We are planning to test insulin-secreting cells differentiated from human stem cells for ability to alleviate type-I diabetes and short- and longterm safety in rats. The model we regularely use is Streptozotocin-induced diabetes in rats. Working on NOD mice is not an option (unfortunately) in our facility. I have met some publications H.M. Kang et al. where the differentiated beta-cells (from human) were able to survive and physiologically function in immunocompetent mice (following xenogenic transplantation). My question is: is it possible in rats (instead of mice) or immunosupression is inevitably.?
Hi,
Alla,
I have done transplantation of differentiated hES cells into Streptozotocin induced mice. The mice were Swiss mice and immunocompetent. I put the cells in polyurethane-polyvinyl pyrrolidone macrocapsules. The microcapsules work well, several groups such as Viacyte have used it successfully. But if you do not want to use encapsulation then you have to supress the immune response.
Regards,
Prasad.
Dear Alla, I am sorry, I am not an expert in this field, although the idea is interesting!
Regards, Miklos
Alla,
As in any allo or xeno-transplant, immunosuppression or isolation will be a necessity for survival of the transplanted cells.
In some cases (in various contexts) tolerization protocols have met some success after an initial induction period.
yes
we did in 1997-98, published in Diabetes 49: 157-162 (2000), you may also check
Diabetologia 47: 1442-1451 (2004)
Stem Cells 24(2): 258-265 (2006)
Exp Cell Res 314: 969-974 (2008) and others
in principle insulin producing cells derived from embryonic stem cells do not induce an immune response, and integrate for periods of 10 to even 40 weeks
when embryonic stem cells are from human origin yo better use SCID mice
good luck
check also
Resveratrol ameliorates the maturation process of β-cell-like cells obtained from an optimized differentiation protocol of human embryonic stem cells.
Pezzolla D, López-Beas J, Lachaud CC, Domínguez-Rodríguez A, Smani T, Hmadcha A, Soria B.
PLoS One. 2015 Mar 16;10(3):e0119904. doi: 10.1371/journal.pone.0119904. eCollection 2015
SCID mice are difficult to keep after STZ treatment, have you tried the Akita model?
Unfortunately we never tried SCID or Akita mice. The problem is that is a big trouble to get such animals from abroad due to customs regulations. I will try to do something but not very optimistic about that. I afraid we will have to stick to rats.
Beta -cells from rat stem cells are working in rats, but for safety trials we have to check B-cells from human
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