Rapid and efficient generation of neural progenitors from adult bone marrow stromal cells by hypoxic preconditioning

published_or_final_versio

Directed differentiation of human bone marrow stromal cells to fate-committed Schwann cells

Transplantation of oligodendrocyte precursors represents a potential therapy for myelin disorders but requires a safe and accessible cell source. Here we report the directed differentiation of neural progenitors derived from adult bone marrow stromal cells (BMSCs) into oligodendrocyte precursors for cell therapy purpose. Neural progenitors among BMSCs could be culture expanded in non-adherent sphere-forming conditions and directed to differentiate along the oligodendrocyte lineage. BMSC-derived oligodendrocyte precursors (BM-OPs) differentiated into myelin basic protein (MBP)-positive oligodendrocyte when co-cultured with purified dorsal root ganglion (DRG) neurons. Injection of BM-OPs into the brain of myelin deficient Shiverer mice resulted in the generation of MBP-positive oligodendrocyte and compact myelin. Our results provided pointers to adult BMSCs as a readily accessible source of OPs towards cell therapy for myelin disorders.published_or_final_versio

ErbB receptor modulation controls the fate commitment of bone marrow-derived Schwann cells

The 2010 Joint Scientific Meeting of the Hong Kong Society of Neurosciences and the Biophysical Society of Hong Kong, Hong Kong, 7-8 June 2010

Fate Commitment in Bone Marrow Stromal Cell Derived Schwann Cells is Dependant on Axonal Contact

Oral Presentations: Session 1 - Healthy Aging: No. 1.1

Targeting Notch Signalling to Generate Bone Marrow-derived Schwann Cells for Transplantation in Spinal Cord Injury

Conference Theme: Defying the Aging Spine - Our Mission ContunuesN104 Concurrent Free Paper 2: Basic Science/General OrthopaedicsThere has been significant interest in Schwann cell transplantation for cell therapy in spinal cord injury. Schwann cells secrete neurotrophic factors, phagocytose inhibitory myelin debris, and remyelinate denuded axons. Although readily harvested from the sural nerve, there is donor site morbidity and hence there remains the need to find an alternative source of easily expansible autologous Schwann cells. Our strategy of deriving Schwann cells from bone marrow stromal cells exploited exposure to growth factors to generate Schwann cell–like cells followed by coculture with purified dorsal root ganglia (DRG) neurons to provide juxtacrine cues mediating commitment to the Schwann cell fate. Immunocytochemistry demonstrated expression of Notch ligands DLL1 and Jagged1 on DRG neurons, while the Notch-1 receptor was expressed by bone marrow–derived Schwann cell–like cells. In cocultures with DRG neurons during which Schwann cell–like cells progressed towards fate commitment, translocation of the Notch intracellular domain to the nucleus was indicative of Notch signalling. Subsequently, ErbB2/B3 receptor heterodimers were upregulated on immunocytochemistry and Western blotting, allowing neuregulins to drive Schwann cell–like cells to fate commitment. Conversely, addition of the Notch inhibitor DAPT led to decreased expression of ErbB receptors. In ongoing work, we are using a neuron-free coculture platform to present Notch ligands to drive Schwann cell–like cells to fate commitment. By understanding the mechanism of coculture-induced fate commitment, we hope to generate an unlimited supply of autologous Schwann cells for use in cell therapy

Schwann cells derived from bone marrow stromal cells – in vitro study with dorsal root ganglia and in vitro study with peripheral nerve conduits

Conference Theme: Improving the Health of an Aging Populatio

Functional study of stem-cell-derived Schwann cells using an in-vitro dorsal root ganglia model

Conference Theme: Improving the Health of an Aging Populatio