Adrenocortical cell transplantation reverses a murine model of adrenal failure

Abstract

Purpose: Although adrenal insufficiency can be managed with steroid replacement, transplantation of adrenocortical cells may represent a more definitive therapy.

Methods: An adrenal failure model was created by adding stress to mice that underwent staged bilateral adrenalectomy. Murine adrenocortical cells were seeded onto collagen sponges. The grafts were implanted under the renal capsule during the first adrenalectomy. Some mice had an additional graft placed next to the kidney. A contralateral adrenalectomy and a laparotomy were performed 1 week after the first adrenalectomy. Two weeks later, blood was collected for corticosterone measurement; and implants were retrieved for adrenal-specific messenger RNA analysis and histology. Mice that underwent the same procedures but received a graft without cells served as controls.

Results: Control group mortality was 100%. Mice that had only one cell-seeded implant had 42% survival, whereas mice that had 2 cell-seeded implants had 100% survival. Retrieved implants demonstrated viable cells and expression of adrenocortical genes. The plasma corticosterone concentration in animals that survived was similar to that in normal mice.

Conclusion: Cells transplantation restored the adrenocortical function in these mice. Further optimization of this technique could bring a curative therapy to patients with adrenal insufficiency.

Figure 1

Survival of mice that underwent simultaneous bilateral adrenalectomy and cell implantation (Group 1) versus those that underwent simultaneous bilateral adrenalectomy and implantation of a blank sponge (Group 2), p = 0.024.

Figure 2

Survival of mice that underwent staged bilateral adrenalectomy and cell implantation (Group 5) versus those that underwent staged bilateral adrenalectomy and implantation of a blank sponge (Group 6), p = 0.11. Comparison between mice in Group 6 and mice that underwent staged bilateral adrenalectomy and double cell implantation (Group 7), p = 0.0001.

Figure 3

Histology of the retrieved specimens from Group 7 after 3 weeks of implantation. (A) and (B): Cell-seeded sponge implanted underneath the kidney capsule. (B) is magnification of the inset in (A). (C) and (D): Cell-seeded sponge implanted in the perirenal adipose tissue. (D) is magnification of the inset in (C). S:sponge, P:pancreas, K:kidney.