New Insights into the Neural Differentiation Potential of Canine Adipose Tissue-Derived Mesenchymal Stem Cells

Abstract

Adipose tissue-derived stem cells (ASCs) can be obtained from different adipose tissue sources within the body. It is an abundant cell pool, easily accessible, suitable for cultivation and expansion in vitro and preparation for therapeutic approaches. Amongst these therapeutic approaches are tissue engineering and nervous system disorders such as spinal cord injuries. For such treatment, ASCs have to be reliably differentiated in to the neuronal direction. Therefore, we investigated the neural differentiation potential of ASCs using protocols with neurogenic inductors such as valproic acid and forskolin, while dog brain tissue served as control. Morphological changes could already be noticed 1 h after neuronal induction. Gene expression analysis revealed that the neuronal markers nestin and βIII-tubulin as well as MAP2 were expressed after induction of neuronal differentiation. Additionally, the expression of the neurotrophic factors NGF, BDNF and GDNF was determined. Some of the neuronal markers and neurotrophic factors were already expressed in undifferentiated cells. Our findings point out that ASCs can reliably be differentiated into the neuronal lineage; therefore, these cells are a suitable cell source for cell transplantation in disorders of the central nervous system. Follow-up studies would show the clinical benefit of these cells after transplantation.

The Use of Allogenic Stromal Vascular Fraction (SVF) Cells in Degenerative Joint Disease of the Spine in Dogs

“…i.e. 2×10 6 /1 kg of body mass, based on reports published by other authors and our own clinical observations (10,15,20,21,22).…”

“…MSCs are also widely used in aesthetic medicine, orthopaedics, and the treatment of growth disorders, tendinitis, or joint regeneration. In reconstructive medicine, they are commonly used in the treatment of soft tissue defects (15,27).…”

“…SVFs are widely used in regenerative medicine due to their ability to differentiate into the cells of damaged tissues and organs. An important role in this process is played by their ability to produce hormones, growth factors stimulating cell growth, interleukins (1,15,16), and extracellular matrix proteins (16,17). The main growth factors participating in the initiation and multiplication of ADSCs in the course of regeneration include transforming growth factor beta (TGFβ)-, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and -vascular endothelial growth factor (VEGF) responsible for angiogenesis (18).…”

“…The described abilities increase the regenerative potential of ADSCs and their possible clinical applications in the treatment of damaged nerve tissue, myocytes, tendons, and ligaments in cases of e.g. denervation (7,15).…”

Mesenchymal stromal cells as a choice for spinal cord injury treatment

“…Although most studies showed evidence that MSCs most likely act through their secretions (paracrine effect) [46][47][48] and not via their own integration/differentiation within the host tissue, some authors have reported the potential for MSCs transdifferentiation in cells of the nervous system and have shown that, after infusion into the spinal cord, these cells possibly promote regeneration of neurons because they have neuronal markers [49][50][51][52] . In vitro studies have shown that BM-MSC possess an intrinsic capacity to differentiate into neural-like and glial-like cells and express nestin, βIII-tubulin, neurofilaments, neuronspecific enolase, and glial fibrillary acidic protein (GFAP) [53][54][55] .…”