Science Dialogue. By: Dr. Ahmed Hegab, PhD Dr. Hiroshi Kubo, MD, PhD. Hachinohe-Kita High School

Transcription

1 Science Dialogue at Hachinohe-Kita High School By: Dr. Ahmed Hegab, PhD Dr. Hiroshi Kubo, MD, PhD Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine

2 Topics of today s talk: 1- Stem cells and its potential in treating many diseases 2- My related experiments 3- Egypt

3 1- Stem cells and its potential in treating many diseases People are told stem-cell research holds great promise for the curing of many debilitating and life-threatening diseases as Parkinson's and Alzheimer's. But how? -what are stem cells? -Where do they come from -How do scientists think they can help improve medical treatments? See video 1

4 A stem cell is one that: can transform into virtually any human cell found in the body. has undifferentiated phenotype Self-renewal and proliferative capacity

5 -To understand the origin of stem cells, a review of human development is necessary. -Human life is created when an ovum is fertilized by a sperm. -When joined, they create a single-cell organism. - -This cell divides and divides eventually developing into a baby. See video 2

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7 Types of Stem Cells

8 - Because pluripotent and multipotent stem cells eventually develop into nearly all the cells in human body, scientists think they have great medical-treatment applications. - Through various experiments with animals, scientists have shown they can direct the specialization of stem cells. In other words, the cells can be manipulated into virtually any specialized cell. See video 3

9 Is there any success achieved? A lot of important information had been learned about: human development, origin of diseases and genetic diseases. BUT, no stem cell-based approved treatment is available yet. Although stem cells had been shown to differentiate in dishes into various types of cells, no complete or functioning tissue or organ have been produced (yet). On the other hand, there are still a lot of On the other hand, there are still a lot of problems:

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11 Ethical problems Using embryos from in-vitro fertilization clinics to obtain stem cells destroys the embryo and is considered by many people as a murder. In many religions, it will be considered as interfering with the well and creation of God which is forbidden.

12 Ethical problems-2 - Others counter that the embryos were destined to be destroyed anyway, since they are "leftovers" from a couple's efforts to become pregnant. -The potential benefits from the research outweighs any moral objections to destroying leftover embryos. -Besides, some argue, the embryo is only the potential for human life and is not actual human yet.

13 Adult stem cells see video 4 Merits: They are undifferentiated cells found throughout the body that divide to replenish dying cells and regenerate damaged tissues. The production of adult stem cells does not require the destruction of an embryo so it is more ethical. Less liable to produce auto immunity as they will be taken from the patient and given back to him after manipulation. Less liable to produce tumors.

14 Adult stem cells-2 Problems: They are rare We do not know where they exist (in which tissue and where inside that tissue) They are difficult to isolate and grow The good news are: They have been successfully isolated from many tissues including bone marrow, skin, GIT, brain, adipose tissue

15 2- My related experiments A) Search for adult stem cells in human lung B) Trying to regenerate damaged lung using HGF

16 A) Search for adult stem cells in human lung The lung must has a repair process and that is why it heals completely after several diseases like pneumonia and ARDS Patient with ARDS 6 months later

17 - The pulmonary system contains a variety of cell populations that each reside in distinct locations. - Basal, secretory,, and ciliated cells line the trachea and the proximal conducting airways. Columnar and clara cells lines the bronchioli and terminal bronchioli and alveolar type I and type II cells constitute the alveolar epithelium - Animal models of lung injury have suggested that epithelial stem cell populations exist in specific anatomical locations in the lung

18 In 2005, Carla Kim and Tylor Jacks from Massachusetts Institute of Technology described the first lung stem cell in mice. Since then many laboratories around the world are racing for finding its human equivalent.

19 My study protocol: In our laboratory, in addition to trying to reproduce the results of Karla Kim, I am trying to isolate human lung stem cells. I receive respected lung samples from surgery department and process it immediately. Using several digestive enzymes, I break the lung tissues into a suspension of single cells. Then, I stain them with different combinations of several stem cell markers. Then take them to a machine that can separate (sort) the desired cells according to their staining characteristics.

20 Because stem cells can t be cultured directly into a dish, I have to put it on a layer of fibroblasts that I have prepared from mouse embryos (Mouse Embryonic Fibroblasts or MEF). I culture these MEFs on special plates and add a liquid that contains nutrition and growth factors (called medium). To avoid confusion with the growing stem cells, MEF growth is arrested by radiation or medication so that any growing cell in the plate will be the one I have added.

21 Then keep the plates in a machine with special atmosphere called incubator and observe it every day under special microscope called inverted microscope. = If I could see cells growing and forming colonies, I will need to confirm if these are really stem cells or not by examining its characteristics and shape. = I already had several colonies that I believe it is stem cell colonies but the road is still long.

22 I need to isolate it, re-culture it several times and check for its ability to differentiate into various lung cell types before I can say that these are really: HUMAN LUNG ADULT STEM CELLS!

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24 B) Trying to regenerate damaged lung using HGF Emphysema is a disease of the lung characterized by chronic and progressive increase in the size of the air spaces, expansion of the alveoli and destruction of alveolar walls. It occurs mainly in smokers.

25 There is no medical cure for emphysema till now. The recent advances in the field of stem cells led us to think of using it to help treat these patients. Hepatocyte growth factor (HGF) is a growth factor that was discovered by a Japanese scientist. It was found to regenerate damaged liver. Later on, it was discovered that it also has the ability to regenerate many other tissues. It is also thought to mobilize stem cells and induce it to differentiate.

26 My study protocol: Make a model of emphysema in mice by giving them through the nose an enzyme that destroys their lungs giving a picture similar to human emphysema. Give some of them HGF for 1-4 weeks also through the nose and give nothing to some others. Kill all mice and test the effect of HGF on their lungs by examining by: 1- A machine that will measure their lung function 2- Microscope to see the shape of the lung and presence of tissue regeneration. Check the lung for genes and proteins that may be related to the mechanism of action of HGF to learn about how it works.

27 HGF caused marked improvement in lung emphysema! HGF effect may have been through stem cell mobilization and differentiation!

28 Another important result of our study is that HGF was successful when taken through the nose not by injection. Giving the lung medication through the nose is usually considered more safe than injection because it causes less side effects. Accordingly, we are planning to start soon giving HGF to human emphysema patients to see if it will improve their disease or not. If it worked, it will be the first curative treatment for emphysema ever!! Again.

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30 Thank you Dr. Ahmed Hegab