Reduced liver cell death using an alginate scaffold bandage: A novel approach for liver reconstruction after extended partial hepatectomy

Shteyer, Eyal; Ya’acov, Ami Ben; Zolotaryova, Lidia; Sinai, Avital; Lichtenstein, Yoav; Pappo, Orit; Kryukov, Olga; Elkayam, Tsiona; Cohen, Smadar; Ilan, Yaron

doi:10.1016/j.actbio.2014.02.047

Cited by 29 publications

(18 citation statements)

References 28 publications

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“…Alginates have several unique structural and chemical parameters, appropriate not only for immune isolation but also for the creation of 3D cellular scaffolds that allow artificial organs to function long term in vitro and in vivo (7,8,11). The potential of xenogeneic adrenocortical cells to replace adrenal gland function has already been tested in animal models but requires acquisition of immunodeficiency (12,13).…”

Section: Significancementioning

confidence: 99%

“…Sodium alginate is one of the clinically approved immunoisolating biopolymers; it has already been widely used in a variety of biomedical applications (5)(6)(7)(8)(9)(10). Alginates have several unique structural and chemical parameters, appropriate not only for immune isolation but also for the creation of 3D cellular scaffolds that allow artificial organs to function long term in vitro and in vivo (7,8,11).…”

Section: Significancementioning

confidence: 99%

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Transplantation of bovine adrenocortical cells encapsulated in alginate

Balyura

Gelfgat

Ehrhart‐Bornstein

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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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

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Section: Significancementioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Transplantation of bovine adrenocortical cells encapsulated in alginate

Balyura

Gelfgat

Ehrhart‐Bornstein

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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“…Besides these biological actions, HAM has also a bandage effect (mechanical protection) and an anti‐inflammatory effect by trapping inflammatory cells that undergo apoptosis in the amniotic membrane matrix (Niknejad et al, ). Moreover, liver cells can colonize implanted acellular alginate scaffolds or biodegradable scaffolds that contain growth factors and liver‐derived extracellular matrix, thus enabling the improvement of the remnant liver‐specific functions following extensive hepatectomy (Shteyer et al, ) and inducing liver cell proliferation in the surrounding parenchyma (Hammond et al, ). Indeed, we observed cells expressing Desmin on HAM.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells seeded on a human amniotic membrane improve liver regeneration and mouse survival after extended hepatectomy

Despeyroux

Duret

Gondeau

et al. 2017

J Tissue Eng Regen Med

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Liver failure remains the leading cause of post-operative mortality after hepatectomy. This study investigated the effect of treatment with allogenic mesenchymal stem cells (MSCs) on survival and liver regeneration 48 hr and 7 days after 80% hepatectomy in C57Bl/6 mice. To optimize their biodistribution, MSCs were grown on acellular human amniotic membranes (HAM) and applied as a patch on the remnant liver. This approach was compared with MSC infusion and HAM patch alone. Hepatectomized mice without any treatment were used as control group. Survival rate was calculated and biological and histopathological parameters were analysed to monitor liver function and regeneration. MSCs grown on HAM retained their ability to proliferate, to differentiate into osteoblasts and adipocytes and to respond to pro-inflammatory stimuli. Extended hepatectomy (80%) led to liver failure that resulted in death within 72 hr in 76% of mice. MSC infusion showed an early but transitory positive effect on survival. MSC/HAM patches stimulated regeneration and significantly improved survival rate (54% vs. 24% in the control group at 7 days). They also decreased the severity of hepatectomy-induced steatosis, suggesting a modulation of lipid metabolism in hepatocytes. MSCs were still present on HAM at Days 2 and 7 posthepatectomy. In conclusion, engineered tissue constructs that combine MSCs and HAM improve survival and liver regeneration after 80% hepatectomy in mice. These encouraging results pave the way to potential clinical application.

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“…Mice with implanted alginate scaffolds manifested normal and prolonged enzymatic level and more normal levels of determine protein expression level. In conclusion, implanted alginate scaffolds can support liver remnants after extended partial hepatectomy [52]. Buckley et al developed a porous alginate scaffold with shape-memory properties that recovers its original geometry once hydrated.…”

Section: Alginate (Alg)mentioning

confidence: 99%