Session Details

Plenary Session 2 – Complex Cellular Structures: Realising The Regenerative Potential of Cells
Thursday, May 30, 2019 01:45 PM - 03:15 PM
Plenary Hall
Co-Chairs:
Oscar K. Lee MD, PhD, National Yang-Ming University, Taiwan
Janet Macpherson PhD, GE Healthcare Life Sciences, Australia

Speakers:

Advancing the Applications of Human Pluripotent Stem Cell-Derived Kidney Organoids
Melissa Little, PhD, Murdoch Children's Research Institute, Australia

The development of protocols for the differentiation of human pluripotent cells to complex multicellular organoids provides novel opportunities for stem cell medicine. We have developed a protocol for the generation of multicellular human kidney organoids from human pluripotent stem cells (Takasato et al, Nature, 2015; Nature Protocols, 2016). The application of kidney organoids for disease modelling, drug screening or tissue therapy options will require evidence that kidney organoids are an accurate model of the developing human kidney tissue and that the protocols for generation of such tissue are robust, transferable, able to be scaled and can result in a functional tissue. Using CRISPR/Cas9 gene edited iPSC lines, we are comprehensively examining both the lineage relationships of the cell types within kidney organoids and the identity of the component cells and comparing these to what is known in both developing mouse and human fetal tissues. Via single cell transcriptional profiling, we have examined the cellular complexity of kidney organoids, identifying the underlying sources of batch variation and the identity of potential off target cell types. Using changes in culture format, we are developing approaches for the scale up of tissue generation. Transplantation of these human pluripotent stem cell-derived kidney organoids has revealed evidence for vascularisation and maturation, as evidenced by improved ultrastructure.  Altogether, these advances are moving us closer to the application of patient-derived kidney organoids for tissue regeneration.

Tissue-Engineering the Gastrointestinal Tract from Adult and Human Pluripotent Stem Cells
Tracy Grikscheit, MD, Children's Hospital of Los Angeles, USA

The availability of novel stem cell therapies is one of the most exciting, imminent changes in medicine and surgery this decade.  Currently, surgical resection or correction of a congenital malformation often requires either tissue substitution or implantation of a foreign body, and both have serious disadvantages. In the case of small children, there may not be adequate tissue available for substitution. For biomaterials, three problems headline the list of deficits: mechanical or material failure, inadequate size as the child grows, and the lack of true biologic replacement. Organ transplantation has demonstrated the utility of physiologic replacement of form and function, but is still restricted by supply, morbidities of immunosuppression, and outcomes. The promise of stem/progenitor cell therapy is to improve in any or many of these categories, for example by off-the-shelf availability, reduction or removal of immunosuppression, improved longevity, and enhanced or more predictable biology.    Tissue-engineering the gastrointestinal tract and its components is the next frontier for adult and pluripotent stem cell therapies.

Clinical Application of Engineering Cell Sheet for Cardiac Repair
Yoshiki Sawa, MD, PhD, Osaka University, Japan

Although LVAD implantation and Heart transplantation have been well accepted as the ultimate lifesaving means of supporting end-staged heart failure patients, there are some limitations in such therapies. So we developed cell sheet technology experimentally and introduced this to the treatment of severely damaged myocardium as translational research.
In a series of pre-clinical experiments, we proved that myoblast sheets could heal the impaired heart mainly by cytokine paracrine effect in cardiomyopathy model. We applied myoblast sheets to 4 DCM patient receiving LVAD and 2 patients showed the recovery from LVAD. Although we implanted myoblast sheet to 17 heart failure patients with ischemic etiology and majority in patients showed improvement of systolic function with ameliorated exercise tolerance and symptoms. Although in 24 NIDCM patients who were received myoblast sheet functional recovery was limited, good clinical outcome in selected NIDCM patients with preoperatively preserved diastolic function and ability of protein synthesis in myocytes accessed by expression of histone H3 lysine 4 trimethylation. In biopsy sample. Recently myoblast sheet was approved by the government as “Heart Sheet” in the treatment for ischemic cardiomyopathy.
To supply cardiomyocytes to the distressed myocardium we have developed human iPS cell derived cardiomyocyte sheet and obtained Proof of Concept with evidence of synchronous movement with recipient myocardium. And also we have established large culture system and checked safety of GMP grade iPS cell derived cardiomyocyte sheets for clinical trial by the development in new method for removal of immature iPS cells.
Regenerative technology has some potentials in the clinical treatment of heart failure which has little response to the internal medical or conventional surgical treatment and these technologies may open new era in the treatment of severely damaged myocardium.