Decellularized human placenta useful for liver tissue engineering

Reuters Health Information: Decellularized human placenta useful for liver tissue engineering

Decellularized human placenta useful for liver tissue engineering

Last Updated: 2017-12-19

By Will Boggs MD

NEW YORK (Reuters Health) - Decellularized human placenta has been shown to support hepatic tissue growth and provide sufficient tissue for rescue in an acute liver failure model.

The capacity of a scaffold to carry transplanted liver tissue containing all cell types and functions will be of enormous value, Dr. Sanjeev Gupta from Albert Einstein College of Medicine, Bronx, New York, and Dr. Zurab Kakabadze from Tbilisi State Medical University, Tbilisi, Georgia, told Reuters Health in a joint email. "This approach using tissue units, as opposed to seeding with one cell type at a time, differed fundamentally from previous efforts for creating an organ," they said.

Human placenta contains vascular networks for exchanging arterial and venous blood, ample space for transplanted cells or tissues, and extracellular matrix components containing beneficial factors associated with a variety of cell types.

Dr. Gupta, Dr. Kakabadze, and colleagues evaluated the feasibility of using decellularized human placenta as a scaffold for liver fragments containing all cell types and tested the viability of the resulting hepatized placenta in a partial hepatectomy sheep model of acute liver failure.

After decellularization, placental vascular structures remained intact and stroma was well preserved, even after storage in saline for days or after lyophilization and cryopreservation for months, according to the December 6 Hepatology online report.

Liver tissue injected into the placenta maintained its structure with sinusoids and was healthy throughout three days of perfusion in vitro. The hepatized placenta showed evidence of hepatic transport and synthetic functions, as well as evidence of graft perfusion.

Hepatized placenta transplanted into sheep within 60 minutes after partial hepatectomy was well perfused without excessive distention or rupture.

Evaluation of grafts from 1 to 45 days after transplantation showed healthy placental and femoral vessel anastomosis, and histology identified confluent hepatic sheets with hepatocytes and sinusoids containing blood and other cells within enclosures of connective-tissue stroma.

There was also evidence of hepatocyte cell-to-cell communication, as well as glycogen storage and albumin production.

After 20 days, placental grafts weighed an average 193 grams, compared with 163 grams at transplantation (roughly 18% to 19% of healthy liver mass).

Five of seven partial hepatectomy sheep that received hepatized placental transplants survived, compared with none of seven similar sheep that did not receive transplants.

"We were pleasantly surprised by the strength of vessels and scaffold after placenta was digested to remove cells," Dr. Gupta and Dr. Kakabadze said. "It appeared that growth factors in placenta attracted endothelial cells, which was important for avoiding thrombosis and blockages of vessels. We were delighted how anticipated tissue self-assembly was borne out with engraftment and function of transplanted liver over several weeks."

"This approach is essentially ready for clinical trial development," they said. "Preparation and banking of placentae ahead of time in conjunction with organization of donor organ supplies should be helpful. Using tissue from mismatched donors will require immunosuppression similar to that for transplantation of allogeneic organs at present."

Dr. Biman B. Mandal from Indian Institute of Technology Guwahati, in India, who has investigated the use of bioactive blend silk matrices for generating liver constructs, told Reuters Health by email, "The successful use of hepatized placenta in acute liver failure leading to functional regeneration was exciting and very appropriate, because this may allow bridging to orthotopic liver transplantation (OLT) or time for regeneration of the native liver."

"More studies should follow up utilizing the methodology adopted here towards regenerating lost and or non-functional organs/tissues," he said. "These experiences may act as a model to study pathophysiological mechanisms or development of therapies as well."

Dr. T.K. Maiti from Indian Institute of Technology Kharagpur, India, recently reported the use of decellularized caprine liver extracellular matrix as a platform for liver tissue engineering. He told Reuters Health by email, "The present manuscript opens new avenues for the application of the human placenta for tissue engineering applications. However, we must not overlook the aspect that the report did not perform an in-depth evaluation of the functional aspects of the cultured hepatocytes on a long-term basis, which is essential for its successful clinical applications."

"Achieving the placenta tissue from the human sources is an issue," he said. "It involves many of ethical aspects. However, it may be overcome by deriving the placental samples from other mammalian organisms."

"Another aspect is a concern of the efficiency of the hepatized construct to perform over 500 different functions performed by the liver in vivo," Dr. Maiti said. "Most of the strategies reported to date fail to perform many of the crucial functions, thereby reducing their chances for successful clinical applications. In addition to this, the time of maintenance of the hepatic functionality is also essential."


Hepatology 2017.

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