Skin-Derived Precursor Cells Promote Angiogenesis and Stimulate Proliferation of Endogenous Neural Stem Cells after Cerebral Infarction

Abstract

Stroke is one of the most common diseases that caused high mortality and has become burden to the health care systems. Stem cell transplantation has shown therapeutic effect in ameliorating ischemic damage after cerebral artery occlusion mainly due to their neurogenesis, immune regulation, or effects on the plasticity, proliferation, and survival of host cells. Recent studies demonstrated that skin-derived precursor cells (SKPs) could promote central nervous system regeneration in spinal cord injury model or the neonatal peripheral neuron. Here, we investigated the therapeutic potential of SKPs in a rat model of cerebral ischemia. SKPs were isolated, expanded, and transplanted into rat cortex and striatum after transient middle cerebral artery occlusion. Our results revealed that SKPs transplantation could improve the behavioral measures of neurological deficit. Moreover, immunohistology confirmed that SKPs could secrete basic FGF and VEGF in the ischemic region and further markedly increase the proliferation of endogenous nestin+ and βIII-tubulin+ neural stem cells. Furthermore, increased angiogenesis induced by SKPs was observed by vWF and α-SMA staining. These data suggest that SKPs induced endogenous neurogenesis and angiogenesis and protected neuron from hypoxic-ischemic environment. In conclusion, SKPs transplantation may be a promising approach in treatment of stroke.

Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field for stroke research

“…This connection between neurogenesis and angiogenesis has been demonstrated using endothelial progenitor cell (EPC) and smooth muscle progenitor cell co-transplants (Nih et al, 2012), skin-derived precursor cells (Mao et al, 2015), NSCs (Zhang et al, 2011) and bone marrow-derived MSCs (Bao et al, 2011). …”

Multipotentiality of skin‐derived precursors: application to the regeneration of skin and other tissues

“…Moreover, those differentiated cells express specific keratinocyte markers such as filaggrin and involucrin . Later, the differentiation of SKPs into keratinocyte‐like cells was also demonstrated when spheres were cultured on a collagen‐chitosan scaffold, expressing cytokeratin 14, filaggrin and involucrin .…”

“…Consequently, this approach using animal‐origin‐free and biocompatible 3D hydrogels, as an in vitro niche for SKPs, could be beneficial for fundamental research and clinical applications in the near future. As mentioned above, SKPs can also be used to form a model of in vivo skin when they are differentiated into keratinocyte‐like cells and add onto a scaffold made with collagen and chitosan .…”

The role of the miR‐17–92 cluster in neurogenesis and angiogenesis in the central nervous system of adults

“…NSCs reside in the specific region of brain such as SVZ. Upon damages, NSCs will be mobilized and migrate toward the injury site in 14 days (Yamashita et al, ), and yet have a hard time surviving due to low blood‐supply levels and hypoxia in the local microenvironment (Arvidsson et al, ; Mao et al, ). It has been demonstrated that neovessels can potentially stimulate axonal sprouting (Dray et al, ), thus it is essential to protect the vasculature at maximal extent in order to promote angiogenesis for the functional recovery after CNS injury (Dray et al, ; Fassbender et al, ).…”

“…Recent research progress have disclosed that the neurotrophic and neuroprotective roles of VEGF via its directly influence on neuronal progenitor cells, astrocytes, microglia, and Schwann cells, thus VEGF also act as a key player in neurogenesis. It has been shown that transplantation of skin‐derived precursor cells promoted endogenous neurogenesis and angiogenesis by secreting basic FGF and VEGF (Mao et al, ). Therefore, VEGF may act as a key molecule in the interaction between angiogensis and neurogenesis.…”