scholarly journals Infusion of Ex Vivo Expanded Cord Blood Progenitor Cells Is Associated with Reduced Hospital Days and Utilization of Opiate Infusion and Total Parenteral Nutrition in Patients Receiving Myeloablative Cord Blood Transplantation

2015 ◽  
Vol 21 (2) ◽  
pp. S94-S95 ◽  
Author(s):  
Ann Dahlberg ◽  
Filippo Milano ◽  
Colleen Delaney
Keyword(s):  
Parenteral Nutrition ◽  
Cord Blood ◽  
Total Parenteral Nutrition ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Hospital Days

Notch-Mediated Expansion of Human Cord Blood Progenitor Cells Results in Rapid Myeloid Reconstitution in Vivo Following Myeloablative Cord Blood Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 212-212 ◽  
Author(s):  
Colleen Delaney ◽  
Carolyn Brashem- Stein ◽  
Howard Voorhies ◽  
Jonathan Gutman ◽  
Mari Dallas ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Fold Increase ◽  
Short Term ◽  
Post Transplant ◽  
Blood Transplantation ◽  
Cell Fractions

Abstract Delayed hematopoietic recovery following cord blood transplantation (CBT) is thought to result from inadequate numbers of progenitor cells in the graft and is associated with increased early transplant related morbidity and mortality. Using an engineered form of the Notch ligand, Delta1, we have previously reported on novel ex vivo expansion methods for generating greatly increased numbers of human CD34 progenitor cells that repopulate immunodeficient mice with markedly enhanced rate and magnitude. We now report results of the initial 6 patients enrolled in a phase I study evaluating the safety and potential efficacy of cord blood (CB) progenitors cultured in the presence Delta1 and recombinant cytokines, with the goal of generating increased numbers of short term repopulating cells capable of providing rapid myeloid engraftment. These patients (AML, n=5; bi-phenotypic leukemia, n=1), were treated with a myeloablative preparative regimen consists of cytoxan 120mg/kg, fludarabine 75mg/m2 and 1320 cGy TBI, followed one day later by infusion of one non-cultured CB unit and then a second unit that has been CD34 enriched and cultured for 16 days as previously described. The median age and weight of the patients enrolled is 28 years (range 11 to 43) and 61.5 kilograms (range 26 to 76). CB units were selected on the basis of cell dose and a requirement of matching at least 4 of 6 loci with the patient (intermediate resolution for HLA-A and B, and high resolution for HLA-DRB1). The non-cultured unit in all patients was 4/6 matched to the patient. The unit used for expansion was 5/6 matched to the patient in two cases, and 4/6 matched in the other four. After culture, there was an average CD34 fold increase of 160 (range 41 to 382) with an average total nucleated cell (TNC) fold increase of 660 (range 146 to 1496). Average infused TNC/kg x107 was 2.9 (range 1.9–5.8) and 4.6 (range 0.6–9.1) for the non-cultured and cultured cells respectively, and infused CD34 cells/kg (x105) was 2.2 (range 1.1–3.4) and 53.4 (range 9.3–133) respectively. No T cells were generated during culture and no toxicities directly attributable to the cultured product, including infusional or increased acute GVHD, have been observed. All patients have engrafted. Relatively rapid engraftment was observed in 5 out of 6 patients treated to date, with a median time to engraftment of 14 days (range 7 to 34), as compared to 25 days (range 16 to 48) in patients (n=17) undergoing an identical transplant regimen at this center, but with 2 non-cultured CB units. The relative contribution of the expanded and non-cultured grafts over time was determined by a DNA-based assay for short tandem repeat loci on peripheral blood sorted cell fractions to include CD3+, CD33+, CD56+, CD14+ and CD19+ cells, beginning day +7 post transplant. In the 5 patients with early myeloid engraftment (≤20 days), engrafted myeloid cells present at day 7 were derived almost entirely from the expanded unit. In three of these five, ANC >500 was observed at days 7, 9 and 16 and was mainly derived from the expanded unit, whereas in the other 2 patients who achieved ANC>500 at day 13 and 20, myeloid engraftment at day 14 was derived from the non-cultured cells. Persistent contribution to engraftment from the expanded cells has been noted in two patients, one through 280 days post transplant but no longer present at one year, and in a more recently treated patient who is currently 75 days post transplant, the expanded cells continue to dominate in CD33, CD14 and CD56, but not CD3, sorted cell fractions. Furthermore, time to platelet engraftment (>20k) has averaged 30 days (range 19–53). Average follow-up time is 277 days (range 70–632). One patient died on day 462 from complications of VZV myelitis; all other patients are alive and in remission. Overall, accelerated myeloid engraftment has been observed in 5/6 patients treated to date as a direct result of Notch-mediated ex vivo expansion of one of two CB units prior to transplantation with ultimate engraftment from the T replete non-cultured unit. These results further suggest that improvement in early myeloid reconstitution may result from provision of short term repopulating cells and/or of cells able to facilitate engraftment of the non-cultured unit. These studies continue with the goal of achieving consistent, rapid engraftment in recipients of hematopoietic cell transplants to decrease morbidity and mortality in the early post-transplant setting.

scholarly journals Human Application of Ex Vivo Expanded Umbilical Cord-Derived Mesenchymal Stem Cells: Enhance Hematopoiesis after Cord Blood Transplantation

2013 ◽  
Vol 22 (11) ◽  
pp. 2041-2051 ◽  
Author(s):  
Kang-Hsi Wu ◽  
Chris Tsai ◽  
Han-Ping Wu ◽  
Martin Sieber ◽  
Ching-Tien Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Blood Transplantation

scholarly journals Proteomic Profiling ofEx VivoExpanded CD34-Positive Haematopoetic Cells Derived from Umbilical Cord Blood

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Heiner Falkenberg ◽  
Teja Falk Radke ◽  
Gesine Kögler ◽  
Kai Stühler
Keyword(s):  
Cord Blood ◽  
Ex Vivo ◽  
Protein Biosynthesis ◽  
Protein Profile ◽  
Cord Blood Transplantation ◽  
Enrichment Analysis ◽  
Proteomic Profiling ◽  
Blood Transplantation ◽  
Proteome Level ◽  
Proteomic Change

Ex vivoexpansion of haematopoetic cells by application of specific cytokines is one approach to overcome boundaries in cord blood transplantation due to limited numbers of haematopoetic stem cells. While many protocols describe an effective increase of total cell numbers and the amount of CD34-positive cells, it still remains unclear if and how the procedure actually affects the cells’ properties. In the presented publications, CD34-positive cells were isolated from cord blood and expanded for up to 7 days in media supplemented with stem cell factor (SCF), thrombopoietin (THPO), interleukin 6 (IL-6), and fms-related tyrosine kinase 3 ligand (FLT3lg). At days 3 and 7, expanded cells were harvested and analyzed by flow cytometry and quantitative proteomics. 2970 proteins were identified, whereof proteomic analysis showed 440 proteins significantly changed in abundance duringex vivoexpansion. Despite the fact that haematopoetic cells still expressed CD34 on the surface after 3 days, major changes in regard to the protein profile were observed, while further expansion showed less effect on the proteome level. Enrichment analysis of biological processes clearly showed a proteomic change toward a protein biosynthesis phenotype already within the first three days of expression.

scholarly journals FDA-Approved Drug Screening for Compounds That Facilitate Hematopoietic Stem and Progenitor Cells (HSPCs) Expansion in Zebrafish

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2149
Author(s):  
Zhi Feng ◽  
Chenyu Lin ◽  
Limei Tu ◽  
Ming Su ◽  
Chunyu Song ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Drug Repurposing ◽  
Suitable Model ◽  
Dependent Manner ◽  
Blood Disorders ◽  
Hematopoietic Stem ◽  
Blood Transplantation ◽  
Stem And Progenitor Cells

Hematopoietic stem cells (HSCs) are a specialized subset of cells with self-renewal and multilineage differentiation potency, which are essential for their function in bone marrow or umbilical cord blood transplantation to treat blood disorders. Expanding the hematopoietic stem and progenitor cells (HSPCs) ex vivo is essential to understand the HSPCs-based therapies potency. Here, we established a screening system in zebrafish by adopting an FDA-approved drug library to identify candidates that could facilitate HSPC expansion. To date, we have screened 171 drugs of 7 categories, including antibacterial, antineoplastic, glucocorticoid, NSAIDS, vitamins, antidepressant, and antipsychotic drugs. We found 21 drugs that contributed to HSPCs expansion, 32 drugs’ administration caused HSPCs diminishment and 118 drugs’ treatment elicited no effect on HSPCs amplification. Among these drugs, we further investigated the vitamin drugs ergocalciferol and panthenol, taking advantage of their acceptability, limited side-effects, and easy delivery. These two drugs, in particular, efficiently expanded the HSPCs pool in a dose-dependent manner. Their application even mitigated the compromised hematopoiesis in an ikzf1−/− mutant. Taken together, our study implied that the larval zebrafish is a suitable model for drug repurposing of effective molecules (especially those already approved for clinical use) that can facilitate HSPCs expansion.

Sign in / Sign up

Export Citation Format

Share Document