Peripheral Nerve Regeneration-Adipose-Tissue-Derived Stem Cells Differentiated by a Three-Step Protocol Promote Neurite Elongation via NGF Secretion.
Silvan KleinAndreas SiegmundAndreas EigenbergerValerie HartmannFelix LangewostNicolas HammerAlexandra AnkerKonstantin KleinChristian MorsczeckLukas PrantlOliver FelthausPublished in: Cells (2022)
The lack of supportive Schwann cells in segmental nerve lesions seems to be one cornerstone for the problem of insufficient nerve regeneration. Lately, adipose-tissue-derived stem cells (ASCs) differentiated towards SC (Schwann cell)-like cells seem to fulfill some of the needs for ameliorated nerve recovery. In this study, three differentiation protocols were investigated for their ability to differentiate ASCs from rats into specialized SC phenotypes. The differentiated ASCs (dASCs) were compared for their expressions of neurotrophins (NGF, GDNF, BDNF), myelin markers (MBP, P0), as well as glial-marker proteins (S100, GFAP) by RT-PCR, ELISA, and Western blot. Additionally, the influence of the medium conditioned by dASCs on a neuron-like cell line was evaluated. The dASCs were highly diverse in their expression profiles. One protocol yielded relatively high expression rates of neurotrophins, whereas another protocol induced myelin-marker expression. These results were reproducible when the ASCs were differentiated on surfaces potentially used for nerve guidance conduits. The NGF secretion affected the neurite outgrowth significantly. It remains uncertain what features of these SC-like cells contribute the most to adequate functional recovery during the different phases of nerve recovery. Nevertheless, therapeutic applications should consider these diverse phenotypes as a potential approach for stem-cell-based nerve-injury treatment.
Keyphrases
- peripheral nerve
- stem cells
- adipose tissue
- randomized controlled trial
- poor prognosis
- cell therapy
- growth factor
- insulin resistance
- high fat diet
- palliative care
- cell cycle arrest
- mass spectrometry
- escherichia coli
- south africa
- type diabetes
- cystic fibrosis
- neuropathic pain
- staphylococcus aureus
- skeletal muscle
- climate change
- signaling pathway
- combination therapy
- cell death
- spinal cord injury
- single molecule
- endothelial cells
- cell proliferation
- smoking cessation