scholarly journals Umbilical cord blood plasma-derived exosomes as a novel therapy to reverse liver fibrosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yu-Jen Huang ◽  
Jerry Cao ◽  
Chih-Yuan Lee ◽  
Yao-Ming Wu
Keyword(s):  
Liver Fibrosis ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Transforming Growth Factor ◽  
Stellate Cell ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Therapeutic Effects

Abstract Background Cirrhosis is a chronic liver disease whereby scar tissue replaces healthy liver parenchyma, leading to disruption of the liver architecture and hepatic dysfunction. Currently, there is no effective disease-modifying therapy for liver fibrosis. Recently, our group demonstrated that human umbilical cord blood (UCB) plasma possesses therapeutic effects in a rat model of acute liver failure. Methods In the current study, we tested whether exosomes (Exo) existed in UCB plasma and if they produced any antifibrotic benefits in a liver fibrosis model. Results Our results showed that UCB-Exo improved liver function and increased matrix metalloproteinase/tissue inhibitor of metalloproteinase degradation to reduce the degree of fibrosis. Moreover, UCB-Exo were found to suppress hepatic stellate cell (HSC) activity in vitro. These effects were associated with suppression of transforming growth factor-β/inhibitor of DNA binding 1 signaling. Conclusions These results further support that UCB-Exo have antifibrotic effects in mice with liver fibrosis and activated HSCs and may herald a new cell-free antifibrotic therapy.

Evaluations of Intravenous Administration of CD34+ Human Umbilical Cord Blood Cells in a Mouse Model of Neonatal Hypoxic-Ischemic Encephalopathy

2016 ◽  
Vol 38 (5) ◽  
pp. 331-341 ◽  
Author(s):  
Makiko Ohshima ◽  
Akihiko Taguchi ◽  
Yoshiaki Sato ◽  
Yuko Ogawa ◽  
Satoshi Saito ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Intravenous Administration ◽  
Umbilical Cord Blood ◽  
Treatment Protocol ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Neonatal Encephalopathy ◽  
Ischemic Encephalopathy

Several cell therapies have been explored as novel therapeutic strategies for neonatal encephalopathy because the benefits of current treatments are limited. We previously reported that intravenous administration of human umbilical cord blood (hUCB) CD34+ cells (hematopoietic stem cells/endothelial progenitor cells) at 48 h after insult exerts therapeutic effects in neonatal mice with stroke, i.e., permanent middle cerebral artery occlusion. Although neonatal stroke and hypoxic-ischemic encephalopathy (HIE) are grouped under the term “neonatal encephalopathy,” their pathogenesis differs. However, little is known about the differences in the effects of the same treatment between these 2 diseases. In this study, we investigated whether the same treatment protocol exerts therapeutic effects in neonatal mice with HIE. The treatment significantly ameliorated the decreased cerebral blood flow in the ischemic penumbra. Although the cylinder and rotarod tests showed a trend of amelioration of behavioral impairments from the treatment, these were not statistically significant. Morphological brain injuries were not altered by treatment. The cell administration did not cause any adverse effects apart from hyperactivity in the open-field test. Some of these findings are consistent with the results obtained in our previous study using a stroke model, but others are not. This study suggests that the treatment protocol needs to be optimized for each pathological condition.

scholarly journals Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2847-2857 ◽  
Author(s):  
Keli L. Hippen ◽  
Paul Harker-Murray ◽  
Stephen B. Porter ◽  
Sarah C. Merkel ◽  
Aryel Londer ◽  
...  
Keyword(s):  
T Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Transforming Growth Factor ◽  
Antigen Presenting Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Artificial Antigen ◽  
Antigen Presenting

Abstract Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)–coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor β (TGF-β) secretion and the potency of Treg suppressor function. aAPCs modified to coexpress OX40L or 4-1BBL expanded UCB Tregs to a significantly greater extent than bead- or nonmodified aAPC cultures, reaching mean expansion levels exceeding 1250-fold. Despite the high expansion and in contrast to studies using other Treg sources, neither OX40 nor 4-1BB signaling of UCB Tregs reduced in vitro suppression. UCB Tregs expanded with 4-1BBL expressing aAPCs had decreased levels of proapoptotic bim. UCB Tregs expanded with nonmodified or modified aAPCs versus beads resulted in higher survival associated with increased Treg persistence in a xeno-geneic graft-versus-host disease lethality model. These data offer a novel approach for UCB Treg expansion using aAPCs, including those coexpressing OX40L or 4-1BBL.

The use of hemopoietic stem cells derived from human umbilical cord blood to promote restoration of spinal cord tissue and recovery of hindlimb function in adult rats

2006 ◽  
Vol 5 (5) ◽  
pp. 424-433 ◽  
Author(s):  
Yutaka Nishio ◽  
Masao Koda ◽  
Takahito Kamada ◽  
Yukio Someya ◽  
Katsunori Yoshinaga ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Functional Recovery ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Hemopoietic Stem Cells

Object The use of human umbilical cord blood (HUCB) cells has been reported to improve functional recovery in cases of central nervous system injuries such as stroke, traumatic brain injury, and spinal cord injury (SCI). The authors investigated the effects of hemopoietic stem cells that were derived from HUCB and transplanted into the injured spinal cords of rats. Methods One week after injury, an HUCB fraction enriched in CD34-positive cells was transplanted into the experimental group. In control animals, vehicle (Matrigel) was transplanted. Recovery of motor functions was assessed using the Basso, Beattie, and Bresnahan Locomotor Scale, and immunohistochemical examinations were performed. Cells from HUCB that were CD34 positive improved functional recovery, reduced the area of the cystic cavity at the site of injury, increased the volume of residual white matter, and promoted the regeneration or sparing of axons in the injured spinal cord. Immunohistochemical examination revealed that transplanted CD34-positive cells survived in the host spinal cord for at least 3 weeks after transplantation but had disappeared by 5 weeks. The transplanted cells were not positive for neural markers, but they were positive for hemopoietic markers. There was no evidence of an immune reaction at the site of injury in either group. Conclusions These results suggest that transplantation of a CD34-positive fraction from HUCB may have therapeutic effects for SCI. The results of this study provide important preclinical data regarding HUCB stem cell–based therapy for SCI.

Therapeutic Potential of Endothelial Colony Forming Cells Derived from Human Umbilical Cord Blood

2019 ◽  
Vol 14 (6) ◽  
pp. 460-465 ◽  
Author(s):  
Jing Jia ◽  
Baitao Ma ◽  
Shaoshuai Wang ◽  
Ling Feng
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Tissue Regeneration ◽  
Umbilical Cord Blood ◽  
Therapeutic Potential ◽  
Human Umbilical Cord Blood ◽  
Proliferative Potential ◽  
Human Umbilical Cord ◽  
Preclinical Studies ◽  
Endothelial Colony Forming Cells

Endothelial progenitor cells (EPCs) are implicated in multiple biologic processes such as vascular homeostasis, neovascularization and tissue regeneration, and tumor angiogenesis. A subtype of EPCs is referred to as endothelial colony-forming cells (ECFCs), which display robust clonal proliferative potential and can form durable and functional blood vessels in animal models. In this review, we provide a brief overview of EPCs’ characteristics, classification and origins, a summary of the progress in preclinical studies with regard to the therapeutic potential of human umbilical cord blood derived ECFCs (CB-ECFCs) for ischemia repair, tissue engineering and tumor, and highlight the necessity to select high proliferative CB-ECFCs and to optimize their recovery and expansion conditions.

Hoechst dye efflux reveals a novel CD7+CD34− lymphoid progenitor in human umbilical cord blood

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2125-2133 ◽  
Author(s):  
Robert W. Storms ◽  
Margaret A. Goodell ◽  
Alan Fisher ◽  
Richard C. Mulligan ◽  
Clay Smith
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Large Population ◽  
Lymphoid Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract A novel Hoechst 33342 dye efflux assay was recently developed that identifies a population of hematopoietic cells termed side population (SP) cells. In the bone marrow of multiple species, including mice and primates, the SP is composed primarily of CD34−cells, yet has many of the functional properties of hematopoietic stem cells (HSCs). This report characterizes SP cells from human umbilical cord blood (UCB). The SP in unfractionated UCB was enriched for CD34+ cells but also contained a large population of CD34− cells, many of which were mature lymphocytes. SP cells isolated from UCB that had been depleted of lineage-committed cells (Lin− UCB) contained CD34+ and CD34− cells in approximately equivalent proportions. Similar to previous descriptions of human HSCs, the CD34+Lin− SP cells were CD38dimHLA-DRdimThy-1dimCD45RA−CD71−and were enriched for myelo-erythroid precursors. In contrast, the CD34−Lin− SP cells were CD38−HLA-DR−Thy-1−CD71−and failed to generate myelo-erythroid progeny in vitro. The majority of these cells were CD7+CD11b+CD45RA+, as might be expected of early lymphoid cells, but did not express other lymphoid markers. The CD7+CD34−Lin− UCB SP cells did not proliferate in simple suspension cultures but did differentiate into natural killer cells when cultured on stroma with various cytokines. In conclusion, the human Lin− UCB SP contains both CD34+ multipotential stem cells and a novel CD7+CD34−Lin− lymphoid progenitor. This observation adds to the growing body of evidence that CD34− progenitors exist in humans.

scholarly journals Endothelial cell precursors are normal components of human umbilical cord blood

1997 ◽  
Vol 98 (3) ◽  
pp. 775-777 ◽  
Author(s):  
Mie Nieda ◽  
Andrew Nicol ◽  
Patricia Denning‐Kendall ◽  
John Sweetenham ◽  
Ben Bradley ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord
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