Stromal cells cultivated from the choroid of human eyes display a mesenchymal stromal cell (MSC) phenotype and inhibit the proliferation of choroidal vascular endothelial cells in vitro.

Mesenchymal stromal cells (MSC), with progenitor cell and immunological properties, have been cultivated from numerous vascularized tissues including bone marrow, adipose tissue and the corneal-limbus of the eye. After observing mesenchymal cells as contaminants in primary cultures of vascular endothelial cells derived from the choroidal tunic of the human eye, we investigated whether the choroid might also provide a source of cultured MSC. Moreover, we examined the effect of the choroidal stromal cells (Ch-SC) on the proliferation of freshly isolated choroidal vascular endothelial cells (ChVEC) in vitro. The phenotype of cultures established from five choroidal tissue donors was examined by flow cytometry and immunocytochemistry. The potential for mesenchymal cell differentiation was examined in parallel with MSC established from human bone marrow. Additional cultures were growth-arrested by treatment with mitomycin-C, before being tested as a potential feeder layer for ChVEC. The five unique cultures established from choroidal stroma displayed a phenotype consistent with the accepted definition for MSC (CD34-, CD45-, HLA-DR-, CD73+, CD90+, and CD105+), including the capacity for mesenchymal differentiation when cultivated under osteogenic, adipogenic and chondrogenic conditions. Growth-arrested Ch-SC inhibited the proliferation of ChVEC derived from five separate donors. Cultures of Ch-SC secreted approximately 40-fold higher concentrations of the anti-angiogenic factor pigment epithelium derived factor (PEDF/serpin F1) compared to the pro-angiogenic factor, vascular endothelial growth factor (VEGF), regardless of normal or growth-arrested state. Our results provide first evidence of a resident MSC cell type within the choroid and encourage investigation of new mechanisms for altering the growth of ChVEC.

Kidney measures with diabetes and hypertension on cardiovascular disease: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Whether the association of chronic kidney disease (CKD) with cardiovascular risk differs based on diabetes mellitus (DM) and hypertension (HTN) status remains unanswered. METHODS: We investigated 11,050 participants from the Atherosclerosis Risk in Communities Study (fourth examination (1996-1998)) with follow-up for cardiovascular outcomes (coronary disease, heart failure and stroke) through 2009. Using the Cox regression models, we quantified cardiovascular risk associated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) in individuals with and without DM and/or HTN and assessed their interactions. RESULTS: Individuals with DM and HTN generally had higher cardiovascular risk relative to those without at all the levels of eGFR and ACR. Cardiovascular risk increased with lower eGFR and higher ACR regardless of DM and HTN status (e.g. adjusted hazards ratio (HR) for eGFR 30-44 vs. 90-104 ml/min/1.73 m(2), 2.32 (95% CI, 1.66-3.26) in non-diabetics vs. 1.83 (1.25-2.67) in diabetics and 2.45 (2.20-5.01) in non-hypertensives vs. 1.51 (1.27-1.81) in hypertensives and corresponding adjusted HR for ACR 30-299 vs. <10 mg/g, 1.70 (1.45-2.00) vs. 1.34 (1.10-1.64) and 1.42 (1.10-1.85) vs. 1.57 (1.36-1.81), respectively). Only the ACR-DM interaction reached significance, with a shallower relative risk gradient among diabetics than among non-diabetics (p = 0.02). Analysis of individual cardiovascular outcomes showed similar results. CONCLUSION: Although individuals with DM and HTN generally had higher cardiovascular risk relative to those without these complications, both low eGFR and high ACR were associated with cardiovascular diseases regardless of the presence or absence of DM and HTN. These findings reinforce the importance of CKD in cardiovascular outcomes.