Stem cells :Basics &ethical issues

1. Stem cells :Basics &ethical issues Presented by Asmaa Mohamed Khalaf

2. بسم الله الرحمن الرحيم ﴿وَلَقَدْ خَلَقْنَا الْإِنْسَانَ مِنْ سُلَالَةٍ مِنْ طِينٍ. ثُمَّ جَعَلْنَاهُ نُطْفَةً فِي قَرَارٍ مَكِينٍ. ثُمَّ خَلَقْنَا النُّطْفَةَ عَلَقَةً فَخَلَقْنَا الْعَلَقَةَ مُضْغَةً فَخَلَقْنَا الْمُضْغَةَ عِظَامًا فَكَسَوْنَا الْعِظَامَ لَحْمًا ثُمَّ أَنْشَأْنَاهُ خَلْقًا آخَرَ فَتَبَارَكَ اللَّهُ أَحْسَنُ الْخَالِقِينَ﴾ المؤمنون: 12-14. صدق الله العظيم

3. Human development How a human develops from a fertilized egg into an embryo, and then a fetus. Some basics: 1-Fertilization(A male sperm and female egg fuse to form a zygote) (fertilised egg)-------( 0-24 hours). The zygote is totipotent: it can produce all the cell types needed to make a complete human.

4. . 2-Cleavage (The zygote divides into two identical cells). These cells then cleave and the process repeats to form a ball of around 100 cells( 1-4 days). -This happens while the zygote passes down the fallopian tube towards the uterus (womb).

5. . 3-Blastocyst formation (The ball of cells begins to specialize forming an outer layer of cells with a cluster of cells inside (inner cell mass) (5-14 days). -Cells of the inner cell mass are pluripotent: they can form all cell types of the human body except tissues which support the embryo, such as the placenta. -The inner cell mass is the source of one type of stem cell, embryonic stem cells.

6. . 4-Gastrulation (The cells in the inner cell mass move to form three layers, each of which will become different areas of the embryo).(Week3) -The 3 layers are the ectoderm, mesoderm and endoderm. -The first sign of the nervous system appearing (the primitive streak) occurs at gastrulation

7. . 5-Organogenesis (The formation of body organs). The embryo is called a fetus at 8 weeks when the structures which will give rise to all major organs are present.( Week 3-8) - The ectoderm forms the skin, brain and nervous system; the mesoderm forms muscle and the skeletal and circulatory systems and the endoderm forms the gut lining and many of the internal organs.

8. بسم الله الرحمن الرحيم ﴿يَا أَيُّهَا النَّاسُ إِنْ كُنْتُمْ فِي رَيْبٍ مِنَ الْبَعْثِ فَإِنَّا خَلَقْنَاكُمْ مِنْ تُرَابٍ ثُمَّ مِنْ نُطْفَةٍ ثُمَّ مِنْ عَلَقَةٍ ثُمَّ مِنْ مُضْغَةٍ مُخَلَّقَةٍ وَغَيْرِ مُخَلَّقَةٍ لِنُبَيِّنَ لَكُمْ وَنُقِرُّ فِي الْأَرْحَامِ مَا نَشَاءُ إِلَى أَجَلٍ مُسَمًّى ثُمَّ نُخْرِجُكُمْ طِفْلًا ثُمَّ لِتَبْلُغُوا أَشُدَّكُمْ وَمِنْكُمْ مَنْ يُتَوَفَّى وَمِنْكُمْ مَنْ يُرَدُّ إِلَى أَرْذَلِ الْعُمُرِ لِكَيْلَا يَعْلَمَ مِنْ بَعْدِ عِلْمٍ شَيْئًا﴾ الحج: 5 صدق الله العظيم

9. Definition of stem cell An unspecialized cell that has the ability to continuously divide and differentiate into various kind(s) of cells/tissues. Stem cells have two important characteristics. 1- They are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity.

10. . 2- Under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions (differentiation). -In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. -In other organs such as the pancreas and the heart, stem cells only divide under special conditions.

11. Why do scientists carry out research on stem cells? -In most cases our bodies use tissue stem cells to replace damaged or worn cells. However, where the damage is extensive, this repair mechanism can fail. -Also, many tissues in our body, for example brain tissue, cannot repair themselves efficiently. -Also many degenerative diseases are not yet treatable by modern medicine. -Transplantation of organs such as the heart can be an option, but it relies on a plentiful source of transplant organs, and many are in short supply. -So stem cell research has gained a lot of attention because it has the potential to fill this gap in human medical therapies.

12. Possible uses of stem cells 1-To provide lab-grown human or animal tissue for identifying new treatments for disease. 2-To produce new human tissue and organs to replace those lost in injury or disease. 3-To repair tissue by stimulating stem cells already in the body. 4-To use stem cells from patients with inherited genetic diseases to study how the disease develops. 5-To investigate human development to better understand diseases like cancer.

13. Stem cells in toxicology -Stem cells are an important new tool for developing unique, in vitro model systems to test drugs and chemicals and a potential to predict or anticipate toxicity in humans. -They can provide sufficient quantities of tissue specific human cells for screening or toxicity testing (models for cardiotoxicity, hepatotoxicity, genotoxicity). -They can provide human cell-based in vitro systems for safety evaluations to avoid failure in preclinical development of new therapeutic drugs, and to shift the focus of toxicology away from classical animal experiments .

14. History of Human Stem Cells -Stem cells have an interesting history that has been somewhat tainted with debate and controversy. -In the mid 1800, it was discovered that cells were basically the building blocks of life and that some cells had the ability to produce other cells. -In 1968, the first bone marrow transplant was successfully used in treatment of severe combined immunodeficiency. -Since the 1970, bone marrow transplants have been used for treatment of immunodeficiencies and leukemias.

15. . -In 1998, James Thomson (University of Wisconsin-Madison) isolated cells from the inner cell mass of the early embryo, and developed the first human embryonic stem cell lines. -In 1998, John Gearhart (Johns Hopkins University) derived human embryonic germ cells from cells in fetal gonadal tissue (primordial germ cells).

16. . -In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. ( Induced pluripotent stem cells). -In October 2010: Journal of Experimental Medicine that research shows tissues made from a person's stem cells could therefore be rejected, because mitochondrial genomes tend to accumulate mutations.

17. . -January 2012: The human clinical trial of treating type 1 diabetes using cord blood-derived stem cells achieved an improvement of C-peptide levels, reduced the median glycated hemoglobin A1C (HbA1c) values, and decreased the median daily dose of insulin in both human patient groups with and without residual beta cell function. Therapy appears "so simple and so safe"

18. Classification of stem cells 1-Stem cells can be classified based on their ability to differentiate into: A-Totipotent stem cells Each cell can form a complete organism (e.g., identical twins). They exist only in early embryos(1-3)days. B- Pluripotent stem cells They can generate all of the different cell types found in the body. They exist in the undifferentiated inner cell mass of the blastocyst(5-14)days. C- Multipotent stem cellscapable of producing many cell types but not all cell types in the body . They are derived from fetal tissue, cord blood and adult stem cells.

19. . 2-Scientists classified stem cells based on its source into three main types : (Embryonic stem cells, tissue stem cells and induced pluripotent stem cells). 1-Embryonic stem cells(pluripotent ). This type is obtained from early-stage embryos, specifically from the inner cell mass of the blastocyst .

20. . -Use of embryonic stem cells in research and therapy development: …Advantage Have a strong ability to self-renew (Telomerase ) in the laboratory, resulting in a constant supply of ES cells. …Disadvantages 1-Genetically different to cells of potential patients, so immune rejection could occur. 2-Ethical issues over embryo destruction .

21. . 2-Tissue stem cells ( adult stem cells) : -They are obtained .Directly from the organ or tissue in which they are found Such as bone marrow, blood, cornea, retina, intestine, muscle, nervous system, brain, and skin. • . Developing organs in the fetus, umbilical cord and placenta. -They are termed multipotent . For example, a brain stem cell can become any cell type of the brain, but not a muscle cell.

22. . -Their role in the body is to replace cells which die throughout life due to wear and tear or injury and disease. (stem cells in bone marrow replace blood cells). -They are ideal to use to investigate questions around cell differentiation that are specific to a certain tissue. -Although tissue stem cell ability to differentiate is more limited than pluripotent stem cells, they already have a track record of success in cell-based therapies.

23. . -Currently there are some effective treatments that use tissue stem cells from donors but these treatments carry a risk that donated cells will be rejected. -Use of tissue stem cells in research and therapy development: …Advantages 1-If taken from the patient’s own body for use in therapies, cells would be genetically identical to that of the patient, avoiding the problem of immune rejection. 2-There are less ethical considerations compared with using embryonic stem cells.

24. …Disadvantages 1-They usually produce only a limited number of different cell types. 2-Conditions supporting self-renewal in the laboratory have only been identified for a few tissue stem cell types, for instance skin and cornea. 3-Are found in very small numbers and are difficult to isolate. 4-Their numbers decrease with age.

25. . 3-Induced pluripotent stem cells (IPS.) -Somatic cells can be reprogrammed genetically to form pluripotent stem cells . -These IPS cell lines will have DNA matching that of the somatic cell donors and will be useful as disease models and potentially for allogenic transplantation. - This strategy will help researchers learn how to reprogram cells to repair damaged tissues in the human body.

26. Current sources of stem cells 1-Early embryos created by in vitro fertilization either .Those which are not needed for infertility treatment (Spare embryos) . Created specifically for research from donated eggs and sperm, using IVF methods or by activating donated human eggs without the use of sperm (parthenogenesis). 2-Early embryos created by somatic (body) cell nuclear transfer (SCNT), a procedure that bypasses the normal fertilization process by taking the genetic material from a cell in an adult’s body and fusing it with an empty egg cell.

27. . This is a form of therapeutic cloning, which would allow cells to be customized for each individual and thereby minimize the chances of tissue rejection. 3-Germ cells or organs of an aborted fetus. 4-Blood cells of the umbilical cord at the time of birth. 5-Some adult tissues (such as bone marrow). 6-Mature adult tissue cells reprogrammed to behave like stem cells. N.B In the UK, permission to create embryos for research is granted only for very specific reasons, for instance in cases where scientists are trying to use ES cells to study a particular inherited disease.

28. . • .

29. How embryonic stem cells are grown in the laboratory? -The generation of human ES cells has been controversial due to ethical issues concerning the status of the embryo. -Human embryonic stem cells aregenerated by transferringcells from a pre-implantation-stage embryointo a plastic laboratory culture dish that contains a nutrient broth known as culture medium. -The cells divide and spread over the surface of the dish.

30. . - In the original protocol, the inner surface of the culture dish was coated with mouse embryonic skin cellsspecially treated so they will not divide. -This coating layer (feeder layer) provide the cells a sticky surface to which they can attach and release nutrients into the culture medium. -Researchers have nowdevised ways to grow embryonic stem cells without mouse feeder cells.

31. . This is a significant scientific advance because of the risk that viruses or other macromolecules in the mouse cells may be transmitted to the human cells. -If these cells keep self-renewing for many months when grown in these conditions, and can still differentiate when tested, they are called a stem cell line. -Such cell lines can produce almost unlimited numbers of pluripotent ES cells for research.

32. Isolate inner cell mass (destroys embryo) Outer cells (forms placenta) Inner cells (forms fetus) Culture cells Day 5-14 Blastocyst “Special sauce”(largely unknown) Liver Heart repaired Kidney Heart muscle .

33. Stem Cell differentiation -Unspecialized stem cells give rise to specialized cells. -There are two types of signals inside and outside cells that trigger each step of the differentiation process. 1-The internal signals are controlled by a cell's genes, which are interspersed across long strands of DNA and carry coded instructions for all cellular structures and functions. 2- The external signals : Chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment. The interaction of signals during differentiation causes the cell's DNA to acquire epigenetic marks that restrict DNA expression in the cell and can be passed on through cell division.

34. How are embryonic stem cells stimulated to differentiate? -As long as the embryonic stem cells in culture are grown under appropriate conditions, they can remain undifferentiated (unspecialized). -But if cells are allowed to clump together to form embryoid bodies, they begin to differentiate spontaneously. It is a good indication of healthy culture but, it is not an efficient way to produce cultures of specific cell types.

35. . • -So, to generate cultures of specific types of differentiated cells scientists try to control the differentiation of embryonic stem cells. • 1- change the chemical composition of the culture medium. • 2-Alter the surface of the culture dish. • 3-Modify the cells by inserting specific genes.

36. . -If scientists can reliably direct the differentiation of embryonic stem cells ,they may be able to use the resulting differentiated cells to treat certain diseases in the future. -Research is underway to develop various sources for stem cells, and to apply stem cell treatments by transplanting cells generated from human embryonic stem cells for many diseases and conditions such as;

37. . • .

38. How are adult stem cells being used today? Stem cell procedures currently provide life-saving treatments for patients with leukemia, lymphoma, other blood disorders, and some solid tumors. The three main technologies in use today are: 1-Adult stem cell transplant: bone marrow stem cells -Stem cell technology has been used for more than 20 years in bone marrow transplants, where the patient's bone marrow stem cells are replaced with those from a healthy, matching donor. -If the transplant is successful, the stem cells will migrate into the patient's bone marrow and begin producing new, healthy leukocytes to replace the abnormal cells.

39. . -The method. -When stem cells are needed from a bone marrow donor, the aspiration procedure uses a special needle inserted into the bone (typically the femur or iliac crest) to collect the cells. - Although the procedure is uncomfortable it can be tolerated by both children and adults. -For stem cell transplants, aspiration will likely be done in several locations to ensure plenty of stem cells are available for the transplant.

40. . 2-Adult stem cell transplant: peripheral blood stem cells (PBSCs) -Easier to collect. -Obstacles. 1-Most blood stem cells reside in the bone marrow ,and a small number are present in the bloodstream. 2-PBSCs are sparse in the bloodstream, so collecting enough to perform a transplant can pose a challenge. 3-Time consuming One aphaeresis donation may take up to eight hours. Sometimes two donations are done on separate days, with each collection taking four to six hours.

41. . -So the donor receives the drug Filgrastim (neopogen) to move more stem cells from the bone marrow into the bloodstream. -Filgrastim is administered daily by injection for five days prior to collection. -The method Where the blood is drawn from the donor (similar to a blood donation), and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor.

42. . 3-Umbilical cord blood stem cell transplant: -Umbilical cords traditionally have been discarded as a by-product of the birth process. -In recent years, the stem-cell-rich blood found in the umbilical cord has proven useful in treating the same types of health problems as those treated using bone marrow stem cells and PBSCs. -Of all stem cell types, autologous harvesting involves the least risk.

43. Disadvantages of Stem cell treatments 1-May require immune-suppression because of a requirement for radiation before the transplant to remove the patient's previous cells, or because the patient's immune system may target the stem cells. 2-Pluripotency in the stem cells could also make it difficult to obtain a specific cell type. -Undifferentiated cells can create tissues other than desired types.

44. . 3-Some stem cells form tumors after transplantation; pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. 4-Unexpected behavior of the cells. 5- unknown long-term health effects.

45. قرارمجمع الفقه الإسلامي - (الدورة السابعة عشرة المنعقدة بمكة المكرمة في الفترة  من(19ـ23/10/1424هـ-2003) وبعدالاستماع إلى البحوث المقدمة في الموضوع وآراء الأعضاء والخبراء والمختصين ،والتعرف على هذا النوع من الخلايا ومصادرها وطرق الانتفاع منها ، اتخذ المجلسالقرار التالي): • أولاً /يجوز الحصول على الخلايا الجذعية وتنميتها واستخدامهابهدف العلاج أو لإجراء الأبحاث العلمية المباحة ، إذا كان مصدرها مباحاً ، ومن ذلكعلى سبيل المثال المصادر الآتية : 1-البالغون إذا أذنوا ، ولم يكن في ذلك ضرر عليهم . 2-الأطفال إذا أذن أولياؤهم لمصلحة شرعية وبدون ضرر عليهم . 3-المشيمة أو الحبل السري بإذن الوالدين . 4- الجنين السقط تلقائياً يجيزه الشرع، وبإذن الوالدين. 5. اللقائح الفائضة من مشاريع أطفال الأنابيب إذا وجدت وتبرع بها الوالدان مع التأكيد على أنه لا يجوز إستخدامها في حمل غير مشروع.

46. . • ثانيا /لا يجوز الحصول على الخلايا الجذعية وتنميتها واستخدامهابهدف العلاج أو الأبحاث العلمية ، إذا كان مصدرها محرم، ومن ذلكعلى سبيل المثال المصادر الآتية : 1. الجنين المسقط تعمُّداً بدون سبب طبي يجيزه الشرع . • 2. التلقيح المتعمد بين بويضة من متبرعة وحيوان منوي من متبرع. • 3. الاستنساخ العلاجي . - إسقاط الحمل- دون عذرشرعي -، هو محرَّم شرعاً، ويعد جناية تعاقب عليها الشريعة الإسلامية، لقوله سبحانه وتعالى :(ولا تقتلوا أولادكم خشية إملاق نحن نرزقهم وإياكم) الإسراء:31. فاستخدام الخلايا الجذعية التي تؤخذ من الجنين الآدمي، في أول 14 يوماً من تكونه، لا يكون إلا بعدإنشاء الجنين ثم تدميره (أي قتله)· فهو ينطبق عليه شرعاً، ما ينطبق على الإجهاضالإجرامي، الذي هو جريمة في حق الجنين البشري·

47. . - كما لا يجوز لأحدٍ التبرع بالنطف المذكرة والمؤنثة ، أو الحيوانات المنوية أو البويضات لإنتاج بويضات مخصبة تتحول بعد ذلك إلى " جنين " بهدف الحصول على الخلايا الجذعية منه . -والحكم ذاته في الحصول على هذه الخلايا بواسطة الاستنساخ العلاجي، فإن الإسلام يمنع انتهاك حرمة الجنين الآدمي، ولا يسمح بإجراء تجاربالاستنساخ البشري، ولو كان المبرر وجود الحاجة للتداوي والمعالجة لأمراض مستعصية أوخطيرة، فإنه يمنع شرعاً استنساخ الأجنّة للحصول على الخلايا الجذعية الجينية :(من قتل نفساً بغير نفس أو فساد فيالأرض فكأنما قتل الناس جميعاً( المائدة:32. - بينما ترى جمعية العلوم الطبية الإسلامية الأردنية جواز الحصول على الخلايا الجذعية بواسطة الاستنساخ العلاجي ويقيدون ذلك بضوابط وهي أن: 1- لا تُنقل الخلايا الجسدية إلى الرحم لأن ذلك يؤدي إلى الاستنساخ التكاثري . 2-أن لا يتم شراء البويضات البشرية حتى لا تُمتهن المرأة ولا تُستغل حاجتها إلى المال. (فالاستنساخ العلاجي مازال قضية خلافية )

48. ما هو الموقف الشرعي من أخذ اللقاحات الفائضة من مشاريع أطفال الأنابيب، وتنميتها للحصول على الخلايا الجذعية؟ -هناك تفاوت في حكم استخدام الفائض من أطفال الأنابيب : • حيث يؤيد مجلس المجمع الفقهي الإسلامي جواز تنمية اللقائح الفائضة من عمليات أطفال الأنابيب للحصول على الخلايا الجذعية وفق الضوابط الشرعية. • بينما ترى جمعية العلوم الطبية الإسلامية الأردنية أن ذلك لا يجوز، بل يجب عند إجراء التخصيب أن يقتصر على العدد المطلوب الذي سينقل إلى الرحم . • كما منعت اللجنة الوطنية للأخلاقيات الحيوية والطبية بالمملكة العربية السعودية استخدام البويضات الملقحة لاستخلاص الخلايا الجذعية في البحوث العلمية و رغم أن موقف اللجنة لم يكن بسبب مانع شرعي قطعي وإنما بُني على صعوبة ضبط وتقنين مثل هذه الأبحاث.

49. الضوابط الشرعية لجواز استخدام الخلايا الجذعية • إن السند الشرعي لمشروعية إجراءالأبحاث على الخلايا الجذعية و العلاج الجيني في الحالات الجائزة شرعا، هو المصلحة العلاجية للمرضى،وعدم الحد من التقدم العلمي في المجالات الطبية، ولكن ذلك مشروط بان يكون وفق الضوابط الشرعية التالية: 1-أن تؤخذ كل الاحتياطات العلمية والتقنية والفنيةوالمعملية الاحترازية لتفادي كل الأضرارالتي يمكن أن تترتب على العلاج الجيني. 2- أنتكون المنافع المتوخاة من العلاج محققة في حدود الظن الغالب، أما إذا كانت آثارهالإيجابية مشكوكا فيها فلا يجوز إجراؤه على الإنسان. 3-إن يكون العلاج فيحدود الأغراض الشريفة وبعيدا عن العبث والفوضى، وذلك بأن لا يكون لأجل إثبات قوةالعلم فقط دون أن يترتب عليه منافع للبشرية . 4-الا يكون العلاج الجيني في مجالالتأثير على السلالة البشرية وعلى فطرة الإنسان السليمة شكلاً وموضوعا (إي لا يؤديإلى تغيير خلق الله). 5-أن لا يؤدي العلاج إلى الإضرار بالبيئة أو إلى تعذيب الحيوان .

50. . • وعلىالعلماء، مراعاة هذه الضوابط الأخلاقية والدينية،و ضرورة البحث في البدائل الممكنة فيهذه المجالات، ومنها: • استخدام الخلايا الجذعية البالغة ،وإعادة برمجة الخلايا البالغة، واستخلاص الخلايا الجذعيةالبالغة من الأعضاء المهمة، والزراعة الذاتية لعضلات القلب، والاستفادة من الخلاياالجذعية من الحبل السري، وغيرها مما يدخل في إطار التداوي المشروع . • وفي الختام لا بد أن يتلازم مع البعد الأخلاقي والديني من خلال الضوابط المذكورةبعد تشريعي قانوني ,يكون فيه الردع والزجر لكل من يحاول تجاوز البعد الأخلاقي والديني ,فان الله يردع بالسلطان ما لا يردع بالقرآن.