerhaave CME' upon passing the course. For more information we like to refer to the "Additional introduction for obtaining CME credit" module in week 1 of the course For another interesting course on organ donation and transplantation, see Organ Donation: From Death to Life from Cape Town University https://www.coursera.org/learn/organ-donation

De la lección

Early Challenges in Transplantation

You are now familiar with the basic knowledge about challenges in transplant recipients and the surgical transplant procedures. Once the transplantation has been successful, it doesn’t mean everything is stable. What are actually the graft survival data? Which challenges do we face in the first months? How can we tackle these challenges? 3D movies about early surgical challenges and about the targets for immunosuppressives, including cell therapy, will help you to understand the concepts. In addition, we invite you to master the advanced knowledge and to give your opinion in the patient cases in the forum. There is also a serious game about a patient case. Can you solve the challenges? And can you think of a scenario for the game and help us with building? We will make a game of the best scenario, which will be incorporated in the course. In the honors lesson you can learn in more detail about immunological concepts, including the complement system. A patient case will help to show you the importance of this knowledge. Good luck with this module and happy learning!

Immune Suppression10:56

Novel Therapeutics: Cell Therapy after Transplantation8:12

Conoce a los instructores

Marlies Reinders
Dr.
LUMC, Department of Nephrology and Transplantation
Frans Claas
Professor
LUMC, Department of Immunohaematology and Blood Transfusion
Cees van Kooten
Professor
LUMC, Department of Nephrology and Transplantation
Sebastiaan Heidt
Dr.
LUMC, Department of Immunohaematology and Blood Transfusion
Volkert Huurman
Dr.
LUMC, Department of Transplant Surgery
Hans de Fijter
Professor
LUMC, Department of Nephrology and Transplantation
Eelco de Koning
Professor
LUMC, Department of Nephrology and Transplantation and Endocrinology and Metabolism
Andre Baranski
Dr.
LUMC, Department of Transplant Surgery
Ton Rabelink
Professor
LUMC, Department of Nephrology and Transplantation
Aiko de Vries
Dr.
LUMC, Department of Nephrology and Transplantation
Jan Nico Bouwes Bavinck
Dr.
LUMC, Department of Dermatology
Leo Visser
Professor
LUMC, Department of Infectious Diseases
Ingeborg Bajema
Dr.
LUMC, Department of Pathology

Hi there.

So in this lecture, we will focus on novel treatment options for

the transplant recipient.

Namely cellular therapy.

These include various cells.

Including mesenchymal stromal cells, also called MSCs, and regulatory T cells.

Since these cells are immunosuppressive and might have less side effects compared

to the current therapy, they are of interest in transplantation.

So in this lecture we have chosen to focus on MSCs.

In the lecture of tolerance you will get to know more about the regulatory T cells.

We will answer the following questions.

What are MSCs?

Why are they of interest in the transplant field?

And which steps are performed from isolation to infusion?

And what are the indications, initial results and lessons learned so far?

So, after this movie, you will be able to answer these questions.

MSCs of interest in various clinical protocols in transplantation,

with the aim to induce tolerance, to prolong allograft survival,

to inhibit and treat rejection, and to minimize fibrosis.

Moreover, they can be used in protocols with minimization

of the other toxic medications.

First clinical studies are now starting to test these indications,

after safety and feasibility has been tested.

So let's now look at the movie,

the whole process from isolation through infusion and follow up will be described.

MSCs are an interesting candidate in the transplant recipient due to

their immune suppressive and reparative properties.

MSCs can

be isolated from the bone marrow from the iliac crest through bone marrow aspiration.

The bone marrow contains mainly hematopoietic cells which have

been used to treat severe diseases of the bone marrow, including leukemia.

These cells have also been used in clinical protocols after transplantation

with the aim to induce tolerance of the transplanted organ.

The bone marrow also contains a small fraction of primary MSCs,

making the amplification of MSCs ex vivo necessary.

Criteria that identify MSCs are, their adherence to plastic in

standard culture conditions.

Their differentiation capacity in cartilage,

adipose tissue,

and bone

and their phenotype.

Besides the bone marrow, MSCs can easily be isolated from fat tissue.

In addition, they can be isolated from virtually all organs,

including the kidney, which is of interest for renal repair.

Why are MSCs of interest after transplantation?

MSC's have important effects on various players of the innate and

adaptive immune system.

Including macrophages, DC's, T-cells and

B-cells, via the production of immune modulating factors

including IDO, PGE2, IL-10 and

HLA-G. MSCs also inhibit fibrosis

by releasing various vectors including HGF and BMP-7.

MSCs have direct effects on the endothelium by enhancing angiogenesis

via various angiogenic factors including VEGF and angiopoeitins.

All these effects by MSCs could be of major importance for

repair of the transplanted kidney.

The amplification of MSCs should be performed under strict

good manufacturing practice conditions.

After the isolation, MSCs are cultured and expended through different steps.

First, mononuclear cells are isolated from the bone marrow

using density gradient separation.

Then the mononuclear cells are cultured

using an optimal combination of growth factors and cytokines.

Through plastic adherence, MSCs are selected.

To obtain enough cells,

the culture and expansion process will take about four weeks.

Before MSCs are released, several quality tests are performed,

which include service marker expression, absence of microbial contamination.

Spindle shaped morphology, colorless cell suspension devoid of cell aggregates.

No genetic abnormalities, and viability.

Awaiting the results of the quality tests, and

to make infusion of MSC a later time point possible, MCSs are frozen.

To maintain cell viability control rate freezing is used

with a guided temperature profile.

After this controlled procedure,

MSCs are stored in vapor phase nitrogen until their use.

The source can be autologous from the patient itself,

or allogeneic from a third party donor

or from the kidney donor.

Most protocols in renal transplantation use autologous MSCs.

Allogeneic MSCs are also of interest,

since these cells can be taken off the shelf at any moment.

However, these cells from another donor might induce immunization of the patient.

Therefore, HLA selection criteria are advised.

MSCs are infused in a patient via intravenous infusion.

Follow up studies during the outpatient clinics include determination

of safety and feasibility, lab and urinary markers for renal function,

histology, immune monitoring, and measurement of biomarkers.

Of importance follow up should not only be performed in the short term, but

also on the long term.

So are you able to explain the different steps of MSC isolation to treatment

after seeing this movie?

Let's look at the important lessons.

So first of all, MSCs are of interest for

transplantation due to immunosuppressive and reparative properties.

Second, the process from isolation through administration is complex.

And third indications include treatment of rejection,

induction of tolerance and prevention of fibrosis.

And fourth, close follow up of the treated patients is of major importance.

There are still many questions which should be investigated the coming

years regarding cell therapy.

There is optional literature on this subject so

I invite to discuss the challenges online.

What do you think are the major challenges and can you come up with solutions?

In the fourth module in the interview with Professor Wood about tolerance,

you will learn more about the regulatory T cells.

Years of research in her lab have now led to one of the first clinical trials of

regulatory T cells into human transplantation.

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