Migration and differentiation of nuclear fluorescence‐labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice

Abstract

There is increasing evidence that bone marrow stromal cells (BMSC) have the potential to migrate into the injured neural tissue and to differentiate into the CNS cells, indicating the possibility of autograft transplantation therapy. The present study was aimed to clarify whether the mouse BMSC can migrate into the lesion and differentiate into the CNS cells when transplanted into the mice subjected to focal cerebral infarct or spinal cord injury. The BMSC were harvested from mice and characterized by flow cytometry. Then, the BMSC were labeled by bis-benzimide, a nuclear fluorescence dye, over 24 h, and were stereotactically transplanted into the brain or spinal cord of the mice. The cultured BMSC expressed low levels of CD45 and high levels of CD90 and Sca-1 on flow cytometry. A large number of grafted cells survived in the normal brain 4 weeks after transplantation, many of which were located close to the transplanted sites. They expressed the neuronal marker including NeuN, MAP2, and doublecortin on fluorescent immunohistochemistry. However, when the BMSC were transplanted into the ipsilateral striatum of the mice subjected to middle cerebral artery occlusion, many of the grafted cells migrated into the corpus callosum and injured cortex, and also expressed the neuronal markers 4 weeks after transplantation. In particular, NeuN was very useful to validate the differentiation of the grafted cells, because the marker was expressed in the nuclei and was overlapped with bis-benzimide. Similar results were obtained in the mice subjected to spinal cord injury. However, many of the transplanted BMSC expressed GFAP, an astrocytic protein, in injured spinal cord. The present results indicate that the mouse BMSC can migrate into the CNS lesion and differentiate into the neurons or astrocytes, and that bis-benzimide is a simple and useful marker to label the donor cells and to evaluate their migration and differentiation in the host neural tissues over a long period.

Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury

“…In vivo fluorescence tracking with GFP suggests that mouse MSCs transplanted into the rat spinal cord migrate towards the injury site within 4 weeks after transplant, and some of these cells express neuronal or astrocytic markers. 71 Functional improvement was also observed in a mouse model, either with 57 or without 72 expression of markers of neurons and astrocytes. Magnetic resonance tracking of implanted adult rat MSCs labeled with iron-oxide nanoparticles into the injured rat brain and spinal cord, either intracerebrally or i.v., demonstrated migration to the lesion site, a very small number of MSCs differentiated into neurons but not astrocytes, and the rats with spinal cord injury demonstrated functional recovery.…”

“…MSCs showed proliferation and migration into the injured cortex, and transplanted cells expressed markers for both neurons and astrocytes. 57,58 Some transplanted MSCs expressed both the neuronal marker MAP2 and the g-aminobutyric acid A (GABA-A) receptor. 59 The potential benefits of FGF2 are supported by studies showing that gene-transfected MSCs expressing this growth factor demonstrated improved functional recovery after stroke compared with MSC transplantation alone.…”

Axonal sprouting into the denervated spinal cord and synaptic and postsynaptic protein expression in the spinal cord after transplantation of bone marrow stromal cell in stroke rats

“…Previous studies show that the BMSCs survive in the ischemic brain, and specifically migrate into the ischemic boundary zone (IBZ) after transplantation (Chen et al, 2001;Irons et al, 2004;Lee et al, 2003;Li et al, 2002). Administration of BMSCs reduces neuronal apoptosis (Chen et al, 2003a), promotes angiogenesis (Chen et al, 2003b), synaptogenesis (Zhang et al, 2006) and neurogenesis (Chen et al, 2004) associated with cerebral ischemia in adult rat brain.…”

A Comparison of Neurosphere Differentiation Potential of Canine Bone Marrow-Derived Mesenchymal Stem Cells and Adipose-Derived Mesenchymal Stem Cells

“…However, a few studies advocated that pre-differentiation of MSCs to the desired lineage prior to transplantation may not be necessary, but these cells could be differentiated into neuronal cells after transplantation [33]. Nevertheless, several recent studies showed that MSCs without pre-differentiation did not possess the ability to differentiate into neuronal cells following transplantation [1,12,13,22,23].…”