Hepatology – VJRegenMed

Advances in organ bioengineering

admin_vjr_user — Tue, 04 Jan 2022 17:52:19 +0000

Paolo De Coppi, MD, PhD, FMedSci, UCL Great Ormond Street Institute of Child Health & NIHR Biomedical Research Centre, London, UK, provides an overview of the current landscape of bioengineering for organ replacement and some of the key considerations during the development of tissue-engineered organs, including the types of cell and polymers used. He notes that for the regeneration of simple tissues, autologous somatic cells may be sufficient, however, for more complex organs, pluripotent stem cells would likely be required, which would require immunosuppression upon implantation in order to avoid tissue rejection. Dr De Coppi also describes ongoing research into the use of biliary organoids for the repair of the damaged liver. This interview took place during the International Society for Cell & Gene Therapy (ISCT) Annual Meeting 2021.

Utilizing tissue-engineered blood vessels in a clinical setting

Simon Ng — Tue, 04 Jan 2022 13:03:14 +0000

Diane Potart, INSERM, Nantes, France, discusses the potential applications for human tissue-engineered blood vessels, especially in the field of hepatology and cardiovascular disease. Tissue-engineered blood vessels can be useful for patients who have end-stage renal diseases undergoing dialysis, as well as patients undergoing coronary bypass surgery. This interview took place at 6th world congress of the Tissue Engineering and Regenerative Medicine International Society (TERMIS 2021).

Immunogenicity of AAV-based gene therapies

Simon Ng — Mon, 08 Nov 2021 18:22:05 +0000

Whilst adeno-associated viral (AAV) vectors show great promise as effective gene transfer platforms, they have been demonstrated to trigger both innate and adaptive immune responses. Paul Gissen, MD, PhD, UCL Great Ormond Street Institute of Child Health, London, UK, describes the challenge of immune-related adverse events caused by AAV vector-based gene therapy and strategies being investigated to address this. Today, most clinical trials involving AAV vector-based gene therapy screen patients to detect the presence of antibodies against viral vectors as part of the patient enrolment process. Dr Gissen also discusses issues around cytotoxicity and the ongoing development of immunomodulatory regimens currently being developed. This interview took place at the Advanced Therapies Congress & Expo 2021.

Tackling remaining obstacles to cell therapy for type I diabetes

admin_vjr_user — Thu, 19 Aug 2021 11:47:28 +0000

Ekaterine Berishvili, MD, PhD, University of Geneva, Geneva, Switzerland, discusses the key challenges associated with the development of cell-based therapies for type I diabetes. There is currently an insufficient number of cell donors to meet the high demand of patients with type I diabetes that require treatment. Dr Berishvili proposes expanding the cell pool through the transdifferentiation and differentiation of pluripotent stem cells to insulin-producing beta cells, however, notes that this would not necessarily allow the generation of functional islets, given their complexity. Key remaining challenges include recapitulating islet anatomy and function, as well as achieving protection from the host immune system to avoid rejection upon transplantation. This interview took place during the International Society for Cell & Gene Therapy (ISCT) Annual Meeting 2021.

Enhancing AAV gene therapy in children with inborn errors of metabolism

admin_vjr_user — Wed, 18 Aug 2021 16:32:47 +0000

Gloria Gonzalez-Aseguinolaza, PhD, Universidad de Navarra, Pamplona, Spain & Vivet Therapeutics, Paris, France, explains that a key challenge associated with treating inborn errors of metabolism in children using non-integrating vector-based gene therapy is liver growth and therefore hepatocyte addition, which results in the dilution of therapeutic effect and need for re-administration. Subsequent doses are, however, typically less effective due to the presence of neutralizing antibodies following the first injection. Approaches being investigated to overcome this challenge include the use of ImmTOR tolerogenic nanoparticles carrying rapamycin which inhibit neutralising antibody formation, as well as strategies to reduce adeno-associated vector (AAV) genome loss during liver growth. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

The future of cell-based therapies for type 1 diabetes

admin_vjr_user — Wed, 11 Aug 2021 07:54:05 +0000

Ekaterine Berishvili, MD, PhD, University of Geneva, Geneva, Switzerland, discusses the current landscape of cell-based therapies for type I diabetes (T1D) and the future directions of the field. Currently, the most widely used cell-based therapy for T1D is islet transplantation, however, Dr Berishvili indicates that the requirement for several cell donors and lifelong immunosuppression calls for alternative cell-based therapies. She describes new avenues under investigation including the transplantation of stem cell-derived β cells to patients with T1D, as well as promise around the generation of the bioartificial endocrine pancreas and its curative potential. This interview took place during the International Society for Cell & Gene Therapy (ISCT) Annual Meeting 2021.

A novel lentiviral therapeutic approach to primary hyperoxaluria type 1

admin_vjr_user — Fri, 14 May 2021 14:11:24 +0000

Jose-Carlos Segovia, PhD, CIEMAT, CIBERER & IIS- FJD, Madrid, Spain, discusses the limitations associated with the use of adeno-associated virus vectors when targeting primary hyperoxaluria type 1 (PH1), a rare genetic disorder of the liver caused by mutations in the AGXT gene. Given the high integrating capacity of lentiviral vectors, they are being investigated in a preclinical mouse model as a novel therapeutic approach for PH1. Preliminary studies have demonstrated that treatment with hepatocyte-specific lentiviral gene therapy resulted in high levels of gene correction, although further work is required to improve transduction efficiency and enhance therapeutic benefit. This interview took place during the American Society for Cell & Gene Therapy 24th Annual Meeting 2021.

CT053, anti-GPC3 CAR-T and targeting solid tumors

admin_vjr_user — Wed, 10 Mar 2021 19:30:20 +0000

Hong Ma, MD, MSc, MBA, CARsgen Therapeutics, Shanghai, China, provides an overview of recent data obtained from a number of Phase I clinical trials evaluating CT053, a fully human B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory (R/R) multiple myeloma. Studies discussed include LUMMICAR-1 (NCT03975907), LUMMICAR-2 (NCT03915184) and an investigator-initiated program in eastern China (NCT03716856, NCT03302403 and NCT03380039). In addition, Dr Ma describes recent and ongoing studies evaluating anti-GPC3 CAR-T cell therapy in patients with hepatocellular carcinoma. He also discusses overcoming the major challenges associated with targeting solid tumors using CAR-T therapies. This interview took place during the CAR-TCR Summit Europe 2021.

Whole-liver bioengineering: the future of transplantation medicine

admin_vjr_user — Wed, 19 Aug 2020 16:20:19 +0000

Pedro Baptista, PharmD, PhD, of Aragon Health Research Institute, Zaragoza, Spain, outlines whole-liver bioengineering as the future of transplantation and challenges associated with its implementation. Specifically discussed is how dis-used organs can be decellularized and recapitulated with patient-derived tissue to generate new organs that are eligible for transplantation. This interview was recorded via an online conference call with The Video Journal of Regenerative Medicine (VJRegenMed).