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Bioengineered functional humanized livers: An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases 被引量:1

Bioengineered functional humanized livers: An emerging supportive modality to bridge the gap of organ transplantation for management of end-stage liver diseases
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摘要 End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs thr-ough intra-omental transplantation of ex vivo genera-ted bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation. End stage liver diseases(ESLD) represent a major, neglected global public health crisis which requires an urgent action towards finding a proper cure. Orthotropic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients limits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolutionized the field of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate app-lications in specific disease conditions. Earlier studieshave demonstrated the applicability of this particularapproach to generate functional organ in rodent systemby connecting them with portal and hepatic circulatorynetworks. However, such strategy requires very highlevel of surgical expertise and also poses the technicaland financial questions towards its future applicability.Hence, alternative sites for generating secondary organsare being tested in several types of disease conditions.Among different sites, omentum has been proved tobe more appropriate site for implanting several kindsof functional tissue constructs without eliciting muchimmunological response. Hence, omentum may be considered as better site for transplanting humanized bioengineered ex vivo generated livers, thereby creatinga secondary organ at intra-omental site. However, theexpertise for generating such bioengineered organs arelimited and only very few centres are involved for investigating the potential use of such implants in clinicalpractice due to gap between the clinical transplantsurgeons and basic scientists working on the conceptevolution. Herein we discuss the recent advances andchallenges to create functional secondary organs through intraomental transplantation of ex vivo generated bioengineered humanized livers and their furtherapplication in the management of ESLD as a supportivebridge for organ transplantation.
作者 Sandeep Kumar Vishwakarma Chandrakala Lakkireddy Avinash Bardia Syed Ameer Basha Paspala Chaturvedula Tripura Md Aejaz Habeeb Aleem Ahmed Khan Sandeep Kumar Vishwakarma;Chandrakala Lakkireddy;Avinash Bardia;Syed Ameer Basha Paspala;Chaturvedula Tripura;Md Aejaz Habeeb;Aleem Ahmed Khan(Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad 500058, Telangana, India;Dr Habeebullah Life Sciences, Attapur, Hyderabad 500058, Telangana, India;CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Hyderabad 500007, Telangana, India)
出处 《World Journal of Hepatology》 CAS 2018年第11期822-836,共15页 世界肝病学杂志(英文版)(电子版)
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