Engraftment kinetics of human CD34+ cells from cord blood and mobilized peripheral blood co-transplanted into NOD/SCID mice

Ramı́rez, Manuel; Regidor, C; Marugán, Isabel; Garcı́a-Conde, J; Bueren, Juan A.; Fernández, Maribel

doi:10.1038/sj.bmt.1704765

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…To test the capacity for competitive engraftment of these two sources of HSC, a fixed number of positively selected CD34 + cells from UCB and different numbers of CD34 + MHSC were co‐infused to SCID‐NOD mice. Our data showed greater potential of human UCB cells for competitive sustained engraftment in the xenogeneic model used that was only abrogated by the co‐infusion of very large numbers of MHSC cells (Ramírez et al , 2005).…”

Section: General Perspective Of Unrelated Ucbt As a Modality Of mentioning

confidence: 85%

Improving the outcome of cord blood transplantation: use of mobilized HSC and other cells from third party donors

Fernández

2009

Br J Haematol

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SummaryWe developed the strategy of umbilical cord blood transplants (UCBT) with co-infusion of a limited number of highly purified mobilized haematopoietic stem cells (MHSC) from a human leucocyte antigen (HLA) unrestricted third party donor (TPD). Short post-transplant periods of neutropenia were usually observed in adults with haematological neoplasms receiving UCBT with a relatively low cell content and 0-3 HLA mismatches after myeloablative conditioning. This resulted from an early and initially predominant engraftment of the TPD-MHSC. After a variable period of double complete TPD + UCB chimerism, final full UCB chimerism was achieved (cumulative incidence >90%) within 100 d. Early recovery of the circulating neutrophils resulting from the 'bridge transplant' of the TPD-MHSC reduced the incidence of serious neutropenia-related infections, also facilitating the use of drugs with myelosuppressive side effects to combat other infections. The observed incidence of graft-versus-host disease and relapses was low, with overall and disease-free survival curves comparable to those of HLA identical sibling transplants. Post-transplant recovery of natural killer cells occurred soon after the transplant and B cells recovered around 6 months, but T-cell recovery took more than 1 year. Available data show that T cell recovery derives from UCB-HSC through thymic differentiation and that cytomegalovirus (CMV)-specific lymphocytes develop following CMV reactivations.

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Section: General Perspective Of Unrelated Ucbt As a Modality Of mentioning

confidence: 85%

Improving the outcome of cord blood transplantation: use of mobilized HSC and other cells from third party donors

Fernández

2009

Br J Haematol

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“…Only for xenotransplantation experiments (see below), CD34 + cells were isolated from umbilical cord blood (UCB), based on the higher in vivo engraftment ability compared with adult CD34 + cells . Ten fresh UCB units were either purchased from the Barcelona Blood and Tissue Bank and CHEMCYL or kindly provided by the Obstetrics Department of Hospital Universitario de Salamanca following standard procedures, after proper informed consent was obtained from the corresponding mothers.…”

Section: Methodsmentioning

confidence: 99%

The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability

et al. 2019

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Mesenchymal stromal cells (MSC) may exert their functions by the release of extracellular vesicles (EV). Our aim was to analyze changes induced in CD34 + cells after the incorporation of MSC-EV. MSC-EV were characterized by flow cytometry (FC), Western blot, electron microscopy, and nanoparticle tracking analysis. EV incorporation into CD34 + cells was confirmed by FC and confocal microscopy, and then reverse transcription polymerase chain reaction and arrays were performed in modified CD34 + cells. Apoptosis and cell cycle were also evaluated by FC, phosphorylation of signal activator of transcription 5 (STAT5) by WES Simple, and clonal growth by clonogenic assays. Human engraftment was analyzed 4 weeks after CD34 + cell transplantation in nonobese diabetic/severe combined immunodeficient mice. Our results showed that MSC-EV incorporation induced a downregulation of proapoptotic genes, an overexpression of genes involved in colony formation, and an activation of the Janus kinase (JAK)-STAT pathway in CD34 + cells. A significant decrease in apoptosis and an increased CD44 expression were confirmed by FC, and increased levels of phospho-STAT5 were confirmed by WES Simple in CD34 + cells with MSC-EV. In addition, these cells displayed a higher colony-forming unit granulocyte/macrophage clonogenic potential. Finally, the in vivo bone marrow lodging ability of human CD34 + cells with MSC-EV was significantly increased in the injected femurs. In summary, the incorporation of MSC-EV induces genomic and functional changes in CD34 + cells, increasing their clonogenic capacity and their bone marrow lodging ability. STEM CELLS 2019;37:1357-1368 SIGNIFICANCE STATEMENTIn the current study, the authors validate for the first time that preincubating human CD34 + cells with extracellular vesicles derived from human mesenchymal stromal cells not only modifies the gene expression of the recipient cells (inducing a downregulation of proapoptotic genes and overexpression of genes involved in colony formation and JAK-STAT pathway) but also significantly increases their in vitro clonogenic ability and, most importantly, increases their 4-week bone marrow lodging ability in vivo in a standard xenotransplantation model. This strategy could potentially be exploited to increase the hematopoietic engraftment in the clinical setting.

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“… 17 , 34 The differing cell counts in the UCB units and haploidentical grafts might also contribute to different outcomes. 35 …”

Section: Discussionmentioning

confidence: 99%

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial

Zhou,

Chen,

Liu

et al. 2024

Sig Transduct Target Ther

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AbstractsCoinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18–60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75–46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7–87.9 vs. 67.8% 95% CI 60.0–76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6–78.8 vs. 57.6%, 95% CI 49.6–67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0–12.2 vs. 30.3%, 95% CI 30.1–30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3–4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.

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Engraftment kinetics of human CD34+ cells from cord blood and mobilized peripheral blood co-transplanted into NOD/SCID mice

Cited by 9 publications

References 20 publications

Improving the outcome of cord blood transplantation: use of mobilized HSC and other cells from third party donors

Improving the outcome of cord blood transplantation: use of mobilized HSC and other cells from third party donors

The Incorporation of Extracellular Vesicles from Mesenchymal Stromal Cells Into CD34+ Cells Increases Their Clonogenic Capacity and Bone Marrow Lodging Ability

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial

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