Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure

Zurab Kakabadze, Ann Kakabadze, David Chakhunashvili, Lia Karalashvili, Ekaterine Berishvili, Yogeshwar Sharma, Sanjeev Gupta

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Tissue engineering with scaffolds to form transplantable organs is of wide interest. Decellularized tissues have been tested for this purpose, although supplies of healthy donor tissues, vascular recellularization for perfusion, and tissue homeostasis in engineered organs pose challenges. We hypothesized that decellularized human placenta will be suitable for tissue engineering. The universal availability and unique structures of placenta for accommodating tissue, including presence of embedded vessels, were major attractions. We found decellularized placental vessels were reendothelialized by adjacent native cells and bridged vessel defects in rats. In addition, implantation of liver fragments containing all cell types successfully hepatized placenta with maintenance of albumin and urea synthesis, as well as hepatobiliary transport of 99mTc-mebrofenin, up to 3 days in vitro. After hepatized placenta containing autologous liver was transplanted into sheep, tissue units were well-perfused and self-assembled. Histological examination indicated transplanted tissue retained hepatic cord structures with characteristic hepatic organelles, such as gap junctions, and hepatic sinusoids lined by endothelial cells, Kupffer cells, and other cell types. Hepatocytes in this neo-organ expressed albumin and contained glycogen. Moreover, transplantation of hepatized placenta containing autologous tissue rescued sheep in extended partial hepatectomy-induced acute liver failure. This rescue concerned amelioration of injury and induction of regeneration in native liver. The grafted hepatized placenta was intact with healthy tissue that neither proliferated nor was otherwise altered. Conclusion: The unique anatomic structure and matrix of human placenta were effective for hepatic tissue engineering. This will advance applications ranging from biological studies, drug development, and toxicology to patient therapies. (Hepatology 2017).

Original languageEnglish (US)
JournalHepatology
DOIs
StateAccepted/In press - Jan 1 2018

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Acute Liver Failure
Placenta
Liver
Tissue Engineering
Albumins
Sheep
Kupffer Cells
Gap Junctions
Hepatectomy
Gastroenterology
Glycogen
Organelles
Toxicology
Blood Vessels
Urea
Regeneration
Hepatocytes
Homeostasis
Endothelial Cells
Perfusion

ASJC Scopus subject areas

  • Hepatology

Cite this

Kakabadze, Z., Kakabadze, A., Chakhunashvili, D., Karalashvili, L., Berishvili, E., Sharma, Y., & Gupta, S. (Accepted/In press). Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. Hepatology. https://doi.org/10.1002/hep.29713

Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. / Kakabadze, Zurab; Kakabadze, Ann; Chakhunashvili, David; Karalashvili, Lia; Berishvili, Ekaterine; Sharma, Yogeshwar; Gupta, Sanjeev.

In: Hepatology, 01.01.2018.

Research output: Contribution to journalArticle

Kakabadze, Z, Kakabadze, A, Chakhunashvili, D, Karalashvili, L, Berishvili, E, Sharma, Y & Gupta, S 2018, 'Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure', Hepatology. https://doi.org/10.1002/hep.29713
Kakabadze Z, Kakabadze A, Chakhunashvili D, Karalashvili L, Berishvili E, Sharma Y et al. Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. Hepatology. 2018 Jan 1. https://doi.org/10.1002/hep.29713
Kakabadze, Zurab ; Kakabadze, Ann ; Chakhunashvili, David ; Karalashvili, Lia ; Berishvili, Ekaterine ; Sharma, Yogeshwar ; Gupta, Sanjeev. / Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. In: Hepatology. 2018.
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