Is in vitro expansion of human cord blood cells clinically relevant?

Abstract

Summary:cells such as long-term culture-initiating cells (LTC-IC) may be required to overcome slow initial peripheral blood recovery in adult recipients. For these reasons we have Peripheral blood recovery after cord blood (CB) transplantation is delayed compared with marrow. Expaninvestigated in vitro expansion of CB cells. Experiments culturing unseparated CB or mononuclear sion of CB haemopoietic cells has been investigated with the aim of reducing cytopenia following transplantation.cells ( In this study we cultured enriched CB CD34 + cells for 14 days in the presence of IL-3, IL-6, G-CSF, GM-CSF to an untreated donation. Combined with in vivo posttransplant growth factor therapy this could prompt and SCF. Expansion of total cells, CFC and LTC-IC was calculated together with flow cytometric analysis to follow early peripheral blood recovery after CB transplantation, without significant loss of LTC-IC or donor the changes in CD38 and HLA-DR expression of the CD34 + cells during culture. lymphocytes. Keywords: cord blood; CD34 + ; colony-forming cells;Finally, from a practical point of view, clinical expansion of CB cells will require the manipulation and culture of CB LTC-IC; expansion following cryopreservation and it is essential that any cell losses are taken into account when the true benefit of expansion culture in clinical transplantation is being Cord blood (CB) transplants in children are characterized assessed. by slow recovery of neutrophils and to a greater extent platelets, 1 suggesting that progenitor cell numbers in the donation are limiting. Despite limited progenitor numbers sufficient marrow repopulating cells are present, as susMaterials and methods tained engraftment in children has been documented. 2 These data suggest in vitro expansion of relatively well differentiated progenitors will enhance peripheral blood recovCord blood collection ery following CB transplantation. We hypothesise that sufficient marrow repopulating cells are also available for Umbilical CB samples were collected by gravity into sterile reliable engraftment in adult recipients. However, expan-50 ml tubes containing 1000 IU heparin after the umbilical sion of post-progenitor cells, progenitor cells and primitive cord had been clamped and cut by the midwife. All samples were from normal full-term deliveries. Cord blood collection had local hospital ethics committee approval and time entirely at the discretion of the midwife.

Multicentre European study comparing selection techniques for the isolation of CD34+ cells

“…31,32 All centres using the MiniMACS columns obtained good yields in agreement with the findings of other investigators. 12,[28][29][30]33,34 Though yields from Dynabeads and the Ceprate columns varied widely, those of the Ceprate columns were within the range reported in other studies. 29,33,35 Low yields may be a result of poor mechanical separation where cells are lost, or lack of expertise with particular techniques, and will affect both yield and final product purity.…”

“…Mechanisms involved in control of proliferation, differentiation, malignant transformation and gene transfection can be studied and culture conditions optimized for ex vivo expansion to generate appropriate numbers of cells required for transplantation. [9][10][11][12] Extensive amplification and self-renewal of primitive cells such as LTC-IC have been reported and more recently megakaryocyte precursors generated from CD34 + cells were safely administered to PBPC transplant recipients. [13][14][15][16] Renewed interest in immunotherapy coupled with the ability to generate dendritic cells from CD34 + cells has resulted in a variety of protocols to obtain dendritic cells for transplantation or vaccination.…”

Long-term culture-initiating cells (LTC-IC) produced from CD34+ cord blood cells with limiting dilution method

“…Although the number of articles on cord blood LTC-IC are somewhat limited, our LTC-IC/CD34+ cell numbers were lower compared to some of the published studies [13,14], but results of several studies were consistent with ours [15]. There are several controversial issues, which will be discussed in the remainder of this article.…”

Bigger is better: maternal and neonatal predictors of hematopoietic potential of umbilical cord blood units

“…10,11 Expansion of cord blood cells, after culturing with cytokine combinations, is being studied as a method of increasing the progenitor cells, but is still work in progress. 21,22 Our analysis is descriptive and represents the largest series of its kind, and the first to study birth order and gesBone Marrow Transplantation tational age. The parameters tested, CFU-GM, CD34…”