1. Cell Based Therapy For Diabetes
Nidal Younes, MBBSc, MA, TSES
Endocrine Surgeon

2. 2015/05/04 

3. Journal of cell

4. New hope in reversing Type 1 diabetes
UT18 to boost the activity of TLR4 in mice with symptoms of diabetes.
The Enquirer12:16 a.m. EDT June 15, 2014
University of Cincinnati researchers have found a way to reverse new-onset Type 1 diabetes in mice, a development that may advance combating the illness in humans.
The researchers, led by Dr. William Ridgway, targeted a specific part of the immune system to trigger the reversal.
Ridgway, a professor and director of the division of immunology, allergy and rheumatology at the UC College of Medicine, presented the study Saturday at the American Diabetes Association’s 74th Scientific Sessions in San Francisco.
أجسام مضادة من نوع UT18 تستهدف مستقبلات TLR4 لتحفيزها وبالتالي عكس تأثير السكري في نسبة كبيرة من الفئران الغير بدينة المصابة حديثاً بالمرض.

5. عملية في سوريا تشفى امي و زوجي باذن الله على يد الطبيب محمد ربيع نجار
عملية في سوريا تشفى امي و زوجي باذن الله على يد الطبيب محمد ربيع نجار
 ازالة خلايا بين إصبعي الإبهام والسبابة ، وقد أكتشف في البداية أن هذه الخلايا هي خلايا ذات منشئ عصبي وقد أستأنف أبحاثه أكثر في مجال التكوين الهرموني لهذه العقد والخلايا بالاعتماد على مخبر الدكتور محمد داود( أخصائي تشريح نسيجي وهرموني في مدينة جبلة) وأطباء آخرين وأكتشف أنه تؤثر على الجملة العصبية للدماغ ، وتسبب منعكس عصبي على بعض أجهزة الجسم ، طبعاً إن إزالة أو تخريب أو تسكين هذه الخلايا والعقد تمنع هذه الانعكاسات التي تحصل في جسم الإنسان وتؤدي إلى تغيرات هرمونية و فيزيولوجية. هذا الموضوع وهذا البحث نال جائزة باسل الأسد 

6. كذبة الخلايا الجذعية البيت العربي
الخميس 3 شعبان 1436 هـ - 21 مايو 2015م - العدد , صفحة رقم ( 9 )
البيت العربي
كذبة الخلايا الجذعية
د. محمد ناهض القويز
    قبل فترة تمكن فريق من هارفارد إكثار الخلايا المفرزة للإنسولين من الخلايا الجذعية. وهذا بلا شك فتح كبير في الطب ولكنه لم يكتمل بعد إذ لابد من الوصول إلى الطريقة التي تحل فيها هذه الخلايا محل الخلايا المدمرة في بنكرياس المرضى المصابين بالسكر من النوع الأول. وقد أشار الفريق إلى أن ذلك قد يستغرق سنوات.
ولكن قفز إلى السطح مستشفيات وأطباء في دول تفتقد آلية حماية المرضى كالأردن وكرواتيا والهند وكوريا وغيرها تدعي أنها تعالج السكر وأمراضا أخرى بحقن الخلايا الجذعية.
وللأسف تم كالعادة التسويق لهم من خلال بعض المحطات الفضائية ووسائل التواصل الاجتماعي فانكب الخليجيون عموما والسعوديون بالذات على تلك العيادات وبدأنا نسمع كما هي الحال دائما أفرادا يدعون أنهم تحسنوا.
ويتطور الخبر إلى كرة ثلج من دون أن تحرك الجهات المعنية ساكنا للحد من هذه الادعاءات ولحماية المرضى وأموالهم من دجل الدجالين.
صورة تكررت كثيرا مع أدعياء المعالجة من عطارين وعشابين وحتى أطباء لم يحترموا أخلاقيات المهنة.
دورنا كمختصين أن نوضح للناس حقيقة الأمر حول هذا الادعاء وأن نعرض الحقائق وهي كما يلي:
بدأ استخدام الخلايا الجذعية في زراعة النخاع لعلاج سرطان الدم وهذا قديم جدا وليس صعبا لأنهم يحقنون خلايا جذعية سليمة مكان الخلايا الجذعية التي قتلوها بالكيماوي.
بعد سنوات من الأبحاث تمكن اليابانيون من تحقيق نجاح محدود جدا في استخدام الخلايا الجذعية لعلاج عضلات القلب بعد الذبحة الصدرية.
تمكن فريق البحث في هارفارد كما أشرت من استخلاص خلايا الإنسولين وتكاثرها خارج الجسم ونحن في انتظار تطبيق ذلك علاجيا وهذا قد يستغرق سنوات.
حقن الخلايا الجذعية المستخدم الآن ليس له أي أثر إيجابي ماعدا الأثر (العفوي) الذي يماثل أثر أية مادة غير علاجية. والأخطر من ذلك أن استخدام الخلايا الجذعية كما يحدث في الأردن وكرواتيا وكوريا والهند علاوة على أنه غير أخلاقي فقد يؤدي إلى جلطة في الرئتين وتبلغ نسبة الوفيات فيه قرابة 14% وأعرف من ذهب ليستخدم الخلايا الجذعية لكي يستعيد شبابه ففقد حياته.
الطب الحديث طب مبني على البراهين، والبراهين ليس كما يسوق هؤلاء الدجالون بعرض قصص أناس شفوا من أمراض فحتى لو أحسنا الظن وقلنا بأنهم لم يدفعوا لهم ليدعوا الشفاء فتبقى الحالات الفردية حالات فردية.
أعرف أن ذلك لن يثني البعض عن الذهاب وصرف أموالهم على ما قد يضرهم ولا ينفعهم.
لقد عشنا ذات التجربة مع هاشمي الأعشاب وزنداني علاج كل الأمراض وعلاج الأوزون وحتى كفتة عبدالعاطي. وسنعيشها مستقبلا مع المزيد من المحتالين الذين يحسنون العزف على حاجات المرضى.
أتمنى أن تكون هناك محاكم طبية تتولى التحقيق مع من يستغل حاجات المرضى ويروج علاجات عقيمة على أنها شافية وتتواصل مع الهيئات المشابهة في بلد المعالج المحتال لاتخاذ الإجراءات الجنائية ضده.

8. International Diabetes Federation’s
Diabetes mellitus
Chronic metabolic disorder, characterized by chronic hyperglycemia.
leading to long-term damage, dysfunction and failure of various organs such as the heart kidneys, eyes and foot ulcers.
It affects about 8.3 % of the world’s population
International Diabetes Federation’s

9. Types of Diabetes Type 1 Diabetes mellitus (DM)
Gestational Diabetes

10. Insulin production

12. Islet destruction Vs islet exhaustion

13. Treatment of Diabetes Lifestyle changes Diet Drug Insulin Gene therapy
Cell replacement therapy

14. Diabetes treatment
It is unlikely that a cure for diabetes will come from drug and insulin therapy.
Oral hypoglucemic agents are not adequate for tight control
Insulin therapy is associated with hyper and hypoglycemia
Cellular / functional therapy is probably the future of diabetes treatment!!

16. Functional treatment of diabetes What Has Been Tried:
Whole organ transplantation
Islet transplantation
B cell transplantation
Stem cell therapy
Many hospitals will not do a whole organ transplant unless the patient is also receiving a kidney. The risk of infection due to immunosuppressant therapy can be greater than the health issues associated with diabetes. According to the National Institutes of Health, most patients receiving whole-organ pancreas transplants are free of the symptoms of diabetes and do not require insulin injections.
Diabetes can damage the kidneys. High levels of blood sugar make the kidneys filter too much blood. This extra work is hard on the filters in the kidneys and after a period of years of being stressed, the filters start to leak. As a result, useful protein is lost from the body in the urine. Eventually, the stress of overwork results in the kidneys losing their ability to filter. Waste products build up in the blood. Eventually the person will require a kidney transplant or dialysis.

17. Whole organ pancreas transplants
Advantage
Good blood sugar control
Less or no insulin injections
Problem:
not enough organs to meet the demand
must take powerful immunosuppressants
Many hospitals will not do a whole organ transplant unless the patient is also receiving a kidney. The risk of infection due to immunosuppressant therapy can be greater than the health issues associated with diabetes. According to the National Institutes of Health, most patients receiving whole-organ pancreas transplants are free of the symptoms of diabetes and do not require insulin injections.
Diabetes can damage the kidneys. High levels of blood sugar make the kidneys filter too much blood. This extra work is hard on the filters in the kidneys and after a period of years of being stressed, the filters start to leak. As a result, useful protein is lost from the body in the urine. Eventually, the stress of overwork results in the kidneys losing their ability to filter. Waste products build up in the blood. Eventually the person will require a kidney transplant or dialysis.

18. Cell replacement therapy
3 basic approaches:
1. Islet Cell Transplantation
replacement of insulin-producing cells with mature, functioning cells from cadaver organ donors
2. Stem Cell Therapy to Regenerate Islet Function
replacement of insulin-producing cells with stem cell-derived insulin- producing cells
a. stem cells isolated and differentiated in vitro, then transplanted
b. stem cells isolated and transplanted, differentiate in vitro
C. stem Cell Therapy to Prevent Diabetes Onset
3. modification of host immune system by stem cell-derived immune modulatory cells

19. Sources of Beta Cells Transplantable b-cells
Embryonic Stem Cells, Allo
Transplantable
b-cells
Adult b-cells, Allo
Adult b-cells, Auto
Pig Islets, Xeno
Pancreatic Stem Cells,
or Pancreatic Precursors,
Adult, Auto
Liver Cells, Transdifferentiation

20. Islet transplantation

21. Pancreatic harvesting

23. Final islet preparation

24. Islet transplantation

25. Transplantation of Pancreatic Islet Cells
Advantage
Good blood sugar control
Less or no insulin injections
Problem:
less than 10% of these transplants have
been successful
not enough organs to meet the demand
must take powerful immunosuppressants
Many hospitals will not do a whole organ transplant unless the patient is also receiving a kidney. The risk of infection due to immunosuppressant therapy can be greater than the health issues associated with diabetes. According to the National Institutes of Health, most patients receiving whole-organ pancreas transplants are free of the symptoms of diabetes and do not require insulin injections.
Diabetes can damage the kidneys. High levels of blood sugar make the kidneys filter too much blood. This extra work is hard on the filters in the kidneys and after a period of years of being stressed, the filters start to leak. As a result, useful protein is lost from the body in the urine. Eventually, the stress of overwork results in the kidneys losing their ability to filter. Waste products build up in the blood. Eventually the person will require a kidney transplant or dialysis.

26. “The road to edmonton”
7 consecutive patients achieved euglycemia during a mean follow-up of 11 months, with normal HgbA1c and GTT
6/7 patients required >1 donor (>1 transplant) a median of 29 days from the first procedure
Mean islet equivalents =11,400/kg required to achieve euglycemia
Cadaveric pancreata from older donors >45 yo (70% would have been discarded)
Shapiro AMJ et al, NEJM 2000; 343:230

27.  Cells injection into the patient’s pancreas
Advantage
Good blood sugar control
Less or no insulin injections
Problem:
There is much work to be done before this technique will be ready
Many hospitals will not do a whole organ transplant unless the patient is also receiving a kidney. The risk of infection due to immunosuppressant therapy can be greater than the health issues associated with diabetes. According to the National Institutes of Health, most patients receiving whole-organ pancreas transplants are free of the symptoms of diabetes and do not require insulin injections.
Diabetes can damage the kidneys. High levels of blood sugar make the kidneys filter too much blood. This extra work is hard on the filters in the kidneys and after a period of years of being stressed, the filters start to leak. As a result, useful protein is lost from the body in the urine. Eventually, the stress of overwork results in the kidneys losing their ability to filter. Waste products build up in the blood. Eventually the person will require a kidney transplant or dialysis.

28. Stem cells ?
Provide type l diabetics with transplants of cells derived from embryonic stem cells.
* Embryonic
*adult
*Induced
This treatment would be feasible if the patient no longer has any functional beta cells.
Beta cell transplants may require that the recipient take immunosuppressant drugs. Transplants of entire islets require immunosuppressant drugs. Another issue is an adequate supply of islets from human cadavers.
Source: International Society for Stem Cell Research

29. What We Need to Know What properties make embryonic stem cells unique?
Where do these cells come from?
How are they involved in the formation of the pancreas, cells, and other tissues?
Totipotent cells, from the very early cleavage stages, can form the placental and other extra embryonic tissues. Totipotent cells are therefore able to differentiate and form an entire organism. Adult stem cells are much more restricted in what they can differentiate into. They are able to form cells of the type of tissue they are derived from.
Embryonic stem cells are classified as pluripotent. They are able to differentiate into almost any cell in the body. They can form any of the tissues of the ectoderm, mesoderm, and endoderm. They cannot form extra embryonic tissues and therefore cannot differentiate to form an individual organism.

30. What makes Stem cells unique?
can regenerate an infinite number of times
can be grown in culture indefinitely
are classified as pluripotent
are able to differentiate into specialized cells.
Human embryonic stem cells are pluripotent.

31. Forming Specialized Cells
Embryonic stem cells can be directed to become specific cell types if the signals involved in the process and their timing is known.
The same growth factors and signals could be used to direct the differentiation of human embryonic stem cells grown in culture.

32. What is Known
Early endoderm cells receive specific signals at critical times. Signals include transcription factors, cytoplasmic factors, and growth factors. Signals also include physical contact with other cells. The specific combination and timing of signals direct which cell types these cells will differentiate to form. In the illustration, first pancreatic bud cells form. Some of these cells form the endocrine pancreas. By following the normal progression of events, researchers know that signals from adjacent blood vessels are needed for β cells to differentiate from those of the endocrine pancreas. If there is not direct contact between future β cells and blood vessels, β cells will not form.

33. The Task:
Guiding cultured embryonic stem cells to become insulin-producing  cells.

34. Take home messages 2. clinical studies are still at the beginning
1.the # of labs around the world working in this field is increasing
2. clinical studies are still at the beginning
3. at least about 4-5 years are needed before using human embryonic stem cell-based products.
4.Several challenges have to be overcome
- source
- isolation
- immune rejection
5. What works in mice often doesn’t work in humans
6.it is premature for the media to talk about “cures” for Diabetes!!!.

35. The reality:

36. The reality