Outcome of Xenografted Fetal Porcine Pancreatic Tissue is Superior in Inbred Scid (C.B-17/Icr-scid/scid) Compared to Outbred Nude (CD-1-nu/nu) Mice

Abstract

Nude mice are used as recipients of foreign tissue because of their inability to reject these grafts. Our experience has been that there is variable rejection of fetal porcine insulin-producing tissue transplanted into CD-1 (athymic) outbred nude mice. To examine the suitability of this line of nude mouse as a recipient of the tissue, fetal porcine pancreas was grafted either into these outbred animals or into an inbred mutant strain of mice, the more immunocompromised severe combined immunodeficient (scid) mouse. Eight weeks after transplantation grafts were recovered from recipients and assayed for insulin content. Mean insulin levels were not significantly different between the two groups of mice, but a wider range of values was obtained from grafts recovered from nude (CD-1-nu/nu) mice. Reversal of diabetes in hyperglycemic recipients was achieved in 4 of 8 nude mice and 8 of 8 scid (C.B-17/lcr-scid/scid) mice. The time taken to achieve this was longer in the nudes than the scid mice, 121 +/- 12 vs. 44 +/- 2 days, the grafts increasing in size at a slower rate in the nude mice. Time taken for the weight of the grafts to double in size was 94 +/- 17 vs. 32 +/- 1 days, respectively. Histologically the grafts in the scid mice contained mostly epithelial cell clusters, a majority of which were insulin containing. In the nude mice that achieved normoglycemia, a similar pattern was observed and, as well, there was a localized lymphoid infiltrate. In those nude mice that remained diabetic fibrous tissue predominated together with a lymphoid infiltrate. In summary, fetal porcine pancreatic tissue grows and develops more efficiently when xenografted into scid rather than outbred nude mice.

Accelerated Preclinical Testing Using Transplanted Tumors from Genetically Engineered Mouse Breast Cancer Models

“…Higher natural killer cell activity was reported in athymic nude mice (33). Differences in the growth rates of normal tissues (34) and inconsistencies in the response to therapies of tumors grown in athymic nude and scid mice have been previously reported (35). Differences in gene expression profiles of tumors grown in athymic nude and scid mice confirm the importance of host immune responses (36).…”

Role of Pancreatic Polypeptide as a Market of Transplanted Insulin-Producing Fetal Pig Cells

“…They were glycemic male severe combined immunodeficient (SCID) mice, as has been described previously (23). We have washed twice with HEPES-buffered Earle's medium, which consists of 124 mM NaCl, 5.4 mM KCl, 1.8 mM shown that these grafts will normalize blood glucose levels of diabetic recipients 5-8 weeks after being trans-CaCl 2 , 0.8 mM MgSO 4 , 1 mM NaH 2 PO 4 , 14.3 mM NaHCO 3 , and 2 mM glucose supplemented with 0.2% planted (23). In initial experiments the tissue was placed beneath the left renal capsule only, but in later experi-bovine serum albumin (Sigma) and 10 mM HEPES.…”

“…Glucagon from the α-cells normalizing blood glucose levels when transplanted into and somatostatin from the δ-cells cannot be used bediabetic rodents (9,11,17,23). The time taken to achieve cause the peptide is indistinguishable in the pig and the this goal is 2-4 months during which there is an inrodent.…”

Secretion of Pancreatic Icosapeptide from Porcine Pancreas

“…Uncultured 1-mm 3 fragments of fetal pig pancreas were transplanted beneath the renal capsule of NOD-SCID mice as described previously (6). Uncultured 1-mm 3 fragments of fetal pig pancreas were transplanted beneath the renal capsule of NOD-SCID mice as described previously (6).…”

“…Insulinproducing fetal pig cells are capable of normalizing blood glucose levels when transplanted into diabetic mice (2)(3)(4)(5)(6) and rats (7). Insulinproducing fetal pig cells are capable of normalizing blood glucose levels when transplanted into diabetic mice (2)(3)(4)(5)(6) and rats (7).…”