In vitro expansion of hematopoietic cells finds many applications in the clinic. This technique has been useful in expanding CD34+ cells for transplantation/re infusion, although most of the technology has consisted of small scale static cultures in which there is variable CFUGM expansions and failure to maintain LTC IC (long term culture initiating cells). The Investigators have found that perfusion cultures of bone marrow mononuclear cells result in expansion not only of the CD34+ cells and CFU GM but also the 5 week and 8 week LTC IC. In this application the Investigators purpose developing a perfusion system for expanding CD34 enriched cell populations including the LTC IC cell population. They propose to assess the effects of medium perfusion and pre formed stroma upon this expansion, and will use the stroma containing systems as a model and bench mark for ultimately developing stromal free systems based entirely upon a defined spectrum of exogenously added growth factors. If successful, these studies will lead to a Phase II proposal for the development of automated systems for expansion of purified cell populations and subsequent clinical trials to establish the efficacy of the expanded cells.
| Koller, M R; Oxender, M; Jensen, T C et al. (1999) Direct contact between CD34+lin- cells and stroma induces a soluble activity that specifically increases primitive hematopoietic cell production. Exp Hematol 27:734-41 |
| Koller, M R; Manchel, I; Brott, D A et al. (1996) Donor-to-donor variability in the expansion potential of human bone marrow cells is reduced by accessory cells but not by soluble growth factors. Exp Hematol 24:1484-93 |
