Stem Cell-Like Dog Placenta Cells Afford Neuroprotection against Ischemic Stroke Model via Heat Shock Protein Upregulation

Abstract

In this study, we investigated the dog placenta as a viable source of stem cells for stroke therapy. Immunocytochemical evaluation of phenotypic markers of dog placenta cells (DPCs) cultured in proliferation and differentiation medium revealed that DPCs expressed both stem cell and neural cell markers, respectively. Co-culture with DPCs afforded neuroprotection of rat primary neural cells in a dose-dependent manner against oxygen-glucose deprivation. Subsequent in vivo experiments showed that transplantation of DPCs, in particular intravenous and intracerebral cell delivery, produced significant behavioral recovery and reduced histological deficits in ischemic stroke animals compared to those that received intra-arterial delivery of DPCs or control stroke animals. Furthermore, both in vitro and in vivo studies implicated elevated expression of heat shock protein 27 (Hsp27) as a potential mechanism of action underlying the observed therapeutic benefits of DPCs in stroke. This study supports the use of stem cells for stroke therapy and implicates a key role of Hsp27 signaling pathway in neuroprotection.

Intravenously Transplanted Human Bone Marrow Endothelial Progenitor Cells Engraft Within Brain Capillaries, Preserve Mitochondrial Morphology, and Display Pinocytotic Activity Toward Blood-Brain Barrier Repair in Ischemic Stroke Rats

“…On the day of transplantation, β‐gal‐positive hBMEPCs were dissociated into single cells by brief trypsin treatment and suspended in PBS at 4 × 10 6 cells per milliliter and kept on ice until transplantation. The cell suspension was injected slowly for 5 minutes into the jugular vein of four randomly selected rats at 48 hours after tMCAO as we previously described .…”

Amnion-derived stem cell transplantation: A novel treatment for neurological disorders

“…[ 62 ] Another study of in vivo and in vitro stroke models found that dog placenta cells (DPC) had neuroprotective properties by way of Hsp27. [ 49 ] In this study, DPCs were shown to increase the expression of Hsp27 near the area surrounding the ischemic lesion. [ 45 ] Since Hsp27 has been shown to have neuroprotective effects, its increased expression is indicative of the mechanism through which DPCs confer neuroprotection.…”

“…[ 48 ] Among the various immunomodulating effects of ASCS are the inhibition of metalloproteinases, reduction of antigen-presenting cells, upregulation of heat shock protein 27 (hsp27), suppression of T cell multiplication, and modification of M1 microglia, which favor inflammation, into the anti-inflammatory M2 type. [ 49 50 51 ] This reversal from an environment favorable for inflammation into an anti-inflammatory one promotes the regeneration of damaged brain cells. [ 24 ]…”

A Showcase of Bench-to-Bedside Regenerative Medicine at the 2010 ASNTR

“…Using dog placenta as a source of embryonic-like stem cells, Yu et al [ 60 ] demonstrated increased cell survival of primary rat neurons/astrocytes that were cocultured with these cells after OGD treatment. The authors demonstrated that the beneficial effect may result from an upregulation of heat shock protein 27.…”