Transplants of Human Mesenchymal Stem Cells Improve Functional Recovery After Spinal Cord Injury in the Rat

Abstract

Human mesenchymal stem cells (hMSCs) derived from adult bone marrow represent a potentially useful source of cells for cell replacement therapy after nervous tissue damage. They can be expanded in culture and reintroduced into patients as autografts or allografts with unique immunologic properties. The aim of the present study was to investigate (i) survival, migration, differentiation properties of hMSCs transplanted into non-immunosuppressed rats after spinal cord injury (SCI) and (ii) impact of hMSC transplantation on functional recovery. Seven days after SCI, rats received i.v. injection of hMSCs (2x10(6) in 0.5 mL DMEM) isolated from adult healthy donors. Functional recovery was assessed by Basso-Beattie-Bresnahan (BBB) score weekly for 28 days. Our results showed gradual improvement of locomotor function in transplanted rats with statistically significant differences at 21 and 28 days. Immunocytochemical analysis using human nuclei (NUMA) and BrdU antibodies confirmed survival and migration of hMSCs into the injury site. Transplanted cells were found to infiltrate mainly into the ventrolateral white matter tracts, spreading also to adjacent segments located rostro-caudaly to the injury epicenter. In double-stained preparations, hMSCs were found to differentiate into oligodendrocytes (APC), but not into cells expressing neuronal markers (NeuN). Accumulation of GAP-43 regrowing axons within damaged white matter tracts after transplantation was observed. Our findings indicate that hMSCs may facilitate recovery from spinal cord injury by remyelinating spared white matter tracts and/or by enhancing axonal growth. In addition, low immunogenicity of hMSCs was confirmed by survival of donor cells without immunosuppressive treatment.

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

“…MSCs (1) are easily harvested; (2) are free of ethical issues; (3) are not immunoreactive; (4) can be used for allogenic and xenogeneic transplantation (because of the lack of immune reaction with HLA class II antigen) (Barry 2003;Cizkova et al 2006;Rousseau et al 2007); (5) are not tumorigenic (because they are not immortal, unlike embryonic stem cells); (6) have advantages for clinical applications (because they can be segregated and incubated relatively easily) (Chopp and Li 2002;Preston et al 2003;Prockop 1997;Sakai et al 2005); and (7) have been proven to be a valuable treatment option for full-thickness articular cartilage defects, osteogenesis imperfecta, and myocardial infarction (Wakitani et al 1994;Horwitz et al 1999). Therefore, research on MSCs has recently intensified (Jiang et al 2002).…”

Low-level laser therapy for spinal cord injury in rats: effects of polarization

“…Various strategies have been examined for repair of SCI in animal models, including blockage of the endogenous growth inhibitory factors, 1,2 infusion of neurotrophic factors, 3,4 and transplantation of growth promoting cells. [5][6][7] However, no effective treatment for SCI has yet been established.…”

Mesenchymal stem cells in the treatment of spinal cord injuries: A review

“…Despite promising data, further research is needed to establish whether bone marrow cell treatments can serve as a safe and efficacious autologous source for the treatment of SCI [47] . However, the use of BMSC in SCI does present certain issues-migration beyond the injection site (for intraspinally delivered cells) is limited and rostro-caudal to the injury epicenter, and facilitate recovery from SCI by remyelinating spared white matter tracts and/or by enhancing axonal growth [42] . In our laboratory, we used mesenchymal stem cells from rat bone marrow to evaluate the therapeutic potential after SCI in rats [43] .…”