scholarly journals Very Small Embryonic-Like Stem Cells Purified from Umbilical Cord Blood Lack Stem Cell Characteristics

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34899 ◽  
Author(s):  
Ralitza Danova-Alt ◽  
Andreas Heider ◽  
Dietmar Egger ◽  
Michael Cross ◽  
Rüdiger Alt
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood

scholarly journals UMBILICAL CORD BLOOD BANKING IN THE WORLDWIDE HEMATOPOIETIC STEM CELL TRANSPLANTATION SYSTEM: PERSPECTIVES FOR UKRAINE

2017 ◽  
Vol 39 (3) ◽  
pp. 164-170 ◽  
Author(s):  
T O Kalynychenko
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hematopoietic Stem ◽  
Blood Banks ◽  
Cord Blood Banks

Significant progress in the promotion of procedural technologies associated with the transplantation of hematopoietic stem cells caused a rapid increase in activity. The exchange of hematopoietic stem cells for unrelated donor transplantations is now much easier due to the relevant international professional structures and organizations established to support cooperation and standard setting, as well as rules for the functioning of both national donor registries and cord blood banks. These processes are increasing every year and are contributing to the outpacing rates of development in this area. Products within their country should be regulated by the competent government authorities. This study analyzes the work of international and national levels of support for transplantation activity in the field of unrelated hematopoietic stem cell transplantation, the standardization order of technologies, as well as data that justify the need to create a network of donated umbilical cord blood banks in Ukraine as a factor in the development of allogeneic transplantation. This will promote the accessibility of international standards for the treatment of serious diseases for Ukrainian citizens.

scholarly journals A Small-Sized Population of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Shows High Stemness Properties and Therapeutic Benefit

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Miyeon Kim ◽  
Yun Kyung Bae ◽  
Soyoun Um ◽  
Ji Hye Kwon ◽  
Gee-Hye Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Surface Proteins ◽  
Lung Damage ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord

Mesenchymal stem cells (MSCs) represent a promising means to promote tissue regeneration. However, the heterogeneity of MSCs impedes their use for regenerative medicine. Further investigation of this phenotype is required to develop cell therapies with improved clinical efficacy. Here, a small-sized population of human umbilical cord blood-derived MSCs (UCB-MSCs) was isolated using a filter and centrifuge system to analyze its stem cell characteristics. Consequently, this population showed higher cell growth and lower senescence. Additionally, it exhibited diverse stem cell properties including differentiation, stemness, and adhesion, as compared to those of the population before isolation. Using cell surface protein array or sorting analysis, both EGFR and CD49f were identified as markers associated with the small-sized population. Accordingly, suppression of these surface proteins abolished the superior characteristics of this population. Moreover, compared to that with large or nonisolated populations, the small-sized population showed greater therapeutic efficacy by promoting the engraftment potential of infused cells and reducing lung damage in an emphysema mouse model. Therefore, the isolation of this small-sized population of UCB-MSCs could be a simple and effective way to enhance the efficacy of cell therapy.

scholarly journals Intra-Articular Injection of 2 Different Dosages of Autologous and Allogeneic Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells Triggers a Variable Inflammatory Response of the Fetlock Joint on 12 Sound Experimental Horses

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Lélia Bertoni ◽  
Thomas Branly ◽  
Sandrine Jacquet ◽  
Mélanie Desancé ◽  
Loïc Desquilbet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Significant Difference

Osteoarthritis is a significant and costly cause of pain for both humans and horses. The horse has been identified as a suitable model for human osteoarthritis. Regenerative therapy with allogeneic mesenchymal stem cells (MSCs) is a promising treatment, but the safety of this procedure continues to be debated. The aim of this study is to evaluate the safety of intra-articular injections of allogeneic MSCs on healthy joints by comparing two different dosages and two different tissue sources, namely, bone marrow and umbilical cord blood, with a placebo treatment on the same individuals. We also assessed the influence of autologous versus allogeneic cells for bone marrow-derived MSC treatment. Twelve clinically sound horses were subjected to injections in their 4 fetlock joints. Each of the three fetlocks was administered a different MSC type, and the remaining fetlock was injected with phosphate-buffered saline as a control. Six horses received 10 million cells per joint, and the 6 other horses received 20 million cells per joint. Clinical and ultrasound monitoring revealed that allogeneic bone marrow-derived MSCs induced significantly more synovial effusion compared to umbilical cord blood-derived MSCs but no significant difference was noted within the synovial fluid parameters. The administration of 10 million cells in horses triggered significantly more inflammatory signs than the administration of 20 million cells. Mesenchymal stem cell injections induced mild to moderate local inflammatory signs compared to the placebo, with individual variability in the sensitivity to the same line of MSCs. Understanding the behavior of stem cells when injected alone is a step towards the safer use of new strategies in stem cell therapy, where the use of either MSC secretome or MSCs combined with biomaterials could enhance their viability and metabolic activity.

In Vitro and In Vivo Evidence That Umbilical Cord Blood (UCB)-Derived CD45-/SSEA-4+/OCT-4+/CD133+/CXCR4+/Lin- Very Small Embryonic/Epiblast Like Stem Cells (VSELs) Do Not Contain Clonogenic Hematopoietic Progenitors but Are Highly Enriched in More Primitive Stem Cells - Novel View On Hierarchy of UCB Stem Cell Compartment.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 35-35 ◽  
Author(s):  
Ewa K. Zuba-Surma ◽  
Izabela Klich ◽  
Marcin Wysoczynski ◽  
Nicholas J Greco ◽  
Mary J. Laughlin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hematopoietic Stem ◽  
Hematopoietic Activity

Abstract Abstract 35 Recently, we identified in umbilical cord blood (UCB) a population of very small embryonic/epiblast-like (VSEL) stem cells (Leukemia 2007;21:297–303) that are i) smaller than erythrocytes, ii) SSEA-4+/Oct-4+/CD133+/CXCR4+/Lin−/CD45−, iii) respond to SDF-1 gradient and iv) possess large nuclei containing primitive euchromatin. We have demonstrated in vitro that UCB-derived VSELs did not reveal hematopoietic activity freshly after isolation, but grow hematopoietic colonies following co-culture/activation over OP-9 cells. To investigate the hierarchy of UCB-derived, CD45 negative VSELs, we employed staining with Aldefluor - detecting aldehyde dehydrogenase (ALDH), the enzyme expressed in primitive hematopoietic cells. Subsequently, we sorted CD45−/CD133+/ALDHhigh and CD45−/CD133+/ALDHlow sub-fractions of VSELs from UCB samples and established that freshly sorted from UCB VSELs in contrast to sorted CD45+/ CD133+/ALDHhigh and CD45+/CD133+/ALDHlow hematopoietic stem cells (HSC) did not grow colonies in vitro. However, when CD45− VSELs were activated/expanded over OP-9 stroma cells, they exhibit hematopoietic potential and grew in routine methylcellulose cultures hematopoietic colonies composed of CD45+ cells. Interestingly, while CD45−/CD133+/ALDHhigh VSELs gave raise to hematopoietic colonies after the first replating, the formation of colonies by CD45−/CD133+/ALDHlow VSELs was somehow delayed, what suggest that they needed more time to acquire hematopoietic commitment. Thus our in vitro data indicate that both populations of CD45− cells may acquire hematopoietic potential; however hematopoietic specification is delayed for CD45−/CD133+/ALDHlow cells, suggesting their more primitive nature. In parallel, real time PCR analysis confirmed that while freshly isolated CD45−/CD133+/ALDHhigh VSELs express more hematopoietic transcripts (e.g., c-myb, 80.2±27.4 fold difference), CD45−/CD133+/ALDHlow exhibit higher levels of pluripotent stem cell markers (e.g., Oct-4, 119.5±15.5 fold difference as compared to total UCB mononuclear cells) (Figure 1 panel A). Next hematopoietic potential of UCB-derived VSELs was tested in vivo after transplantation into NOD/SCID mice (Figure 1 panel B and C). We noticed that both CD45−/CD133+/ALDHhigh and CD45−/CD133+/ALDHlow VSELs, give rise to human lympho-hematopoietic chimerism in lethally irradiated NOD/SCID mice as assayed 4–6 weeks after transplantation. The level of human hematopoietic CD45+ cells in murine peripheral blood (PB), bone marrow (BM) and spleen (SP) were comparable for both transplanted UCB-VSELs fractions - 7.1±2.9% (PB), 23.2±0.2% (SP) and 25.2±1.0% (BM). In conclusion, our data suggest that freshly isolated very small CD45 negative UCB-VSELs are depleted from clonogeneic progenitors, however they are highly enriched for primitive HSC. Based on our in vitro and in vivo data we postulate following hierarchy of hematopoietic stem cells in UCB (from most primitive to more differentiated) i) CD45−/CD133+/ALDHlow, ii) CD45−/CD133+/ALDHhigh , iii) CD45+/CD133+/ALDHlow and iv) CD45−/CD133+/ALDHhigh. We also postulate that as we have already shown for murine BM-derived VSELs, human UCB-derived CD45 negative VSELs correspond to a population of most primitive long term repopulating HSC (LT-HSC). Of note, we also found that currently employed, routine UCB processing strategies may lead up to ∼50% unwanted loss of these small cells that are endowed with such remarkable hematopoietic activity! Disclosures: No relevant conflicts of interest to declare.

Umbilical Cord Blood Transplantation: A New Alternative Option

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 377-383 ◽  
Author(s):  
William Tse ◽  
Mary J. Laughlin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Hematopoietic Stem Cell ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Alternative Source ◽  
Hematopoietic Stem

Abstract Allogeneic hematopoietic stem cell transplantation is a life-saving procedure for hematopoietic malignancies, marrow failure syndromes, and hereditary immunodeficiency disorders. However, wide application of this procedure is limited by availability of suitably HLA-matched adult donors. Umbilical cord blood (UCB) has being increasingly used as an alternative hematopoietic stem cell source for these patients. To date, over 6000 UCB transplant procedures in children and adults have been performed worldwide using UCB donors. Broader use of UCB for adult patients is however limited by the available infused cell dose. This has prompted intensive research on ex vivo expansion of UCB stem cells and UCB graft-engineering including accessory cells able to improve UCB engraftment and reconstitution and for tissue regenerative potential. Recently, two large European and North American retrospective studies demonstrated that UCB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack HLA-matched adult donors. UCB is anticipated to address needs in both transplantation and regenerative medicine fields. It has advantages of easy procurement, no risk to donors, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite HLA disparity.

scholarly journals Outcome of Sibling's and Unrelated Umbilical Cord Blood Stem Cell Transplantation Combined PBSC in Thalassemia Major and Related Factors Analysis:76 Cases Reported in Single Center

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-19
Author(s):  
Yuhua Xiao ◽  
Xiaoqin Feng ◽  
Yuelin He ◽  
Chunfu Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Stem Cell ◽  
Unrelated Cord Blood

Objectives: At present, allogeneic hematopoietic stem cell transplantation is still the only way to cure thalassemia major (TM) patients. But in fact, less than half of the patients can find matched sibling or unrelated donors.Umbilical cord blood stem cells(UCB) is a potential source of stem cells.This paper was to explore effectiveness and compare the outcomes of sibling's and unrelated cord blood stem cell transplantation combined with PBSC in TM. Methods: From Jan. 2008 to Oct. 2019, the clinical data of 76 children with TM who were first underwent cord blood stem cell transplantation was analyzed retrospectively. As of Dec.31, 2019, the median follow-up time was 53 months. The NF-08-TM protocol with CY + Bu + flu + TT in conditioning, was used for sibling cord blood transplantation(CBT) in which the graft including fresh cord blood and PBSC from newborns. Haploid peripheral blood stem cells combined unrelated cord blood transplantation was carried out with NF-14-TM protocol added CY in day +3, day+ 4 days ,followed infusion of unrelated cord blood in + 6 day.The average infusion of cord blood mononuclear cells was 8.50×10^7 (2.73-20.30×10^7), of which CD34+cells were 2.42×10^5 (0.26-8.06×10^5). Unrelated cord blood mononuclear cells were 5.90×10^7 (0.77-11.35×10^7), of which CD34+ cells were 1.78×10^5 (0.17-4.44×10^5). The number of haploid mononuclear cells was 27.70×10^8 (8.80-63.18×10^8). SPSS 20.0 software was used to analyze the subjects' clinical characteristics, long-term survival rate, factors affecting umbilical cord blood implantation and related complications Results:Total of 45 cases of sibling CBT and 31 cases of unrelated CBT combined with haploid PBSC were enrolled. Two of the 76 thalassemia children died, with an OS of 96.3±2.6%, TFS93.8±3.1%; TMR was 3.7%. The OS of the sibling CBT group and the unrelated CBT group were 97.8 ± 2.2% and 90.0±9.9%, P=0.586; Meanwhile TFS were 93.3 ± 3.7% and 92.9±6.9%, P=0.589. Liver iron concentration (MRI-T2) in the unrelated CBT group was significantly correlated with delayed implantation of stem cells and delayed reconstruction of platelets (P=0.013 and P=0.034).There was no significant difference in the rate of delayed implantation of stem cells and granulocyte reconstruction between the unrelated CBT group and the sibling CBT group, but the rate of delayed platelet reconstruction in the unrelated CBT group was significantly higher than that in the sibling CBT group (P=0.002). The time of umbilical cord blood implantation in the unrelated CBT group was shorter than that in the sibling CBT group (24.32 days vs 37.67 days, P=0.058), but the platelet reconstruction in this group was slower than that in the sibling CBT group, with no statistically significant difference (P=0.061). In the ferritin level, the platelet reconstruction time in the unrelated CBT group was significantly higher than that in the sibling CBT group (P=0.031). Logistic regression analysis showed that ferrimin, umbilical cord blood sources, dose of umbilical cord blood mononuclear cells and acute GVHD were not risk factors for delayed implantation of stem cells (over 30 days).The incidence of acute and chronic GVHD in the unrelated CBT group was significantly higher than that in the sibling CBT group (P < 0.001 and P=0.034). The virus infection rate of the unrelated CBT group was significantly higher than that of the sibling CBT group (P=0.008). The infection of herpes simplex virus type I was common in sibling CBT, while cytomegalovirus was the main infectious virus in unrelated CBT. Conclusion:By increasing the dose of stem cells, the outcomes of TM after transplantation was favorable both in sibling and unrelated CBT group. Unrelated CBT combined with haploid PBSC can potentially reduce implantation time compared with sibling CBT. The strategies of prophylaxis and treatment of GVHD and cytomegalovirus infection should be strengthened. Iron overload may affect umbilical cord blood stem cell implantation and hematopoietic recovery. Figure 1 Disclosures No relevant conflicts of interest to declare.

CELLULAR AND MOLECULAR EVALUATION OF IN VITRO QUALITY PARAMETERS OF HUMAN UMBILICAL CORD BLOOD-DERIVED MESENCHYMAL STEM CELLS

2021 ◽  
pp. 52-54
Author(s):  
Sara Jabeen ◽  
Usha Gupta ◽  
Aleem Ahmed Khan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Stem Cell Markers ◽  
Number Of Cells

Introduction: Establishing a reproducible adult stem cell culture system, such as mesenchymal stem cells (MSCs), is critical for elucidating the function of molecular markers associated with these cells' undifferentiated state. In this study, we describe some important parameters to be considered for a successful isolation, culture, and characterization of MSCs from human umbilical cord blood (hUCB). Methods: Five hUCB samples were collected from healthy female subjects who were free from infectious diseases and genetic disorders. Mononuclear cells (MNCs) were counted, and viability was determined using MTT assay. MNCs were cultured in DMEM supplemented with 10% fetal bovine serum and enriched through culture and characterized using morphometric, and molecular analysis. Results: The minimum number of cells was 12.5 million and highest number of cells was 20.6 million from all ve samples. In initial culture of MSCs from hUCB, various morphologic phenotypes were seen, although the cells eventually developed a homogeneous broblast-like shape at day 14 showing >80% conuency. Spindle-shaped clonogenic MSCs expressed a high level of CD90, CD105, and CD73, while negative expression of CD34. Our study provided evidence of expansion of enriched MSCs in culture from day 1 to day 21 as supported by data of CD90, CD105 and CD73 expression levels in a time-dependent manner. Conclusion: Our results suggest that the expanded hUCB harbor an enriched source of MSCs that express pluripotent stem cell markers and lack hematopoietic markers after culture and forms the basis for using hUCB as eminent source of MSCs, which can be used for different therapeutic applications.

Effect of Umbilical Cord Blood Hematopoietic Stem Cells on Formation of Angiogenic Structures.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4054-4054
Author(s):  
Aaron Victor ◽  
Mary J. Laughlin ◽  
Marcie R. Finney ◽  
Nicholas J. Greco
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Coronary Artery ◽  
Hematopoietic Stem Cells ◽  
Cord Blood ◽  
Hematopoietic Stem Cell ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hematopoietic Stem

Abstract There is a significant unmet need for novel therapeutic treatments for patients presenting with chronic ischemic conditions such as coronary artery disease and diabetes. Revascularization measures, such as infusions with endothelial progenitor cells (EPC) characterized by the expression of early hematopoietic stem cell markers, hold significant potential in treating these patients. Pre-clinical and clinical studies using transplanted EPC to restore blood flow and improve cardiac function in animal models of ischemia have proven effective. Recent studies have used bone marrow mononuclear cells while some more recent studies have focused on enriched stem cell treatments, such as purified bone marrow hematopoietic stem cell (HSC) CD34+/133+ cell populations, in patients with coronary artery ischemia. In this study, the hypothesis to be tested was that umbilical cord blood-derived hematopoietic stem cells (CD34+/CD133+) cells may augment the formation and stability of angiogenic networks of cord-like structures derived from umbilical vein endothelial cells (HUVEC) cultured in growth factor-reduced Matrigel (GFR MG) assays. Umbilical cord blood MNC were isolated with ficoll and separated into HSC CD34+/133+ and CD34−/133− fractions. Positive fractions were flow cytometry, sorted for HSC, and stained with the lipophilic fluorescent red dye CM-DiI and the HUVEC were stained with the lipophilic fluorescent green dye Oregon Green. HUVEC alone or HSC and HUVEC were then co-cultured under hypoxic conditions (1% O2) on the GFR MG in 96 well plates. Cells were photographed with a fluorescent microscope at 16, 48, and 72 hours. Transwell experiments (0.4μm pores) were also performed with HSC CD34+/133+ and CD34−/133− fractions prepared and suspended in transwells above HUVEC plated on GFR MG on bottom wells. The presence of both HSC CD34+/133+ and CD34−/133− fractions increased the numbers of nodes (branch points of structures) and allowed the structures to persist when observed over three days (a representative experiment of N =3) (Table): Day 1 Day 1 Day 2 Day 2 Day 3 Day 3 Node # % Total Node # % Total Node # % Total HUVEC 11.6 ± 4.9 100 1.3 ± 1.2 9.2 0.33 ± 0.58 2.2 HUVEC + HSC CD34+/133+ 17.3 ± 9.2 100 6.3 ± 4.5 35.3 4.7 ± 5.5 21.4 HUVEC + HSC CD34−/133− 34 ± 13.2 100 19.7 ± 2.5 61.6 10 ± 3.6 29.8 The HSC CD34−/133− fraction resulted in a greater increase in node formation than the HSC CD34+/133+ and both fractions stimulated significant persistence in formed structures. In addition, CM-Dil labeled cells were localized at nodes points. Results with the transwell assay demonstrated that when either HSC CD34+/133+ or CD34−/133− fractions were suspended above HUVEC, augmentation of the formation of cord-like structures was not observed. In summary, both umbilical cord blood-derived HSC CD34+/133+ and CD34−/133− fractions possess properties that augment the formation of angiogenic structures. We observed that the number of nodes are greater in the presence of both HSC CD34+/133+ and CD34−/133− fractions than with HUVEC alone. The transwell experiment suggested that cell-to-cell interactions are necessary for augmentation of the cord structures. In future studies, we will address the mechanism of intercellular interactions that result in the augmentation of cord-like structures and which particular subpopulations within cord blood, both from HSC CD34+/133+ and CD34−/133− fractions are required for augmentation of structure formation.

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