Cell & Stem Cell Research

Biography

Biography: Xianmin Zeng

Abstract

For cell-based therapy to treat Parkinson’s disease (PD), we have developed a Good Manufacturing Practice (GMP)-compatible process for generating authentic midbrain (A9/A10) dopaminergic neurons using defined media from either human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC). We have identified the optimal time point at which dopaminergic neurons can be frozen, shipped and thawed without compromising their viability and ability to mature in vivo after transplantation. We have also performed IND-enabling preclinical efficacy and safety studies using cells manufactured by this process. Our results show robust long-term survival of transplanted dopaminergic neurons and functional recovery at 6 months post transplantation in the 6-hydroxydopamine (6-OHDA)-lesioned rat PD model. To optimize the transplantation process we have helped develop and test a surgical delivery catheter that can be integrated with an US Food and Drug Administration (FDA)–approved iMRI skull-mounted aiming device and targeting software. We have demonstrated biocompatibility of the cells with the device and successfully delivered with iMRI guidance into swine models. In summary, 1) we have access to a clinical-grade ESC and iPSC line as well as their matched research grade differentiated cells; 2) We have identified a manufacturing site and have access to the DMF; 3) We have performed preclinical studies with cells manufactured by the GMP-compatible process we have developed and 4) We have coordinated with clinicians on developing a delivery procedure and a surgical trial design.