Transplantation of bovine adrenocortical cells encapsulated in alginate

Abstract

Current treatment options for adrenal insufficiency are limited to corticosteroid replacement therapies. However, hormone therapy does not replicate circadian rhythms and has unpleasant side effects especially due to the failure to restore normal function of the hypothalamic-pituitary-adrenal (HPA) axis. Adrenal cell transplantation and the restoration of HPA axis function would be a feasible and useful therapeutic strategy for patients with adrenal insufficiency. We created a bioartificial adrenal with 3D cell culture conditions by encapsulation of bovine adrenocortical cells (BACs) in alginate (enBACs). We found that, compared with BACs in monolayer culture, encapsulation in alginate significantly increased the life span of BACs. Encapsulation also improved significantly both the capacity of adrenal cells for stable, long-term basal hormone release as well as the response to pituitary adrenocorticotropic hormone (ACTH) and hypothalamic luteinizing hormone-releasing hormone (LHRH) agonist, [D-Trp6]LHRH. The enBACs were transplanted into adrenalectomized, immunodeficient, and immunocompetent rats. Animals received enBACs intraperitoneally, under the kidney capsule (free cells or cells encapsulated in alginate slabs) or s.c. enclosed in oxygenating and immunoisolating βAir devices. Graft function was confirmed by the presence of cortisol in the plasma of rats. Both types of grafted encapsulated cells, explanted after 21-25 d, preserved their morphology and functional response to ACTH stimulation. In conclusion, transplantation of a bioartificial adrenal with xenogeneic cells may be a treatment option for patients with adrenocortical insufficiency and other stress-related disorders. Furthermore, this model provides a microenvironment that ensures 3D cell-cell interactions as a unique tool to investigate new insights into cell biology, differentiation, tissue organization, and homeostasis.adrenal | alginate encapsulation | cell transplantation | LHRH A drenal insufficiency is the failure of adrenocortical cells to produce adequate amounts of glucocorticoids and/or mineralocorticoids. These steroid hormones play a central role in the body's homeostasis of energy, salt, and fluid; thus, adrenal insufficiency is a potentially life-threatening condition. The most relevant causes of adrenal insufficiency are autoimmune disorders (up to 80%); infectious diseases; hereditary factors; traumatic, metabolic, or neoplastic conditions; or surgical bilateral adrenalectomy, sometimes due to a compulsory therapeutic strategy in the treatment of adrenal tumors or congenital adrenal hyperplasia

Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells

“…Alginate is a natural polysaccharide derived from seaweed that polymerizes rapidly in the presence of cations to form a biocompatible hydrogel [18] and, as such, has gained considerable interest as a biomaterial for cell therapy applications [18][19][20][21]. Alginate encapsulation has previously been investigated for its protective effect on the hypothermic storage of rat hepatocytes, recombinant baby hamster kidney cells, human bone marrow-derived MSCs, mouse embryonic stem cells (ESCs), and human limbal epithelial stem cells [22][23][24][25].…”

Encapsulation of Human Natural and Induced Regulatory T‐Cells in IL‐2 and CCL1 Supplemented Alginate‐GelMA Hydrogel for 3D Bioprinting

“…While this study focused on the encapsulation and 3D bioprinting of Tregs for applications in islet transplantation, the findings could be applied to other types of cell therapies such as adrenocortical, thyroid, and parathyroid cell transplantation. [ 67–69 ]…”

Current Perspective and Advancements of Alginate-Based Transplantation Technologies

“…Other disease models have also used alginate microencapsulation for therapeutic use of xenogeneic stem cell-delivery. Researchers have reported functional alginate encapsulated adrenal SCs for use in adrenal hormone insufficiency diseases [63,64]. Successful alginate encapsulation of neural embryonic stem cells was also reported for targeted cell-delivery serving possible treatment for neural tissue repair in several neurological disorders [65].…”