Delivery Of Bone Marrow Stem Cells Research Articles

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

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) 24h 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. Retinal ischemia was induced in adult Wistar rats by increasing intraocular pressure (IOP) to 130-135mmHg for 55min. BMSCs harvested from rat femur were injected into the vitreous 24h post-ischemia. Functional recovery was assessed 7days 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. 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. 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.

The combined use of transmyocardial laser revascularisation and intramyocardial injection of bone-marrow derived stem cells in patients with end-stage coronary artery disease: one year follow-up

There are a growing number of patients with end-stage coronary artery disease (CAD) and refractory angina. Angiogenesis may be induced by intramyocardial injection of autologous bone marrow stem cells, intensified by inflammation around channels performed by laser. To assess the effect of a combined treatment consisting of transmyocardial laser revascularisation (TLMR) and intramyocardial injection of bone-marrow derived stem cells (bone marrow laser revascularisation, BMLR) in patients with refractory angina one year after the procedure. Five male patients (age 49-78 years) with end-stage diffuse CAD, severe angina (CCS III/IV) despite intensive medical therapy and disqualified from prior coronary artery bypass grafting (CABG) or percutaneous coronary intervention were included. After heart exposure, at sites where CABG was impossible, TMLR was performed with the Holmium: YAG laser combined with injection of 1 mL of bone marrow concentrate into the border zone of a laser channel using a Phoenix handpiece. No deaths in the follow-up period were observed. All patients were in I CCS Class. One year after the procedure,left ventricular (LV) segments treated by BMLR tended to demonstrate stronger myocardial thickening compared to baseline(53.0 ± 7.5% vs. 45.0 ± 9.5%; p = 0.06). Using late gadolinium-enhanced imaging, new myocardial infarction was found after one year only in one LV segment treated by BMLR. The BMLR treated regions in the remaining subjects, as well as regions subtended by left internal thoracic artery in two subjects, did not show new myocardial infarction areas. In contrast,all subjects who underwent only BMLR procedure revealed new and/or more extensive myocardial infarct in regions not treated by BMLR. Intramyocardial delivery of bone marrow stem-cells together with laser therapy is a safe procedure, with improvement in quality of life during follow-up. One year after the procedure, myocardial regions where BMLR was performed tended to demonstrate stronger myocardial thickening observed in cardiac magnetic resonance imaging.