Monday, July 03, 2017

We may never achieve proof in the pig-to-NHP model.

  • AS I am searching for ways to make  large scale HLA identical and haploidentical Islet transplantation feasible,I am more and more convinced that today's ethical dilemmas are  man made ,specifically related to the  Judeo Christian beliefs and the political pressure exerted by the pro life lobby in USA where most research takes place.
  • I am hoping countries like JAPAN and CHINA where such religious restrictions are not  there officially, direct Human trials using embryonal organs matured  in 
    Palaeognathae.ova can be undertaken.
  • Although India has a great potential to pioneer such research  Bureaucratic red tape and  fossilized scientific thinking and  scientific infrastructure which  seems to make either duplication of western research or  research in to bygone er's glories are given importance.and  sometimes  the so called expert committees slavishly endorse the  rules and regulations of the  USA and  european countries  without any deep thought.
  • which leads  some funny rules.
for example  it  is quite legal to have  an abortion  up to 28 weeks under the  MTP act but  human cloning  experimentation has to be limited to 14 days after fertilization.

  • The usefulness and limitations of the diabetic macaque model in evaluating long‐term porcine islet xenograft survival
  • Author / Creator:Graham, Melanie L. Schuurman, Henk‐Jan
  • Summary:Various groups have reported prolonged diabetes reversal and graft function after porcine islet transplantation into diabetic macaques using different experimental designs (macaque source, islet source, type of immunosuppression): subsequently, the International Xenotransplantation Association has published recommendations for entering a clinical trial. Our experiments showed limitations that affected consistent achievement of long‐term survival. We aimed to identify these limitations and underlying causes to emphasize the translational value of this highly relevant type 1 diabetic macaque model. We reviewed data from our institution and literature data on long‐term porcine islet xenograft survival in the diabetic macaque model, especially focusing on aspects of incomplete diabetes reversal relative to macaque normal values. This phenomenon was compared with diabetes reversal in an allo‐islet transplant model in macaques and with chronic insulin treatment of diabetic macaques, all with 180‐day follow‐up. This comparison enabled to identify potential model limitations and underlying causative factors. Especially in the xenograft model, the achievement of long‐term graft survival revealed limitations including chronic, mild hyperglycemia and absence of body weight (BW) gain or even progressive BW loss. Metabolic incompatibilities in glycemic control (i.e., insulin kinetics) between the pig and macaque species underlie chronic, mild hyperglycemia. This phenomenon might not bear relevance for the pig‐to‐human species combination because the glycemic control in pigs and humans is similar and differs from that in nonhuman primates (NHP). Weight loss could be related to changes in the gastrointestinal tract related with local high exposure to orally administered immunosuppressants; these must be given at higher dose levels because of low bioavailability in macaques to achieve systemic exposure at therapeutic levels. This is aggravated by insufficient graft insulin production in proportion to the needs of macaques: this model limitation has no translational value to the pig‐to‐human setting. Nutritional deficits can result in incorrect interpretation of blood glucose levels and C‐peptide levels regarding graft function. Likewise, nutritional status alters physiologic responses, influencing susceptibility to infectious and noninfectious complications. The model‐induced confounding described interferes with accurate interpretation of safety and efficacy studies, which affects the translational value of pig‐to‐NHP islet cell transplant studies to the pig‐to‐human transplant condition. 
  • Subject:Diabetes Glucose Control Immunosuppression Islet Xenotransplantation Nonhuman Primates Pigs Transplant Model Limitations
  • Is Part Of:Xenotransplantation, January 2013, Vol.20(1), pp.5-17 [Peer Reviewed Journal]
  • Identifier:ISSN: 0908-665X ; E-ISSN: 1399-3089 ; DOI: 10.1111/xen.12012 

No comments: