Assessment of the angiogenic potential of human umbilical cord-derived perivascular cells and bone marrow MSCs using novel functional in vitro assays

Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting thatin vitropredifferentiation could be a potential strategy to increase their effectivenessin vivo.

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IN VITRO HEPATIC DIFFERENTIATION OF HUMAN UMBILICAL CORD BLOOD AND BONE MARROW CELLS

Pediatric Hematology and Oncology ◽

10.1080/08880010802234614 ◽

2008 ◽

Vol 25 (6) ◽

pp. 481-491 ◽

Cited By ~ 7

Author(s):

Yun-Jae Jung ◽

Kyung-Ha Ryu ◽

Kyung-A Cho ◽

So-Youn Woo ◽

Ju-Young Seoh ◽

...

Keyword(s):

Bone Marrow ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Bone Marrow Cells ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord ◽

Hepatic Differentiation ◽

Marrow Cells

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Human umbilical cord perivascular cells (HUC-PVCs) protect axons from degeneration in an in vitro peripheral nervous system injury model

Cytotherapy ◽

10.1016/j.jcyt.2015.03.501 ◽

2015 ◽

Vol 17 (6) ◽

pp. S56

Author(s):

Tanya Barretto ◽

Katya Park ◽

Leila Maghen ◽

Shlomit Kenigsberg ◽

Andree Gauthier-Fisher ◽

...

Keyword(s):

Nervous System ◽

Peripheral Nervous System ◽

Umbilical Cord ◽

Human Umbilical Cord ◽

Perivascular Cells ◽

Injury Model

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Human multipotential progenitor cells (CFU-GEMM) have extensive replating capacity for secondary CFU-GEMM: an effect enhanced by cord blood plasma

Blood ◽

10.1182/blood.v81.4.942.bloodjournal814942 ◽

1993 ◽

Vol 81 (4) ◽

pp. 942-949 ◽

Cited By ~ 1

Author(s):

CE Carow ◽

G Hangoc ◽

HE Broxmeyer

Keyword(s):

Bone Marrow ◽

Cord Blood ◽

Umbilical Cord ◽

Interleukin 1 ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord ◽

Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

The replating capability of human umbilical cord blood (CB) multipotential (CFU-GEMM) progenitors was assessed in vitro as an estimate of self-renewal using erythropoietin (Epo), steel factor (SLF), and either fetal bovine serum (FBS) or CB plasma. This study found a much higher replating efficiency for CB CFU-GEMM than previously reported, in terms of the percentage of colonies that could be replated, the number of secondary colonies per replated primary colony, and the size of secondary colonies. Moreover, the majority of secondary colonies were CFU-GEMM-derived. Although the percentages of bone marrow CFU-GEMM that replate was similar to that for CB CFU-GEMM and the sizes of secondary bone marrow and CB CFU-GEMM were also similar, replated CB CFU-GEMM gave rise to far greater numbers of secondary colonies. No tertiary colonies were observed when secondary CFU-GEMM were replated. Detection of extensive secondary replating potential was enhanced by the addition of CB plasma to the cultures. This activity was not found in either adult blood (PB) plasma, umbilical cord vein endothelial cell-conditioned medium (ECCM), FBS plus ECCM, or FBS plus the combination of interleukin-1 (IL-1), IL-3, IL-6, IL-11, granulocyte colony-stimulating factor, and granulocyte- macrophage colony-stimulating factor. Whether the CB plasma-enhancing activity for CFU-GEMM replating capacity is attributable to a novel factor or factors, or represents effects of other known cytokines, alone or in combination, remains to be determined. Of particular relevance, these studies suggest that human CFU-GEMM have some degree of stemness and perhaps should be classified as a subset of stem cells.

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Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair

10.21203/rs.2.23883/v2 ◽

2020 ◽

Author(s):

Ning Zhang ◽

JinYun Zhu ◽

QunChao Ma ◽

Yun Zhao ◽

YingChao Wang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Umbilical Cord ◽

Cardiac Repair ◽

Human Umbilical Cord ◽

Bone Marrow Mscs ◽

Myocardial Repair ◽

Related Factors

Abstract Background: Age and other cardiovascular risk factors have been reported to impair the activities of mesenchymal stem cells (MSCs), which will affect the efficacy of stem cell transplantation. The objective of the study is to investigate whether exosomes derived from human umbilical cord MSCs (UMSCs) could enhance the activities of bone marrow MSCs from old person (OMSCs), and improve their capacity for cardiac repair. Methods: Exosomes extracted from conditioned medium of UMSCs were used to treat OMSCs to generate OMSCsExo. The key molecule in the exosomes that have potential to rejuvenate aged MSCs were screened, and the role of OMSC was tested in the mouse model of mycardiac infarction(MI). Results: We found the activity of senescence-associated β-galactosidase and the expression of aging-related factors such as p53, p21, and p16 were significantly higher in OMSCs than those in UMSCs. After treatment with UMSC exosomes, these senescence phenotypes of OMSCs were remarkably reduced. The proliferation, migration, differentiation, anti-apoptotic and paracrine effect were increased in OMSCsExo. In vivo study, mice with cardiac infarction had significantly better cardiac function, less fibrosis, and more angiogenesis after they were injected with OMSCsExo as compared with those with OMSC. There was more miR-136 expression in UMSCs and OMSCsExo than in OMSCs. Upregulation of miR-136 by transfection of miR-136 mimic into OMSCs significantly attenuated the apoptosis and senescence of OMSCs. Apoptotic peptidase activating factor (Apaf1) was found to be the downstream gene that is negatively regulated by miR-136 via directly targeting at its 3’UTR. Conclusion: Our data suggest that exosomes from young MSCs can improve activities of aged MSCs and enhance their function for myocardial repair by transferring exosomal miR-136 and downregulating Apaf1.

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Human multipotential progenitor cells (CFU-GEMM) have extensive replating capacity for secondary CFU-GEMM: an effect enhanced by cord blood plasma

Blood ◽

10.1182/blood.v81.4.942.942 ◽

1993 ◽

Vol 81 (4) ◽

pp. 942-949 ◽

Cited By ~ 74

Author(s):

CE Carow ◽

G Hangoc ◽

HE Broxmeyer

Keyword(s):

Bone Marrow ◽

Cord Blood ◽

Umbilical Cord ◽

Interleukin 1 ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord ◽

Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Abstract The replating capability of human umbilical cord blood (CB) multipotential (CFU-GEMM) progenitors was assessed in vitro as an estimate of self-renewal using erythropoietin (Epo), steel factor (SLF), and either fetal bovine serum (FBS) or CB plasma. This study found a much higher replating efficiency for CB CFU-GEMM than previously reported, in terms of the percentage of colonies that could be replated, the number of secondary colonies per replated primary colony, and the size of secondary colonies. Moreover, the majority of secondary colonies were CFU-GEMM-derived. Although the percentages of bone marrow CFU-GEMM that replate was similar to that for CB CFU-GEMM and the sizes of secondary bone marrow and CB CFU-GEMM were also similar, replated CB CFU-GEMM gave rise to far greater numbers of secondary colonies. No tertiary colonies were observed when secondary CFU-GEMM were replated. Detection of extensive secondary replating potential was enhanced by the addition of CB plasma to the cultures. This activity was not found in either adult blood (PB) plasma, umbilical cord vein endothelial cell-conditioned medium (ECCM), FBS plus ECCM, or FBS plus the combination of interleukin-1 (IL-1), IL-3, IL-6, IL-11, granulocyte colony-stimulating factor, and granulocyte- macrophage colony-stimulating factor. Whether the CB plasma-enhancing activity for CFU-GEMM replating capacity is attributable to a novel factor or factors, or represents effects of other known cytokines, alone or in combination, remains to be determined. Of particular relevance, these studies suggest that human CFU-GEMM have some degree of stemness and perhaps should be classified as a subset of stem cells.

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