scholarly journals Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia

2021 ◽  
Vol 9 ◽  
Author(s):  
Jia Chen ◽  
Yuhan Chen ◽  
Xue Du ◽  
Guojun Liu ◽  
Xiaowei Fei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Bronchopulmonary Dysplasia ◽  
Noncoding Rna ◽  
Mononuclear Cells ◽  
Gene Set Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pulmonary Vessel ◽  
Cerna Network

Bronchopulmonary dysplasia (BPD) is a common pulmonary complication observed in preterm infants that is composed of multifactorial pathogenesis. Current strategies, albeit successful in moderately reducing morbidity and mortality of BPD, failed to draw overall satisfactory conclusion. Here, using a typical mouse model mimicking hallmarks of BPD, we revealed that both cord blood-derived mononuclear cells (CB-MNCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) are efficient in alleviating BPD. Notably, infusion of CB-MNCs has more prominent effects in preventing alveolar simplification and pulmonary vessel loss, restoring pulmonary respiratory functions and balancing inflammatory responses. To further elucidate the underlying mechanisms within the divergent therapeutic effects of UC-MSC and CB-MNC, we systematically investigated the long noncoding RNA (lncRNA)–microRNA (miRNA)–messenger RNA (mRNA) and circular RNA (circRNA)–miRNA–mRNA networks by whole-transcriptome sequencing. Importantly, pathway analysis integrating Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)/gene set enrichment analysis (GSEA) method indicates that the competing endogenous RNA (ceRNA) network is mainly related to the regulation of GTPase activity (GO: 0043087), extracellular signal-regulated kinase 1 (ERK1) and ERK2 signal cascade (GO: 0070371), chromosome regulation (GO: 0007059), and cell cycle control (GO: 0044770). Through rigorous selection of the lncRNA/circRNA-based ceRNA network, we demonstrated that the hub genes reside in UC-MSC- and CB-MNC-infused networks directed to the function of cell adhesion, motor transportation (Cdk13, Lrrn2), immune homeostasis balance, and autophagy (Homer3, Prkcd) relatively. Our studies illustrate the first comprehensive mRNA–miRNA–lncRNA and mRNA–miRNA–circRNA networks in stem cell-infused BPD model, which will be valuable in identifying reliable biomarkers or therapeutic targets for BPD pathogenesis and shed new light in the priming and conditioning of UC-MSCs or CB-MNCs in the treatment of neonatal lung injury.

Optimization of Isolation and Further Molecular and Functional Characterization of SSEA-4+/Oct-4+/CD133+/CXCR4+/LINneg/CD45neg Very Small Embryonic-Like (VSEL) Stem Cells Isolated from Umbilical Cord Blood.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2316-2316 ◽  
Author(s):  
Ewa K Zuba-Surma ◽  
Magdalena Kucia ◽  
Izabela Klich ◽  
Nicholas Greco ◽  
Mary L Laughlin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Mononuclear Cells ◽  
Functional Characterization ◽  
Molecular Techniques ◽  
Volume Reduction ◽  
Volume Depletion ◽  
Vaginal Deliveries

Abstract Several lines of evidence support the hypothesis that pluripotent stem cells (PSCs) reside in human tissues. Recently, we identified a population of very small embryonic-like (VSEL) SCs in umbilical cord blood (CB) (Leukemia2007;21:297-303). These VSELs are: i) very small in size (<6 um); ii) SSEA-4+/Oct-4+/CD133+/CD34+/CXCR4+/Linneg/ CD45neg; iii) responsive to a stromal derived factor (SDF)-1 gradient; and iv) possess large nuclei that contain primitive euchromatin. In the current study, we optimized their isolation/purification strategy and employed several imaging and molecular techniques to better analyze these primitive cells. We noticed that because of their small size, CD133+/ Linneg/CD45neg VSELs are lost (42.5±12.6%) during routine CB unit processing by volume depletion before storage/freezing. Interestingly, these cells are more resistant to changes following freezing and thawing as compared to normal hematopoietic (H)SCs. Interestingly, 82.7±17.3% of the initially frozen CD133+/Linneg/CD45neg VSELs are preserved in frozen CB units, while only 65.0±6.1% CD133+/Linneg/CD45neg HSCs are recovered. Furthermore, when we employed Ficoll centrifugation to purify CB mononuclear cells (CB MNCs), we found that while 59.8±7.2% of CD133+/Linneg/CD45neg VSELs were lost, their hematopoietic counterparts (CD133+/Linneg/CD45+) were almost fully recovered (Fig. 1A). These data indicate that other more “VSEL-saving” strategies of erythrocyte depletion should be developed because of the unusual size and density of these cells. We also established that the most the optimal “VSEL-saving” strategy to deplete erythrocytes from CB was hypotonic lysis. However, we noticed that during this procedure, lyzed erythrocytes release phosphatidyloserine positive (PS+) membrane-derived microvesicles (MVs) and these PS+ MVs preferentially bind to VSELs. Because of this phenomenon, VSELs become PS+ and may be falsely recognized as apoptotic cells in the Annexin-V-binding assay. The unique morphological features of VSELs were confirmed by several complementary imaging methods. ImageStream analysis revealed that VSELs are smaller than erythrocytes, are larger than platelets, and posses a high nuclear/cytoplasmic ratio (Fig. 1B). The fraction of CD133+/Linneg/CD45neg) VSELs with the smallest size (<6 um) exhibit a high cytoplasmic nuclear ratio and highly express Oct-4 in the nucleus and SSEA-4 and CD133 antigens on the surface. Finally, we found 2 to 3 times higher numbers of VSELs in CB samples from vaginal deliveries as compared to scheduled C-sections. This supports the idea that VSEL are released into CB due to delivery-related stress/hypoxia. In conclusion, CB contains a population of VSELs but ~50% of these cells are not recovered by currently employed volume-reduction strategies because of their unique morphology. Taking into consideration that VSELs may be employed in regenerative medicine, novel volume reduction/erythrocyte depletion strategies require development in CB banking to avoid loss of these rare, primitive, and important cells. Figure Figure

scholarly journals Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism

2013 ◽  
Vol 11 (1) ◽  
pp. 196 ◽  
Author(s):  
Yong-Tao Lv ◽  
Yun Zhang ◽  
Min Liu ◽  
Jia-na-ti Qiuwaxi ◽  
Paul Ashwood ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Mononuclear Cells ◽  
Human Cord Blood ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

CD45−/ALDHlow/SSEA-4+/Oct-4+/CD133+/CXCR4+/Lin− Very Small Embryonic-Like (VSEL) Stem Cells Isolated from Umbilical Cord Blood as Potential Long Term Repopulating Hematopoietic Stem Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2444-2444
Author(s):  
Ewa K Zuba-Surma ◽  
Magdalena Kucia ◽  
Rui Liu ◽  
Mariusz Z Ratajczak ◽  
Janina Ratajczak
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Mononuclear Cells ◽  
Hematopoietic Stem ◽  
Hematopoietic Activity

Abstract Recently, we identified a population of very small embryonic-like (VSEL) stem cells in umbilical cord blood (CB) (Leukemia2007;21:297–303) These VSELs are: smaller than erythrocytes; SSEA-4+/Oct-4+/CD133+/CXCR4+/Lin−/CD45−; responsive to SDF-1 gradient; and iv) possessing large nuclei that contain unorganized chromatin (euchromatin). Data obtained in a murine model indicate that a similar cell population isolated from bone marrow (BM) does not reveal hematopoietic activity after isolation. However, in appropriate models (i.e., in vitro co-culture over OP-9 cells or in vivo after intra bone injection), these cells contribute to hematopoiesis and thus possesses potential of long term repopulating hematopoietic stem cells (LT-HSCs). To investigate the hematopoietic activity of CB-derived, CD45 negative VSELs, we employed staining with Aldefluor detecting aldehyde dehydrogenase (ALDH), the enzyme expressed in primitive hematopoietic cells. We sorted CD133+/CD45−/ALDHhigh and CD133+/CD45−/ALDHlow sub-fractions of VSELs from CB samples and established that both freshly sorted CB-derived populations did not grow hematopoietic colonies in vitro. However, when activated/expanded over OP-9 stroma cells, they exhibit hematopoietic potential and initiate hematopoietic colonies composed of CD45+ cells when replated into methylcellulose cultures. Furthermore, while CD133+/CD45−/ALDHhigh VSELs gave raise to hematopoietic colonies after the first replating, the formation of colonies by CD133+/CD45−/ALDHlow VSELs was delayed. The data indicate that both populations of CD45− cells may acquire hematopoietic potential; however hematopoietic specification is delayed for CD133+/CD45−/ALDHlow cells (Fig. 1A). In parallel, real time PCR analysis revealed that freshly isolated CD133+/CD45−/ALDHhigh VSELs express more hematopoietic transcripts (e.g., c-myb, 80.2±27.4 fold difference) while CD133+/CD45−/ALDHlow exhibit higher levels of pluripotent stem cell markers (e.g., Oct-4, 119.5±15.5 fold difference) as compared to total CB mononuclear cells (Fig. B). Furthermore and somewhat unexpectedly, we found that because of their unusually small size, these important cells may be partially depleted (in 42.5±12.6%) during standard preparation strategies of CB units for storage that employ volume reduction. In conclusion, our data suggest very small CB mononuclear cells expressing VSEL markers that are CD133+/CD45−/ALDHlow are highly enriched for the most primitive population of LT-HSCs. These cells may be responsible for long term CB engraftment and be a population of cells from which HSCs should be expanded. We are currently testing this in an in vivo model by performing heterotransplants of CD45− ALDHlow VSELs into immunodeficient mice. It is important to stress that currently employed, routine CB processing strategies may lead up to ~50% loss of these small cells that are endowed with such remarkable hematopoietic activity. Figure Figure

The Feature of SALL4 and BMI-1 Expression in Placenta and Umbilical Cord Blood

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4800-4800
Author(s):  
Shaohua Chen ◽  
Qi Shen ◽  
Lijian Yang ◽  
Bo Li ◽  
Yupo Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Research Funding ◽  
Mononuclear Cells ◽  
Expression Level ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem ◽  
Expression Levels

Abstract Abstract 4800 The SALL4 is a newly discovered pluripotency stem cell factor involved in the self-renewing, hematopoietic stem cells (HSCs) and leukemic stem cells. Its important role in normal HSCs and leukemic stem cells is supported by its interactions with several key players, like BMI-1, a putative oncogene of the Polycomb group family, controlling specific target genes involved in development, cell differentiation, proliferation, and senescence. Little is known the expression feature of SALL4 and BMI-1 mRNA in placenta and umbilical cord blood (UCB). In this study, the mRNA expression level of SALL4 and BMI-1 in 10 cases placenta tissues and the mononuclear cells from the corresponding UCB (CBMCs) were measured by real-time PCR with SYBR Green I technique, β2-microglobulin gene (β2M) was used as an endogenous reference, mononuclear cells from 10 healthy adults peripheral blood (PBMCs) and 2 cases of adult thymic cells served as control. The result showed that the expression level of both SALL4 and BMI-1 in placenta (Median: 34.36 and 17.55 respectively) were significantly higher than those from CBMCs (Median: 11.3 and 2.07 respectively) (p=0.007, p=0.001) and PBMCs (Median: 0.64 and 0.03 respectively) (P<0.001, P<0.001). Moreover, both SALL4 and BMI-1 expression levels in CBMCs were significant higher than those from PBMCs (P=0.002, P=0.001). And the expression of SALL4 could be detected in thymic cells. Correlation analysis was performed among the relative expression levels of SALL4 and BMI-1. The results showed that significant positive correlation between the expression levels of SALL4 and BMI-1 was observed in placenta tissues and CBMCs, as well as in PBMCs (rs=0.648, P=0.043, rs=0.721, P=0.019, rs=-0.697, P=0.025). In conclusions, the expression level of SALL4 and BMI-1 might be related to the numbers of hematopoietic stem cells, placenta tissues may be as an appropriate model for investigating gene regulation of SALL4 and BMI-1, while the significance of expression both genes in PBMCs and thymic cells is needed further investigation. Disclosures: Chen: National Natural Science Foundation of China(no. 30871091): Research Funding; the Fundamental Research Funds for the Central Universities (No. 21610603): Research Funding.

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 &lt; 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.

Potential Role of Immunosuppression in Therapeutic Effects Conferred by Cord Blood- Derived Mesenchymal Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2302-2302
Author(s):  
Nagwa S. El-Badri (Dajani) ◽  
Denis English ◽  
Amal Hakki ◽  
Sriram Mudhusoodanan ◽  
Cyndy D. Sanberg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Cord Blood ◽  
Immune Modulation ◽  
Mononuclear Cells ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Peripheral Blood Mononuclear ◽  
Murine Splenocytes

Abstract Our previous studies consistently demonstrate enhanced neural protective effects of cord blood in comparison to stem cells from adult marrow. Similarly, cord blood possesses diminished immuno-stimulatory activity, and the basis of this effect has not been defined. Since neural damage may be potentiated by immune activation of inflammatory cascades, we examined the effects of cord blood-derived MSCs (mesenchymal stem cells) on immune responses. We isolated and characterized a population of cord blood MSCs. These cells maintained their pluripotency in culture. Progeny generated in the absence of differentiation were strongly adherent, did not express CD34, CD45, CD3, CD19 antigens, and did not generate hematopoietic colonies in methylcellulose. However, cultured cord blood MSCs possessed a remarkable ability to support the proliferation as well as the differentiation of hematopoietic cells in vitro. In addition, supernatants from cultured cord blood MSCs promoted survival of peripheral blood mononuclear cells cultured under conditions designed to induce cell stress and limit protein synthesis. We examined immune modulation by cord blood MSCs after co-culture with murine splenocytes. While spleen cells from normal C57Bl/6 mice exhibited a prominent IgM response after immunization with the T-cell dependent antigen, SRBCs, this response was significantly decreased after incubation with cord blood MSCs. Consistently, cord blood MSCs mitigated the enhanced mixed lymphocyte proliferative response C57Bl/6 T-cells exhibit when exposed to lymphocytes from non-related animals. To investigate whether these immune suppressive properties could be therapeutically useful in a transplantation model for autoimmune disease, cord blood MSCs were transplanted into sublethally irradiated BXSB mouse model for systemic lupus. Thirty days after infusion, defective IgM humoral immune responses of splenocytes of these mice normalized. This normalization paralleled normalization of the disrupted lymphoid cellularity observed in the spleens of diseased animals. Our results are consistent with the hypothesis that immune regulation is involved in the therapeutic utility of MSCs.

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