Superiority of 3-D Hematopoietic Stem Cell (HSC) & Stroma Cell Co-Cultures in Supporting the Proliferation of Transplantable HSC
| Autor: | Shai Meretzki, Dov Zipori, Ora Berger, Jacob M. Rowe, Avinoam Kadouri |
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| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | Blood. 104:4260-4260 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Stem cells are intimately associated in-vivo with discrete niches within the 3-dimensional (3-D) bone marrow micro-environment collectively provide molecular signals that mediate their differentiation and self-renewal. A recently developed Plug-Flow Bioreactor System (PluriXTM), which closely mimics the physiological bone marrow environment by combining 3-D stromal cultures with a continuous flow system, is capable of supporting long term maintenance/expansion of transplantable human HSC. The stroma cells, growing inside the PluriXTM bioreactor on porrosive carriers enable the propagation of high density (>100-fold input) 3-D stroma cell cultures for prolonged periods of time. Within 40 days, the number of primary human stroma cells seeded in the bioreactor at a density of 5*104 cells/ml reached 1.5*106 cells/ml and the stroma cell lines reached a density of 5*107–1*108 cells/ml. Three-dimensional static stroma HSC co-cultures were found to be superior to 2-D co-cultures in supporting the maintenance of CB HSC and early hematopoietic progenitors. When cord blood CD34+ cells were seeded on 2-D & 3-D stroma cell static cultures, the 3-D stroma cultures proved superior in supporting the growth of CD34+, CD34+38− and CD34+38−CXCR4+ cells. The 3-D primary human stroma static cultures supported these cells 4.7, 22, 7.4 fold better than the 2-D cultures, respectively. The CD34+ cells seeded on the high-density 3-D stroma cell cultures within the PluriXTM bioreactor demonstrated significant superiority to 2-D and 3-D stroma cell static cultures and 2-D stroma cultures in supporting the growth and expansion of HSC and earlier hematopoietic progenitors. These findings verify that a system based on 3-D stroma co-cultures is preferable for ex-vivo expansion of human HSC’s. The PluriXTM system offers wide-range potential for expansion of stem cells from cord blood and production of specific blood products. |
| Databáze: | OpenAIRE |
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