Bone-marrow mesenchymal stem-cell administration significantly improves outcome after retinal ischemia in rats

Abstract

Purpose Ischemia-associated retinal degeneration is one of the leading causes of vision loss and to date, there are no effective treatment options. We hypothesized that delayed injection of bone marrow stem cells (BMSCs) 24 h after the onset of ischemia could effectively rescue ischemic retina from its consequences, including apoptosis, inflammation, and increased vascular permeability, thereby preventing retinal cell loss. Methods Retinal ischemia was induced in adult Wistar rats by increasing intraocular pressure (IOP) to 130–135 mm Hg for 55 min. BMSCs harvested from rat femur were injected into the vitreous 24 h post-ischemia. Functional recovery was assessed 7 days later using electroretinography (ERG) measurements of the a-wave, b-wave, P2, scotopic threshold response (STR), and oscillatory potentials (OP). The retinal injury and anti-ischemic effects of BMSCs were quantitated by measuring apoptosis, autophagy, inflammatory markers, and retinal-blood barrier permeability. The distribution and fate of BMSC were qualitatively examined using real-time fundus imaging, and retinal flat mounts. Results Intravitreal delivery of BMSCs significantly improved recovery of the ERG a- and b-waves, OP, negative STR, and P2, and attenuated apoptosis as evidenced by decreased TUNEL and caspase-3 protein levels. BMSCs significantly increased autophagy, decreased inflammatory mediators (TNF-α, IL-1β, IL-6), and diminished retinal vascular permeability. BMSCs persisted in the vitreous and were also found within ischemic retina. Conclusions Taken together, our results indicate that intravitreal injection of BMSCs rescued the retina from ischemic damage in a rat model. The mechanisms include suppression of apoptosis, attenuation of inflammation and vascular permeability, and preservation of autophagy.

Changes in the secretome of tri-dimensional spheroid-cultured human mesenchymal stem cells in vitro by interleukin-1 priming

“…Key features of MSCs include their ability to sense and migrate toward tumours [ 6 ] and inflamed, ischaemic, or injured tissues [ 7 ]. Additionally, MSCs can cross the blood-brain barrier [ 8 ] and secrete a wide variety of cytokines and trophic mediators [ 2 , 9 , 10 ] that induce tissue repair by activating endogenous protective mechanisms [ 11 , 12 ]. These effects are achieved with a low engraftment rate and low rejection response from the host tissue, which confers MSCs a uniquely high level of safety [ 1 – 3 ].…”

Bone marrow mesenchymal stem cells enhance autophagy and help protect cells under hypoxic and retinal detachment conditions

“…Photoreceptor could be protected by inhibiting apoptosis (through blocking cytochrome c release and caspase‐3 activation, or by suppressing the Fas‐signalling pathway), including deletion of anti‐apoptotic Bax, use of small peptide Met12, neurotrophins and compounds like edaravone and tauroursodeoxycholic acid . Intravitreal delivery of BMSCs also attenuated apoptosis by decreasing caspase‐3 in ischaemic rat retina . Apoptosis was repressed by BMSCs in this study, as coculturing with BMSCs ameliorated morphological changes and apoptotic cells while simultaneously significantly decreased the expression of apoptotic‐related proteins.…”

“…BMSCs were also reported to actively participate in autophagy to ameliorate ischaemia/reperfusion‐induced lung injury and liver fibrosis . More important, BMSCs were reported to protect ischaemic retina by increasing autophagy . However, there has been no report on the effects of BMSCs on photoreceptor damage in retinal detachment.…”

“…15,16 More important, BMSCs were reported to protect ischaemic retina by increasing autophagy. 17 However, there has been no report on the effects of BMSCs on photoreceptor damage in retinal detachment. Thus, our study was to investigate whether the BMSCs could protect detached and hypoxic retina and whether autophagy participates in the effects of BMSCs on retina.…”

Mesenchymale Stammzellen: Tumorfördernde oder -hemmende Eigenschaften – Ein aktueller Überblick

“…Die Entwicklung von nicht-malignem und malignem Gewebe ist auf eine suffiziente Gefäßversorgung angewiesen. Die Fähigkeiten von MSC zur Förderung der Angiogenese wurde mehrfach in Ischämie-Modellen aufgezeigt [60][61][62] Über eine stammzell-induzierte Modifikation der Expression dieser Faktoren werden sowohl pro-als auch anti-angiogene Impulse gegeben [66]. De Boeck und Kollegen konnten zeigen, dass eine Progression von Kopf-Hals-Plattenepithelkarzinomen durch MSC vor allem über eine Verbesserung der Angiogenese erfolgt [67].…”