Events Calendar

Seminars in Biomedical Engineering

Speaker: Yuguo Lei, Ph.D., Postdoctoral CIRM Scholar, Postdoctoral Fellow, the David Schaffer Laboratory Department of Chemical Engineering, Bioengineering, and Helen Wills Neuroscience Institute, University of California, Berkeley

Talk Title: Building Scalable 3D Culture Systems for the Cost-effective Production of Clinical Grade Cells from Human Pluripotent Stem Cells

Abstract: Building Scalable 3D Culture Systems for the Cost-effective Production of Clinical Grade Cells from Human Pluripotent Stem Cells

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have the capacities for indefinite in vitro expansion and differentiation into presumably all cell types in the human body. They therefore represent highly promising cell sources for numerous biomedical applications, such as cell therapy, tissue engineering, drug discovery and toxicity testing. These applications require large numbers of cells of high quality and purity. For instance, ~105 surviving dopaminergic (DA) neurons, ~109 cardiomyocytes, or ~109 β cells are required to treat a patient with Parkinson�s disease (PD), myocardial infarction (MI), or type I diabetes respectively. Analogously, ~1010 hepatocytes are needed for an artificial human liver, and ~1010 cells may be required to screen a million compound library. Considering the large patient populations with degenerative diseases, as well as the millions of chemical/peptide/nucleotide compounds that can be screened against many cell types, massive numbers of hPSCs are thus needed. It is becoming clear that the current 2D-based cell culture systems are incapable of producing sufficient cells with high quality. An attractive approach for scaling up cell production is to move the cell culture from 2D to 3D, and accordingly several 3D suspension systems have been probed for hPSCs production, specifically cell aggregates, cells on microcarriers, and cells in alginate microencapsulates. While these approaches have some attractive aspects, they also highlight significant challenges for 3D hPSC culture including: i) the use of components from human or animal tissue (such as Matrigel, serum, BSA), which limits reproducibility and scalability as well as poses risks for pathogen and immunogen transfer that are problematic for GMP cell production; ii) substantial cell agglomeration that can lead to differentiation and/or death; iii) shear force in agitated cultures that can compromise cell viability; iv) modest cell expansion rates and low cell yields per volume and v) unclear potential for long term serial expansion.

In this presentation, I will introduce a 3D culture system that utilizes a thermoreversible hydrogel as matrix for versatile and multi-scale hPSC culture. With this simple, defined, scalable, GMP compliant system and protocol that are free of animal derived products, we achieved long-term, high rates of expansion (~20-fold per passage over 5 days, 1072-fold over 280 days, and ~2.0x107 cells/ml gel yield), and high level maintenance of pluripotency (~95%) for multiple hESC and hiPSC lines, all of which offer considerable improvements over the current approaches. Based on this system, we then developed a defined bioprocess for the scalable production of DA neurons from hPSCs for treating PD. We made a small molecule cocktail that can efficiently convert hPSCs into DA progenitors in the 3D hydrogel with a yield of ~8x107 DA progenitors/ml hydrogel and ~80-fold expansion by the end of a 15-day derivation. These cells could survive, mature and function in vivo. I will also present data on using these cells to treat PD in a rodent model. This versatile culture system has the potential to resolve a major challenge that is currently limiting the applications of hPSCs.



Biography: Dr. Yuguo Lei received his B.S. in chemistry from Peking University in Beijing, China and his M.S. in polymer science at Hong Kong University of Science and Technology, Hong Kong. He then went to UCLA for a M.S. in pharmacology and Ph.D. in chemical engineering before doing his postdoctoral research at UC Berkeley.

His research interests are to resolve some unsolved human health problems with hPSC-based products. He develops new technologies to address significant challenges that limit the advancement of hPSC-derived cells or products from the benchtop to the bedside. To achieve this goal, he pursues fundamental advances at the intersection of biomaterial design, molecular, cellular and tissue engineering as well as hPSC biology. The resulting technologies are useful for drug discovery, tissue engineering and cell therapies, and Dr. Lei is applying them to treat a number of degenerative diseases, with a focus on the central nervous system.


Host: David D'Argenio

Location: 132

Audiences: Everyone Is Invited

Contact: Mischalgrace Diasanta