Functional Multipotency of Stem Cells and Recovery Neurobiology of Injured Spinal Cords

Abstract

This invited concise review was written for the special issue of Cell Transplantation to celebrate the 25th anniversary of the American Society for Neural Therapy and Repair (ASNTR). I aimed to present a succinct summary of two interweaved lines of research work carried out by my team members and collaborators over the past decade. Since the middle of the 20th century, biomedical research has been driven overwhelmingly by molecular technology-based focal endeavors. Our investigative undertakings, however, were orchestrated to define and propose novel theoretical frameworks to enhance the field's ability to overcome complex neurological disorders. The effort has engendered two important academic concepts: Functional Multipotency of Stem Cells, and Recovery Neurobiology of Injured Spinal Cords. Establishing these theories was facilitated by academic insight gleaned from stem cell-based multimodal cross-examination studies using tactics of material science, systems neurobiology, glial biology, and neural oncology. It should be emphasized that the collegial environment cultivated by the mission of the ASNTR greatly promoted the efficacy of inter-laboratory collaborations. Notably, our findings have shed new light on fundamentals of stem cell biology and adult mammalian spinal cord neurobiology. Moreover, the novel academic leads have enabled determination of potential therapeutic targets to restore function for spinal cord injury and neurodegenerative diseases.

Keywords: central pattern generation; functional multipotency; induced pluripotent stem cell; locomotion; mesenchymal stromal stem cell; neural oncology; neural stem cell; polymer; recovery neurobiology; serotonin; spinal cord injury.

Fig. 1.

Schematic summary of functional multipotency of stem cells. (A) Besides lineage development, stem cells possess intrinsic capabilities to respond to environmental signaling stimulation to customize the content profile of secretomes and exosomes to stage homeostasis. This capacity can be further tailored by genetically engineering the cells with extra copies of transgenes of desirable molecules. (B) Donor stem cells, prototype or genetically modified, can provide therapeutic benefits through at least three distinct mechanisms that may cast synergistic impacts: (1) homeostatic regulation through functional multipotency to perform target homing to deliver cytokines in interactive manners that are regulated via specific signaling pathways, to establish gap junctions, and to form cell fusion (upper inset); (2) replacement of the dysfunctional or dead host cells; and (3) recruitment of and nourishment for host endogenous stem cells. Therapeutic mechanism No. 1 apparently carries a wide spectrum of regulatory tactics that can be further explored to refine the trophic factor and/or other molecules (e.g., microRNA) secretion at each developmental stage or neural disorder status as NSCs integrate into and prepare, modify, and guide the surrounding CNS environment towards the homeostatic formation and maintenance of a physiologically functioning adult nervous system.