Abstract
Stem cells, specifically embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), induced pluripotent stem cells (IPSCs), and neural progenitor stem cells (NSCs), are a possible treatment for stroke, Parkinson’s disease (PD), and Huntington’s disease (HD). Current preclinical data suggest stem cell transplantation is a potential treatment for these chronic conditions that lack effective long-term treatment options. Finding treatments with a wider therapeutic window and harnessing a disease-modifying approach will likely improve clinical outcomes. The overarching concept of stem cell therapy entails the use of immature cells, while key in recapitulating brain development and presents the challenge of young grafted cells forming neural circuitry with the mature host brain cells. To this end, exploring strategies designed to nurture graft-host integration will likely enhance the reconstruction of the elusive neural circuitry. Enriched environment (EE) and exercise facilitate stem cell graft-host reconstruction of neural circuitry. It may involve at least a two-pronged mechanism whereby EE and exercise create a conducive microenvironment in the host brain, allowing the newly transplanted cells to survive, proliferate, and differentiate into neural cells; vice versa, EE and exercise may also train the transplanted immature cells to learn the neurochemical, physiological, and anatomical signals in the brain towards better functional graft-host connectivity.
Highlights
Neurological diseases such as stroke, Parkinson’s disease (PD), and Huntington’s disease (HD) remain significant contributors to long-term disability and financial burden for patients worldwide
HD rats exposed to EE had increased striatal BDNF levels, increased graft spinal densities, and larger cell volumes compared to the exercise group
Stem cell therapy relies on cell replacement, and necessitates successful graft-host functional integration
Summary
Neurological diseases such as stroke, Parkinson’s disease (PD), and Huntington’s disease (HD) remain significant contributors to long-term disability and financial burden for patients worldwide. Organoids are in vitro 3D models grown from either pluripotent embryonic stem cells or adult stem cells (Grassi et al, 2019) Such a 3D model reflects the complex tissue organization of the host tissue that a single cell layer culture cannot and can generate from all three germ layers if derived from ESCs or IPSCs. brain tissue organoids are made from neural progenitor cells (NPCs), which can differentiate into neurons and astrocytes (Rossi et al, 2018; Grassi et al, 2019; Corrò et al, 2020). Exercise promotes positive effects on neurogenesis, trophic factor secretion, motor recovery following ischemia, cognitive and motor function, and neuroprotection (Pang et al, 2006; Mang et al, 2013; Tsai et al, 2019) Harnessing these beneficial effects of EE and exercise in combination with stem cell therapy holds significant promise for advancing treatment in stroke, PD, and HD, where therapeutic options remain limited
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