Dr. Qi Lin Cao
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Neurosurgery
Transplantation of neural stem cells (NSCs) is proved a promised therapeutic approach to promote functional recovery after neurological diseases, including spinal cord injury (SCI) and stroke. However, there is no consensus as to which NSC resource is optimal for SCI. Human central nervous system stem cell isolated from fetal cadaver brain tissue and neural progenitor cells derived from human embryonic stem cells (hESCs)-derived have been approved for clinical trials for SCI patients. However, these cells are associated with ethical controversy and graft rejection. Cells derived from hESCs have additional risk of teratoma formation. Human induced pluripotent stem cells (hiPSCs) are recently developed remarkable pluripotent, ESC-like cells reprogrammed from adult somatic cells by over-expression of four developmental/pluripotency transcription factors. Compared with ESCs, hiPSCs offer significant additional advantages in terms of availability of source material without ethical concerns of embryo use, and especially the ability to generate isografts without the need of immunosuppression. We have developed protocol to differentiate and purify NSC, neuronal precursor cells or glial precursor cells from hiPSCs. Our results show that hiPSC-derived NSCs can proliferate over long time in vitro and be induced to differentiate into functional neurons, astrocytes and oligodendrocytes. Importantly, hiPSC-derived NSCs can survive and differentiate into both neurons and glias after transplantation into the contused spinal cord and promote functional recovery. These studies suggest that transplantation of hiPSC-derived NSC is an effective therapy to preserve and restore neurological functions. Currently, we are testing the therapeutic efficacy and long-term safety of NSCs, neuronal or glial precursor cells to identify the optimal cell graft for SCI and stroke. Recently, we are testing whether we can directly reprogram the astroglial cells in the injured spinal cord or stroke brain into neurons. Astroglial scar are the major inhibitor for axonal regeneration. In situ reprogramming active astrocytes into neuronal precursor cells will decrease astrocyte inhibition to promote axonal regeneration. The newly reprogrammed neuronal precursor cells could replace the lost neurons after SCI or stroke. These two mechanisms may work synergistically to promote great functional recovery after SCI or stroke. Our long-term goal is to develop novel stem cell-based therapies to treat human SCI or stroke.