論文 - 詳細
| RRC ID | 4343 |
|---|---|
| 著者 | Takayama N, Nishikii H, Usui J, Tsukui H, Sawaguchi A, Hiroyama T, Eto K, Nakauchi H. |
| タイトル | Generation of functional platelets from human embryonic stem cells in vitro via ES-sacs, VEGF-promoted structures that concentrate hematopoietic progenitors. |
| ジャーナル | Blood |
| Abstract |
Human embryonic stem cells (hESCs) could potentially represent an alternative source for blood transfusion therapies and a promising tool for studying the ontogeny of hematopoiesis. When we cultured hESCs on either C3H10T1/2 or OP-9 cells to facilitate hematopoiesis, we found that exogenous administration of vascular endothelial growth factor promoted the emergence of sac-like structures, which we named embryonic stem cell-derived sacs (ES-sacs). These ES-sacs consisted of multiple cysts demarcated by cellular monolayers that retained some of the properties of endothelial cells. The spherical cells inside ES-sacs expressed primarily CD34, along with VE-cadherin, CD31, CD41a, and CD45, and were able to form hematopoietic colonies in semisolid culture and to differentiate into mature megakaryocytes by day 24 in the presence of thrombopoietin. Apparently, ES-sacs provide a suitable environment for hematopoietic progenitors. Relatively large numbers of mature megakaryocytes could be induced from the hematopoietic progenitors within ES-sacs, which were then able to release platelets that displayed integrin alpha IIb beta 3 activation and spreading in response to ADP or thrombin. This novel protocol thus provides a means of generating platelets from hESCs, which could serve as the basis for efficient production of platelets for clinical transfusion and studies of thrombopoiesis. |
| 巻・号 | 111(11) |
| ページ | 5298-306 |
| 公開日 | 2008-6-1 |
| DOI | 10.1182/blood-2007-10-117622 |
| PII | S0006-4971(20)47135-6 |
| PMID | 18388179 |
| MeSH | Blood Platelets / cytology* Blood Platelets / metabolism Cell Culture Techniques / methods* Embryonic Stem Cells / cytology* Embryonic Stem Cells / metabolism Flow Cytometry Hematopoietic Stem Cells / cytology* Hematopoietic Stem Cells / metabolism Humans Immunohistochemistry Megakaryocytes / cytology Megakaryocytes / metabolism Microscopy, Confocal Platelet Activation / physiology Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A / metabolism* |
| IF | 17.794 |
| 引用数 | 179 |
| WOS 分野 | HEMATOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 110 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒトES細胞 | KhES-1 KhES-2 KhES-3 |
| ヒト・動物細胞 | 10T1/2(RCB0247) |