Zurab Kakabadze1, Ann Kakabadze1, David Chakhunashvili1, Lia Karalashvili1, Ekaterine Berishvili1, Yogeshwar Sharma2, Sanjeev Gupta2,3,4,5,6,7. 1. Department of Clinical Anatomy, Tbilisi State Medical University, Tbilisi, Georgia. 2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY. 3. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY. 4. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY. 5. Diabetes Center, Albert Einstein College of Medicine, Bronx, NY. 6. The Irwin S. and Sylvia Chanin Institute for Cancer Research, Albert Einstein College of Medicine, Bronx, NY. 7. Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY.
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 99m Tc-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 2018;67:1956-1969).
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 99m Tc-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 2018;67:1956-1969).
Authors: Z Kakabadze; S Gupta; A Pileggi; R D Molano; C Ricordi; G Shatirishvili; G Loladze; K Mardaleishvili; M Kakabadze; E Berishvili Journal: Am J Transplant Date: 2013-09-06 Impact factor: 8.086
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