Bone Marrow Mesenchymal Stem Cells and Electroacupuncture Downregulate the Inhibitor Molecules and Promote the Axonal Regeneration in the Transected Spinal Cord of Rats

Abstract

Our previous study has reported that electroacupuncture (EA) promotes survival, differentiation of bone marrow mesenchymal stem cells (MSCs), and functional improvement in spinal cord-transected rats. In this study, we further investigated the structural bases of this functional improvement and the potential mechanisms of axonal regeneration in injured spinal cord after MSCs and EA treatment. Five experimental groups, 1) sham control (Sham-control); 2) operated control (Op-control); 3) electroacupuncture treatment (EA); 4) MSCs transplantation (MSCs), and 5) MSCs transplantation combined with electroacupuncture (MSCs + EA), were designed for this study. Western blots and immunohistochemical staining were used to assess the fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs) proteins expression. Basso, Beattie, Bresnahan (BBB) locomotion test, cortical motor evoked potentials (MEPs), and anterograde and retrograde tracing were utilized to assess cortical-spinal neuronal projection regeneration and functional recovery. In the MSCs + EA group, increased labeling descending corticospinal tract (CST) projections into the lesion site showed significantly improved BBB scales and enhanced motor evoked potentials after 10 weeks of MSCs transplant and EA treatment. The structural and functional recovery after MSCs + EA treatment may be due to downregulated GFAP and CSPGs protein expression, which prevented axonal degeneration as well as improved axonal regeneration.

Schwann cells induce Proliferation and Migration of Oligodendrocyte Precursor Cells Through Secretion of PDGF-AA and FGF-2

“…Recently, cell transplantation has been an attractive strategy to provide neurotrophic factors and permissive substrates for axonal extension, and remyelin regenerated or damaged axons after SCI (Xu and Onifer 2009). Different cell types, including neural stem cells (NSCs) (Rao and MayerProschel 2000), oligodendrocyte progenitor cells (OPCs) (Givogri, et al 2006), Schwann cells (SCs) (Oudega and Xu 2006;Xu et al 1997), olfactory ensheathing glial cells (OEGs) (Ma et al 2010), and marrow stroma cells (MSCs) (Ding, et al 2011) have been used as donor cells for transplantation after SCI.…”

Long-term survival, axonal growth-promotion, and myelination of Schwann cells grafted into contused spinal cord in adult rats

“…Since cavity or gap formation is evident following SCI in rats and humans (Oudega and Xu, 2006; Xu and Onifer, 2009), cell transplantation into the lesion site is essential to provide permissive substrates for axonal extension through and beyond it. Different cell types, including neural stem cells (NSCs) (Fujimoto et al, 2012; Sandner et al, 2012), fate-restricted neural and glial precursors (NRPs and GRPs) (Cao et al, 2002; Hill et al, 2004; Mitsui et al, 2005), Schwann cells (SCs) (Deng et al, 2011; Xu et al, 1997; Xu et al, 1995b), olfactory ensheathing glial cells (OEGs) (Feron et al, 2005; Ma et al, 2010), and marrow stroma cells (MSCs) (Ding et al, 2011; Phinney and Isakova, 2005) have been used as donor cells for transplantation after SCI with variable degrees of success. Importantly, genetic modification of transplanted cells could be utilized for gene therapy to enhance morphological and functional restoration (Deng et al, 2011; Girard et al, 2005).…”

Combination of Electroacupuncture and Grafted Mesenchymal Stem Cells Overexpressing TrkC Improves Remyelination and Function in Demyelinated Spinal Cord of Rats

“…Electroacupuncture (EA) which originated in ancient China thousands of years ago is widely used as an adjuvant therapy for many diseases2021222324, especially neurological diseases, including CNS damage and demyelinating diseases. EA has long been used to treat MS in traditional Chinese medicine, but the therapeutic mechanism is still unclear.…”

“…In this connection, EA on Governor Vessel (GV-EA) acupoints is commonly used to treat spinal cord injury because impairment of Governor Vessel is correlated with the damage of spinal cord in Chinese traditional medicine. Indeed, GV-EA has been shown to alleviate the secondary damage after spinal cord injury in animal models212225. Our previous studies have reported that GV-EA could promote the secretion of neurotrophin-3 (NT-3) in injured spinal cord222627.…”