Defining recovery neurobiology of injured spinal cord by stem cell-based multimodal approaches

• Autorzy: Teng Y.D.
• Języki publikacji: EN

Abstrakty

EN

Emerging evidence increasingly suggests that stem cells may help repair the central nervous system through multiple mechanistic strategies that are often concurrent (i.e., Functional Multipotency of Stem Cells). They may serve not only as tissue engineering media tors of cellular reconstitution, but also as vectors for the delivery of molecules and genes. We have now developed a platform technology to determine therapeutic mechanisms of human mesenchymal stromal stem cells (hMSCs) in a dorsal root ganglion coculture system and an intraspinal cord implantation model. The unique poly(lactic-co-glycolic) acid scaffolding augments hMSC stemness, engraftment, and function without neural transdifferentiation or mesenchymal lineage development, resulting in robust motosensory improvement, pain and tissue damage mitigation, and myelin preservation in adult rat spinal cord after injury. The scaffolded hMSC-derived neurotrophism, neurogenesis, angiogenesis, antiautoimmunity, and antiinflammation support the propriospinal network, neuromuscular junctions, and serotonergic reticulospinal reinnervation to activate the central pattern generator for restoring hindlimb locomotion. Our findings illuminate “Recovery Neurobiology” — i.e., the injured spinal cord may deploy polysynaptic neural circuits different from normal adulthood pathways for postinjury improvement. I will discuss that how tailored polymer implants containing hMSCs or human neural progenitor cells (hNPCs) may hold significant promise for providing a broad range of insight regarding essential neurological mechanisms required for repairing the adult mammalian spinal cord after injury. Our findings may provide a stem cell-based multimodal approach to investigating and formulating therapeutic strategies to achieve clinically meaningful improvement for SCI and neurodegenerative diseases. FINANCIAL SUPPORT: VA (1-I01-RX000308-01), DoD, CASIS-NASA (GA-2015-222), and a Cele H. and William B. Rubin Family Fund, Inc. Grant for the Gordon Program.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.40

Twórcy

autor

Teng Y.D.

• Department of Physcial Medicine and Rehabilitation, Harvard Medical School/Spaulding Rehabilitation Hospital Network, Cambridge, USA
• Department of Neurosurgery, Harvard Medical School/Brigham and Women’s Hospital, Cambridge, USA
• Spinal Cord Injury Research Program, VA Boston Healthcare System, Boston, UK