We are developing new concepts and technologies to address significant challenges that limit the advancement of stem cells from the benchtop to the bedside. To achieve this goal, we pursue 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 our lab is applying them to treat a number of degenerative diseases, with a focus on the central nervous system.
Challenges: the gap between biology and therapy
hPSCs, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), can be expanded in vitro and differentiated into all cell types. As a result, they have enormous potential for treating various degenerative diseases / injuries, making artificial tissues and being utilized for drug discovery and toxicity tests. However, several technical challenges must be addressed before hPSCs applications can reach their full potential. The first critical limitation is the need to produce a large number of cells. For example, ~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. Likewise, ~1010 hepatocytes or cardiomyocytes would be required for an artificial human liver or heart, respectively; a similar number of cells are required to screen a library of a million compounds at once. Considering the low survival of transplanted cells in vivo, the large patient populations with degenerative diseases (over 1 million people with PD, 1-2.5 million with type I diabetes, and ~8 million with MI in the US alone), and the giant chemical libraries that can be screened against many targets, a massive number of hPSCs and their derivatives are needed. In addition, for clinical applications, the produced cells should comply with Good Manufacturing Practices (GMP). A second challenge, specifically for cell therapies, is the low survival, integration and function of cells in vivo following transplantation. For instance, only ~6% of transplanted DA neurons or ~1% of injected cardiomyocytes survived in rodent models several months after transplantation. The lesion sites, which typically contain a high concentration of inflammatory cells and factors and a low concentration of O2, nutrients, and growth factors due to the absence of vascular structures, are very hostile to the transplanted cells. The disruption of cell signaling, cell-cell, and cell-matrix interactions during cell preparation before transplantation (termed anoikis), and acute cell apoptosis during the injection, also contribute to the low survival rate. During the past decade, significant advances have been made in hPSC biology and we are now entering the era of translating hPSCs into therapies. Resolving these challenges is becoming critical.
Research Area 1: advanced manufacture of stem cells & synthetic tissues
We are developing a universal culture system for the cost-effective, scalable, GMP compliant production of hPSC-derived cells and tissues
Research Area 2: advanced stem cell therapy
We are developing advanced stem cell therapies by combing biomaterials, stem cells and protein factors. These 3 components can work synergic ally to improve the cell therapy efficiency. Biomaterials can not only fill the disease cavity, but also provide a scaffold for the cell growth and controlled protein delivery. Stem cells can replace the lost cells, while the proteins factors can modulate the hostile disease environment, improve the cell survival
Treating PD with DA neurons in rats:
Research Area 3: advanced biomaterials
We are developing novel biomaterials for in vitro stem cell expansion, and for in vivo stem cell delivery