Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma.

Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal stem cells (MSCs) home to sites of tumorigenesis and potently inhibit tumor growth. We further show that human MSCs can inhibit the in vitro activation of the Akt protein kinase within some but not all tumor and primary cell lines. The inhibition of Akt activity requires the MSCs to make direct cell-cell contact and can be inhibited by a neutralizing antibody against E-cadherin. We further demonstrate that in vivo, Akt activation within KS cells is potently down-regulated in areas adjacent to MSC infiltration. Finally, the in vivo tumor-suppressive effects of MSCs correlates with their ability to inhibit target cell Akt activity, and KS tumors engineered to express a constitutively activated Akt construct are no longer sensitive to i.v. MSC administration. These results suggest that in contrast to other stem cells or normal stromal cells, MSCs possess intrinsic antineoplastic properties and that this stem cell population might be of particular utility for treating those human malignancies characterized by dysregulated Akt.

Vitreous hemorrhage in patients with high-risk retinopathy of prematurity.

PURPOSE: To investigate outcomes in premature infants with high-risk retinopathy of prematurity and secondary vitreous hemorrhage. DESIGN: Retrospective chart review. METHODS: Patients were selected from a database of infants undergoing retinopathy of prematurity screening from September 1997 to November 1999. Infants with high-risk retinopathy of prematurity (zone I or posterior zone II threshold disease) with and without vitreous hemorrhage were compared. MAIN OUTCOME MEASURES: Final stage of retinopathy of prematurity and short-term structural outcome were assessed. Visual acuity and refraction were measured when possible. RESULTS: Twenty-two eyes of 11 patients (group 1) had high-risk (posterior zone II or zone I threshold) retinopathy of prematurity without vitreous hemorrhage. Group 1 patients had a 91% favorable short-term structural outcome. Eight eyes of five infants developed vitreous hemorrhage with high-risk retinopathy of prematurity (group 2). Group 2 patients had only a 12.5% favorable short-term structural outcome. Seven of eight (87.5%) progressed to stage IVa or IVb retinopathy of prematurity. Six eyes underwent vitreoretinal surgery after a median duration of hemorrhage of 36 +/- 29 days (4-70 days). Three eyes developed stage V detachments and three progressed to phthisical degeneration. Final visual acuity was no light perception in three eyes. CONCLUSION: Vitreous hemorrhage, in association with advanced retinopathy of prematurity, is a poor prognostic sign.