Expansion of LTC‐ICs and Maintenance of p21 and BCL‐2 Expression in Cord Blood CD34 + /CD38 − Early Progenitors Cultured over Human MSCs as a Feeder Layer
Open Access
- 1 November 2002
- journal article
- research article
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 20 (6), 573-582
- https://doi.org/10.1634/stemcells.20-6-573
Abstract
Allogeneic transplantation with umbilical cord blood (UCB) is limited in adult recipients by a low CD34+ cell dose. Clinical trials incorporating cytokine‐based UCB in vitro expansion have not demonstrated significant shortening of hematologic recovery despite substantial increases in CD34+ cell dose, suggesting loss of stem cell function. To sustain stem cell function during cytokine‐based in vitro expansion, a feeder layer of human mesenchymal stem cells (MSCs) was incorporated in an attempt to mimic the stem cell niche in the marrow microenvironment. UCB expansion on MSCs resulted in a 7.7‐fold increase in total LTC‐IC output and a 3.8‐fold increase of total early CD34+ progenitors (CD38−/HLA‐DR−). Importantly, early CD34+/CD38−/HLA‐DR− progenitors from cultures expanded on MSCs demonstrated higher cytoplasmic expression of the cell‐cycle inhibitor, p21cip1/waf1, and the antiapoptotic protein, BCL‐2, compared with UCB expanded in cytokines alone, suggesting improved maintenance of stem cell function in the presence of MSCs. Moreover, the presence of MSCs did not elicit UCB lymphocyte activation. Taken together, these results strongly suggest that the addition of MSCs as a feeder layer provides improved conditions for expansion of early UCB CD34+/CD38−/HLA‐DR− hematopoietic progenitors and may serve to inhibit their differentiation and rates of apoptosis during short‐term in vitro expansion.Keywords
This publication has 34 references indexed in Scilit:
- Survival and Cell Cycle Control in Early Hematopoiesis: Role of Bcl-2, and the Cyclin Dependent Kinase Inhibitors P27 and P21Leukemia & Lymphoma, 2002
- Stem Cell Self-Renewal Specified by JAK-STAT Activation in Response to a Support Cell CueScience, 2001
- A Niche Maintaining Germ Line Stem Cells in the Drosophila OvaryScience, 2000
- Murine Stromal Cell Line HESS‐5 Maintains Reconstituting Ability of Ex Vivo‐Generated Hematopoietic Stem Cells from Human Bone Marrow and Cytokine‐Mobilized Peripheral BloodThe International Journal of Cell Cloning, 2000
- Prompt and durable engraftment in two older adult patients with high risk chronic myelogenous leukemia (CML) using ex vivo expanded and unmanipulated unrelated umbilical cord bloodBone Marrow Transplantation, 2000
- Simultaneous cord blood transplantation of ex vivo expanded together with non-expanded cells for high risk leukemiaBone Marrow Transplantation, 1999
- Clinical-scale human umbilical cord blood cell expansion in a novel automated perfusion culture systemBone Marrow Transplantation, 1998
- Placental Blood as a Source of Hematopoietic Stem Cells for Transplantation into Unrelated RecipientsNew England Journal of Medicine, 1996
- Mesenchymal stem cellsJournal of Orthopaedic Research, 1991
- LIF: a molecule with divergent actions on myeloid leukaemic cells and embryonic stem cellsReproduction, Fertility and Development, 1989