Umbilical cord blood: The promise and the uncertainty

Kindwall‐Keller, Tamila L.; Ballen, Karen K.

doi:10.1002/sctm.19-0288

Cited by 33 publications

(13 citation statements)

References 72 publications

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“…Since the first successful umbilical cord blood transplantation (UCBT) was performed on a 5-year-old boy with Fanconi anemia in 1988 at Hospital Saint-Louis in Paris, France, 4 umbilical cord blood (UCB) has become an available graft source of allo-HSCT for over 30 years, with the advantages of rapid availability, no harm to mothers and donors, low immunogenicity, decreased chronic graft-vs-host disease (GVHD), and low relapse rate in minimal residual disease (MRD). 5,6 Unrelated donor cord blood transplantation (CBT) is an effective and reliable alternative to peripheral blood (PB) or bone marrow (BM) transplant and has emerged as a widely accepted treatment for a wide variety of hematologic diseases such as: acute lymphoblastic leukemia (ALL), [7][8][9] acute myeloid leukemia (AML), [10][11][12] myelodysplastic syndrome (MDS), [13][14][15] and aplastic anemia (AA) [16][17][18] (Table 1). UCB, previously considered medical waste, was suggested as a potential source of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) by Hal Broxmeyer in a private meeting with the late Edward A. Boyse and Judith Bard in 1982.…”

Section: Development Of Umbilical Cord Blood Transplantation In the Past 30 Yearsmentioning

confidence: 99%

“…Since the first successful umbilical cord blood transplantation (UCBT) was performed on a 5‐year‐old boy with Fanconi anemia in 1988 at Hospital Saint‐Louis in Paris, France, 4 umbilical cord blood (UCB) has become an available graft source of allo‐HSCT for over 30 years, with the advantages of rapid availability, no harm to mothers and donors, low immunogenicity, decreased chronic graft‐vs‐host disease (GVHD), and low relapse rate in minimal residual disease (MRD). 5 , 6 …”

Section: Development Of Umbilical Cord Blood Transplantation In the Past 30 Yearsmentioning

confidence: 99%

“…T‐cell depletion in vivo may reduce the risk of GVHD, which in turn increases graft failure and relapse of the primary disease. 6 Relapse remains the major cause of death after transplant. 26 To overcome these challenges, many investigators and clinicians have explored different ways to improve the efficacy of UCBT.…”

Section: Current Challengesmentioning

confidence: 99%

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Umbilical Cord Blood Transplantation: Still Growing and Improving

Zhu

Tang

Sun

2021

Stem Cells Translational Medicine

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Umbilical cord blood transplantation (UCBT) has been performed in the clinic for over 30 years. The biological and immunological characteristics of umbilical cord blood (UCB) have been re-recognized in recent years. UCB, previously considered medical waste, is rich in hematopoietic stem cells (HSCs), which are naïve and more energetic and more easily expanded than other stem cells. UCB has been identified as a reliable source of HSCs for allogeneic hematopoietic stem cell transplantation (allo-HSCT). UCBT has several advantages over other methods, including no harm to mothers and donors, an off-the-shelf product for urgent use, less stringent HLA match, lower incidence and severity of chronic graft-vs-host disease (GVHD), and probably a stronger graft-vs-leukemia effect, especially for minimal residual disease-positive patients before transplant. Recent studies have shown that the outcome of UCBT has been improved and is comparable to other types of allo-HSCT. Currently, UCBT is widely used in malignant, nonmalignant, hematological, congenital and metabolic diseases. The number of UCB banks and transplantation procedures increased exponentially before 2013. However, the number of UCBTs increased steadily in Asia and China but decreased in the United States and Europe year-on-year from 2013 to 2019. In this review, we focus on the development of UCBT over the past 30 years, the challenges it faces and the strategies for future improvement, including increasing UCB numbers, cord blood unit selection, conditioning regimens and GVHD prophylaxis for UCBT, and management of complications of UCBT.

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Section: Development Of Umbilical Cord Blood Transplantation In the Past 30 Yearsmentioning

confidence: 99%

Section: Development Of Umbilical Cord Blood Transplantation In the Past 30 Yearsmentioning

confidence: 99%

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Umbilical Cord Blood Transplantation: Still Growing and Improving

Zhu

Tang

Sun

2021

Stem Cells Translational Medicine

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“…In contrast to peripheral blood stem cell transplantation (PBSCT), UCB has fewer mature T lymphocytes, thus allowing UCB transplantation with a greater degree of HLA mismatch (Stanevsky et al, 2009), and the large number of banked UCB units can easily facilitate the finding of an HLA-matched graft (Mayani et al, 2020). However, the relatively low number of HSPCs present in one UCB unit is a major limitation for UCB transplantation (de Lima et al, 2012;Kindwall-Keller and Ballen, 2020). This is associated with delayed engraftment and higher risk of graft failure, and leads to restriction in their widespread application (Mattsson et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells

Ghebes

Morhayim

Kleijer

et al. 2021

Front. Bioeng. Biotechnol.

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Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we investigate whether primary human bone marrow derived mesenchymal stromal cells (BMSC) EVs isolated from two different origins, fetal (fEV) and adult (aEV) tissue, can increase the relative low number of HSPCs found in umbilical cord blood (UCB) and which EV-derived components are responsible for ex vivo HSPC expansion. Interestingly, aEVs and to a lesser extent fEVs, showed supportive ex vivo expansion capacity of UCB-HSPCs. Taking advantage of the two BMSC sources with different supportive effects, we analyzed the EV cargo and investigated how gene expression is modulated in HSPCs after incubation with aEVs and fEVs. Proteomics analyses of the protein cargo composition of the supportive aEV vs. the less-supportive fEV identified 90% of the Top100 exosome proteins present in the ExoCarta database. Gene Ontology (GO) analyses illustrated that the proteins overrepresented in aEVs were annotated to oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport, or protein folding. In contrast, the proteins overrepresented in fEVs were annotated to extracellular matrix organization positive regulation of cell migration or transforming growth factor beta receptor (TGFBR) signaling pathway. Small RNA sequencing identified different molecular signatures between aEVs and fEVs. Interestingly, the microRNA cluster miR-99b/let-7e/miR-125a, previously identified to increase the number of HSPCs by targeting multiple pro-apoptotic genes, was highly and significantly enriched in aEVs. Although we identified significant differences in the supportive effects of aEVs and fEVs, RNAseq analyses of the 24 h treated HSPCs indicated that a limited set of genes was differentially regulated when compared to cells that were treated with cytokines only. Together, our study provides novel insights into the complex biological role of EVs and illustrates that aEVs and fEVs differentially support ex vivo expansion capacity of UCB-HSPCs. Together opening new means for the application of EVs in the discovery of therapeutics for more efficient ex vivo HSPC expansion.

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“…In this issue of the journal, Kindwall‐Keller and Ballen present a targeted overview of the advantages, disadvantages, and milestones of cord blood transplantation over the past 30 years 1 . First they highlight the advantages of cord blood as a source of donor cells for hematopoietic transplantation, including off the shelf availability, increased tolerance for HLA mismatching, lower incidence of acute and chronic GvHD, lower risk of infectious disease transmission, and improved protection against leukemic relapse in high risk patient populations.…”

mentioning

confidence: 99%

The view for cord blood is “cup half full” not “cup half empty”

Kurtzberg

2020

Stem Cells Translational Medicine

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Ballen present a targeted overview of the advantages, disadvantages, and milestones of cord blood transplantation over the past 30 years. 1 First they highlight the advantages of cord blood as a source of donor cells for hematopoietic transplantation, including off the shelf availability, increased tolerance for HLA mismatching, lower incidence of acute and chronic GvHD, lower risk of infectious disease transmission, and improved protection against leukemic relapse in high risk patient populations.

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Umbilical cord blood: The promise and the uncertainty

Cited by 33 publications

References 72 publications

Umbilical Cord Blood Transplantation: Still Growing and Improving

Umbilical Cord Blood Transplantation: Still Growing and Improving

Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells

The view for cord blood is “cup half full” not “cup half empty”

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