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- Nilsson, Anders K., 1982, et al.
(författare)
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The proteome signature of cord blood plasma with high hematopoietic stem and progenitor cell count
- 2022
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Ingår i: Stem Cell Research. - : Elsevier BV. - 1873-5061. ; 61
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem and progenitor cells (HSPC) from umbilical cord blood (UCB) are used for transplantation to treat blood disorders. Methods to estimate the HSPC count in umbilical cord blood, and thereby identify high-value blood units, are time-consuming and costly. Recent studies indicate that the UCB plasma protein composition relates to the HSPC count. We compared the plasma proteome of UCB with high vs low HSPC cell count (> 115 x 10(6) vs < 51 x 10(6) CD34(+) cells l(-1)) by using a combination of global untargeted MS quantitative proteomics and targeted proximity extension assay (PEA) proteomics. For the MS platform, 96 proteins differed significantly between the CD34(+) groups, and out of these, 44 proteins showed more than a two-fold difference. Seven pathways were enriched in high CD34(+) samples, including pathways relating to platelets, coagulation, and lipid transport. For the PEA platform, 61 proteins were differentially abundant, and among these 7 proteins showed more than a two-fold difference between groups. In the PEA data, a high CD34(+) cell count was associated with a protein hub with functions in platelet degranulation. We conclude that the HSPC count is related to the UCB plasma proteome, but that further studies are needed to discern if these findings reflect causal relationships.
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| 2. |
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| 3. |
- Frändberg, Sofia, 1972, et al.
(författare)
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Concentration of the CDCP1 protein in human cord plasma may serve as a predictor of hematopoietic stem and progenitor cell content
- 2018
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Ingår i: Stem Cell Research. - : Elsevier BV. - 1873-5061. ; 29, s. 24-27
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Tidskriftsartikel (refereegranskat)abstract
- Successful hematopoietic stem and progenitor cell (HSPC) transplantation rests upon reliable methods for their enumeration in sources such as cord blood (CB). Methods used today are costly, time consuming and exhaust the limited number of cells needed for transplantation. The aim of this study was to analyze if surplus plasma from CB contains biomarkers that can predict HSPC content in CB. Frozen, surplus plasma from 95 CB units was divided into two groups based on CD34+ cell concentration. Birth weight, gestation age, gender, mode of delivery, collection volume, nucleated cell count and colony forming unit assay results were available. Samples were analyzed with a proximity ligation assay covering 92 different proteins. Two-group t-test with p-values adjusted for false discovery rate (FDR) identified 5 proteins that significantly differed between the two groups. CDCP1 was the most significant (FDR adjusted p-value 0.006). Correlation with CDCP1 concentration was most significant for CD34+ concentration and nucleated cell count. Multivariate analysis showed that CD34 and gender seemed to influence the level of CDCP1. In conclusion, CDCP1 was identified as a potential biomarker of HSPC content in CB. The finding also warrants further investigation for a possible role of CDCP1 in regulating HSPC presence in CB. © 2018
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| 4. |
- Frändberg, Sofia, 1972
(författare)
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Exploring the heterogeneity of the hematopoietic stem and progenitor cell pool in cord blood
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hematopoietic stem cell transplantation (HSCT) is a curative treatment for a wide range of malignant and hereditary disorders. It is yet the only clinically established stem cell treatment. Hematopoietic stem and progenitor cells (HSPC) can be harvest-ed from bone marrow (BM), stimulated peripheral blood (PBSC) or umbilical cord blood (CB) collected from the placenta after clamping of the cord. A critical factor for the success of HSCT is the dose of functioning HSPC the recipient receives. The Na-tional Swedish Cord Blood Bank (NSCBB) was founded in 2005. We compiled the achievements of the NSCBB and investigated the impact of a change of practices from early to delayed clamping on CB collection volume and nucleated cell number. We developed novel methods using flow cytometry for measurement of functional HSPC in CB, firstly for the simultaneous definition of the Hoechst Side Population (SP), Aldehyde Dehydrogenase activity (ALDH) and the expression of the surface protein CD34 and secondly for the definition of viable and apoptotic cells in the ALDH and CD34 positive populations respectively. Finally, we screened for bi-omarkers in CB plasma that may predict the HSPC content in the corresponding CB collection using a multiplex immunoassay. The NSCBB stands up well in international comparison and the implementation of delayed clamping had no major effect on collection efficiency. There was no overlap between the SP and the ALDH popula-tions, suggesting that they define HSPC pools with different properties. Few apoptotic cells were identified in the ALDH population compared to the viable CD34 positive population, indicating that the ALDH assay intrinsically excludes apoptotic cells. We identified the CDCP-1 protein as a possible biomarker for HSPC content in CB.
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| 6. |
- Frändberg, Sofia, 1972, et al.
(författare)
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High quality cord blood banking is feasible with delayed clamping practices. The eight-year experience and current status of the national Swedish Cord Blood Bank.
- 2016
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Ingår i: Cell and tissue banking. - : Springer Science and Business Media LLC. - 1573-6814 .- 1389-9333. ; 17:3, s. 439-48
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Tidskriftsartikel (refereegranskat)abstract
- The National Swedish Cord Blood Bank (NS-CBB) is altruistic and publicly funded. Herein we describe the status of the bank and the impact of delayed versus early clamping on cell number and volume. Cord Blood Units (CBUs) were collected at two University Hospitals in Sweden. Collected volume and nucleated cell content (TNC) were investigated in 146 consecutive Cord Blood (CB) collections sampled during the first quarter of 2012 and in 162 consecutive CB collections done in the first quarter of 2013, before and after clamping practices were changed from immediate to late (60s) clamping. NS-CBB now holds close to 5000 units whereof 30% are from non-Caucasian or mixed origins. Delayed clamping had no major effect on collection efficiency. The volume collected was slightly reduced (mean difference, 8.1ml; 95% CI, 1.3-15.0ml; p=0.02), while cell recovery was not (p=0.1). The proportion of CBUs that met initial total TNC banking criteria was 60% using a TNC threshold of 12.5 × 10(8), and 47% using a threshold of 15 × 10(8) for the early clamping group and 52 and 37% in the late clamping group. Following implementation of delayed clamping practices at NS-CBB; close to 40% of the collections in the late clamping group still met the high TNC banking threshold and were eligible for banking, implicating that that cord blood banking is feasible with delayed clamping practices.
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| 7. |
- Frändberg, Sofia, 1972, et al.
(författare)
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The aldehyde dehydrogenase cord blood potency assay excludes early apoptotic cells
- 2018
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 58:6, s. 1452-1457
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDCord blood units (CBUs) are processed, frozen, and thawed before use in hematopoietic stem cell (HSC) transplantation. The manipulations affect HSC functionality, that is, induce apoptosis and reduce viability. HSC content, commonly expressed as CBU potency, that is, the expected ability of a CBU to restore hematopoiesis, is traditionally approximated through viable CD34+ cells and the colony-forming unit (CFU) cell cultivation assay. Alternative approaches, for example, the aldehyde dehydrogenase (ALDH) enzyme-based assay, are also forthcoming. We hypothesized that the ALDH assay might exclude apoptotic cells since it is based on enzyme activity. To investigate this, we designed a protocol for simultaneous staining of viable and apoptotic CD34+ and ALDH+ cells using 7-aminoactinomycin (7-AAD) and annexin V, in frozen-thawed CBUs. Results were correlated with results from the colony-forming unit-granulocyte/macrophage (CFU-GM) assay. STUDY DESIGN AND METHODSSamples from 57 CBUs were thawed and simultaneously analyzed for CD34+ cells, ALDH+ cells, viability (7-AAD), and apoptosis (annexin V) using flow cytometry. Enumeration of CFUs was also performed. RESULTSNo nonviable and few apoptotic cells (mean 0.7%) were identified in the ALDH+ population compared to the viable CD34+ population (mean 3.6%). The total number of ALDH+ cells correlated better than viable CD34+ cells (r=0. 72 vs. r=0.66; p<0.0001) with the results of the CFU assay. CONCLUSIONThe ALDH assay excludes nonviable and apoptotic cells, and therefore correlates better with CFU enumeration compared to the number of viable CD34+ cells. We propose that the ALDH assay might replace the CFU-GM method in CBU potency measurements.
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