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Home Archives for umbilical cord

Vitrification preserves Wharton’s Jelly up to a year

Posted on January 21, 2020 Written by nhriordan Leave a Comment

Wharton’s Jelly (WJ), one of the routinely discarded products of afterbirths, is a tissue rich in mesenchymal stem cells (MSC). Additionally, its extracellular matrix is rich in collagen, which makes it attractive as scaffolding for tissue engineering. For those of us working with WJ in the lab, a delicate balance must be struck between how to best preserve the tissue and ensuring that WJ is retaining its regenerative properties. In this article, the researchers used a process called vitrification to preserve WJ for up to a year and compared it to both fresh WJ tissue and conventionally cryopreserved WJ. They found that vitrified WJ retained properties comparable to fresh WJ: the extracellular matrix was still viable, and it was possible to isolate and expand MSC.

 


Gynecol Endocrinol. 2019 Jun 25:1-4. doi: 10.1080/09513590.2019.1632831.

Vitrified Wharton’s jelly tissue as a biomaterial for multiple tissue engineering applications.

Mallis P, Boulari D, Chachlaki P, Stavropoulos Giokas C, Michalopoulos E.

Abstract

Wharton’s Jelly (WJ) tissue is a promising biomaterial, for tissue engineering applications. However, its preservation over a long period in order to be readily available needs further optimization. A possible solution could be the vitrification and storage of WJ tissue at low temperatures. The aim of this study is to evaluate the effect of low temperature in the WJ tissue, which was stored at -196 °C, either with the vitrification or conventional cryopreservation methods. WJ tissues were isolated from human umbilical cords, cryopreserved with the above methods and remained for 1 year at -196 °C. Histological analysis of tissue’s extracellular matrix (ECM), isolation, and characterization of mesenchymal stromal cells (MSCs) were performed. Histological analysis revealed the presence of ECM components such as collagen, sulfated glycosaminoglycans (sGAGs), and the presence of cell nuclei only in vitrified samples. Furthermore, MSCs were isolated and expanded successfully from vitrified WJ tissues, whereas a few viable cells were obtained from conventionally cryopreserved tissues that were not further expanded. In conclusion, this study indicated the proper preservation of vitrified WJ tissues after 1 year of storage, which eventually could be used in tissue engineering and regenerative medicine approaches.


PMID: 31237154 DOI: 10.1080/09513590.2019.1632831

Filed Under: Uncategorized Tagged With: mesenchymal stem cells, umbilical cord

UCMSC secretions (exosomes) for Perinatal Brain Injury

Posted on October 3, 2019 Written by nhriordan Leave a Comment

As I’ve discussed in previous posts of this blog, the secretions of mesenchymal stem cells derived from umbilical cord (UCMSC) are of particular importance for their therapeutic properties, including neuroprotection (among others). This recent article examines the use of exosomes (extracellular vesicles secreted by UCMSC) in a rat model of perinatal brain injury. In humans, perinatal brain injury is a major complication of children born prematurely, causing injury to both gray and white matter, and having significant cognitive, motor and behavioral problems if the infants survive.

In this experiment, the researchers administered human UCMSC exosomes intranasally to the rats. The exosomes were able to reach the injured brain, where they reduced gray and white matter injuries, restored myelination and helped recover neuronal count, when compared to the control groups. Learning ability was improved in the rats who received UCMSC exosomes. The authors conclude that intranasal administration of UCMSC exosomes might be a promising strategy to prevent perinatal brain injury in human newborns.

 


Cells. 2019 Aug 8;8(8). pii: E855. doi: 10.3390/cells8080855.

Intranasally Administered Exosomes from Umbilical Cord Stem Cells Have Preventive Neuroprotective Effects and Contribute to Functional Recovery after Perinatal Brain Injury.

Thomi G, Joerger-Messerli M, Haesler V, Muri L, Surbek D, Schoeberlein A.

Abstract

Perinatal brain injury (PBI) in preterm birth is associated with substantial injury and dysmaturation of white and gray matter, and can lead to severe neurodevelopmental deficits. Mesenchymal stromal cells (MSC) have been suggested to have neuroprotective effects in perinatal brain injury, in part through the release of extracellular vesicles like exosomes. We aimed to evaluate the neuroprotective effects of intranasally administered MSC-derived exosomes and their potential to improve neurodevelopmental outcome after PBI. Exosomes were isolated from human Wharton’s jelly MSC supernatant using ultracentrifugation. Two days old Wistar rat pups were subjected to PBI by a combination of inflammation and hypoxia-ischemia. Exosomes were intranasally administered after the induction of inflammation and prior to ischemia, which was followed by hypoxia. Infrared-labeled exosomes were intranasally administered to track their distribution with a LI-COR scanner. Acute oligodendrocyte- and neuron-specific cell death was analyzed 24 h after injury in animals with or without MSC exosome application using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical counterstaining. Myelination, mature oligodendroglial and neuronal cell counts were assessed on postnatal day 11 using immunohistochemistry, Western blot or RT-PCR. Morris water maze assay was used to evaluate the effect of MSC exosomes on long-term neurodevelopmental outcome 4 weeks after injury. We found that intranasally administered exosomes reached the frontal part of the brain within 30 min after administration and distributed throughout the whole brain after 3 h. While PBI was not associated with oligodendrocyte-specific cell death, it induced significant neuron-specific cell death which was substantially reduced upon MSC exosome application prior to ischemia. MSC exosomes rescued normal myelination, mature oligodendroglial and neuronal cell counts which were impaired after PBI. Finally, the application of MSC exosomes significantly improved learning ability in animals with PBI. In conclusion, MSC exosomes represent a novel prevention strategy with substantial clinical potential as they can be administered intranasally, prevent gray and white matter alterations and improve long-term neurodevelopmental outcome after PBI.


PMID: 31398924 DOI: 10.3390/cells8080855

Filed Under: Uncategorized Tagged With: mesenchymal stem cells, umbilical cord

Immunomodulation of UCMSC in Rheumatoid Arthritis

Posted on September 26, 2019 Written by nhriordan Leave a Comment

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints: the immune system mistakenly attacks the lining of the joints, causing pain, stiffness and inflammation.

In this pre-clinical study, researchers used a model of RA in rats and injected them with mesenchymal stem cells derived from human umbilical cord (UC-MSC). After assessing the state of their joints following treatment, the animals were dissected to study their levels of inflammatory cytokines, lymphocytes, and other relevant markers, compared to the control group who didn’t receive UC-MSC, and another group who was treated with methotrexate (MTX). The joints of rats treated with UC-MSC did better than those in the other two groups. This, coupled with the fact that UC-MSC were found to regulate inflammatory cytokines as well as MTX in rats, leads the researchers to conclude that UC-MSC may have a broader application prospect than MTX for RA treatment.

Additionally, they extracted blood from 6 RA patients and cultured them in the lab alongside UC-MSC. After observing their interactions, they concluded that that UC-MSC play an immunoregulatory role by balancing Treg/Th17 and inflammatory factors in RA patients.

Treating RA in humans with UC-MSC safely and efficiently is well supported by studies such as this one – we’ll undoubtedly be seeing more articles on this subject in the next months.


Int Immunopharmacol. 2019 Sep;74:105687. doi: 10.1016/j.intimp.2019.105687. Epub 2019 Jul 8.

Immunomodulatory effect of human umbilical cord mesenchymal stem cells on T lymphocytes in rheumatoid arthritis.

Ma D, Xu K, Zhang G, Liu Y, Gao J, Tian M, Wei C, Li J, Zhang L.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease which is lack of effective therapies. Abnormal activation, proliferation, and differentiation of T lymphocytes are closely related to RA. Mesenchymal stem cells (MSCs) can be used for RA treatment due to their immunoregulatory effects. However, the specific molecular mechanisms have not been fully elucidated and the therapeutic effect has been inconsistent. This study investigated the immunomodulatory effect of human umbilical cord MSCs (hUCMSCs) on T lymphocytes in collagen-induced arthritis (CIA) rats and RA patients to clarify the possible mechanism of hUCMSCs in RA treatment. The effects of hUCMSCs on arthritis index, radiological and synovial pathological changes, T lymphocyte proliferation and apoptosis, RORγt and Foxp3 expression, Th17 and Treg cell ratios, and IL-17 and TGF-β levels were assessed in CIA rats. Further, we verified the effect of hUCMSCs in RA patients, and compared the effect of hUCMSCs with that of hUCMSC derived extracellular vesicles (EVs). The results showed that hUCMSCs inhibited the proliferation and promoted apoptosis in T lymphocytes, downregulated RORγt mRNA and protein expression, decreased Th17 cell ratio, upregulated Foxp3 mRNA and protein expression, and increased Treg cell ratio in the spleen. Furthermore, they downregulated RORγt and Foxp3 expression in the joints, and inhibited IL-17 and promoted TGF-β expression in the serum, thereby improving arthritis, delaying radiological progression, and inhibiting synovial hyperplasia in CIA rats. In vitro the effects of hUCMSCs and EVs were consistent with those in vivo. Therefore, hUCMSCs may be expected to serve as a new therapy for RA.


PMID: 31295689 DOI: 10.1016/j.intimp.2019.105687

Filed Under: Uncategorized Tagged With: mesenchymal stem cells, rheumatoid arthritis, umbilical cord

It’s what they secrete

Posted on September 11, 2019 Written by nhriordan Leave a Comment

In my recent talks, I’ve often highlighted that the secretions of MSCs are what is behind their therapeutic effect – this is supported by the findings of several publications investigating their paracrine properties. This 2019 paper extensively reviews the recent research about the role of secreted extracellular vesicles of UC-MSC. The authors go over 35 studies that used extracellular vesicles from UC-MSC to treat diverse conditions in animal models and in vitro (in the lab), with very positive outcomes.


J Cell Physiol. 2019 Jun 28. doi: 10.1002/jcp.29004.

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm.

Abbaszadeh H, Ghorbani F, Derakhshani M, Movassaghpour A, Yousefi M.

Abstract

Mesenchymal stem cells (MSCs) have been revealed to hold great potential for the development of new treatment approaches for various diseases. However, the clinical use of these cells is limited due to their tumorigenic effects. The therapeutic benefits of MSCs are largely dependent on paracrine factors including extracellular vesicles (EVs). EVs are nano-sized bilayer membrane structures containing lipids, microRNAs and proteins which play key roles in cell-to-cell communications. Because of their lower immunogenicity, tumorigenicity, and easier management, EVs have emerged as a new promising alternative to whole-cell therapy. Therefore, this paper reviews current preclinical studies on the use of EVs derived from human umbilical cord MSCs (hucMSCs) as a therapeutic approach in treatment of several diseases including neurological, cardiovascular, liver, kidney, and bone diseases as well as the cutaneous wound, inflammatory bowel disease, cancers, infertility, and other disorders.


PMID: 31254289 DOI: 10.1002/jcp.29004

Filed Under: Uncategorized Tagged With: mesenchymal stem cells, umbilical cord

Umbilical Cord Mesenchymal Stem Cells as Preeclampsia Treatment

Posted on March 29, 2016 Written by nhriordan 3 Comments

Treatment with human umbilical cord mesenchymal stem cells is shown to be effective in controlling hypertension and reducing the infiltration of inflammatory cells in the placenta, in this preeclampsia rat model.


Reprod Sci. 2016 Feb 17. pii: 1933719116630417.

Effect of Human Umbilical Cord Mesenchymal Stem Cell Transplantation in a Rat Model of Preeclampsia.

Wang LL, Yu Y, Guan HB, Qiao C.

Abstract

OBJECTIVE: To test the effects of human umbilical cord mesenchymal stem cell (HU-MSC) transplantation on reversing preeclampsia (PE) symptoms in a lipopolysaccharide (LPS)-induced rat PE model.

METHODS: Human umbilical cord MSCs were detected, isolated, and cultured. Human umbilical cord MSC transplantation was conducted. Expressions of inflammatory cytokines in serum and placental tissue were measured by enzyme-linked immunosorbent assay. Changes in inflammatory cytokines, peroxisome proliferator-activated receptor γ (PPARγ), laminin receptor 1 (LR1), matrix metalloproteinase (MMP) 2, and MMP-9 messenger RNA (mRNA) levels in placental tissue were recorded by quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blotting were performed for PPARγ detection.

RESULTS: The LPS group exhibited increased blood pressure and proteinuria and decreased fetal weight compared to the normal pregnancy (NP) group (all P < .05). The LPS + MSC group presented lowered blood pressure and higher fetal weight than the LPS group (P < .05). The levels of interferon γ, tumor necrosis factor α (TNF-α), interleukin (IL) 1β, IL-6, IL-8, IL-12, and intercellular adhesion molecule 1 (ICAM-1) increased and the levels of IL-4 and IL-10 levels decreased in the LPS group compared to the NP group (all P < .05). Tumor necrosis factor α, IL-6, IL-12, and ICAM-1 levels decreased and IL-10 level increased in the LPS + MSC group compared to the LPS group (all P < .05). The LPS-MSC group showed lower mRNA expressions of TNF-α, IL-6, MMP-2, MMP-9, and ICAM-1 and higher mRNA expressions of IL-10, PPARγ, and LR1 than the LPS group (all P < .05).

CONCLUSION: In summary, HU-MSC transplantation may be extremely beneficial for PE therapy.

© The Author(s) 2016.


PMID: 26887428

 

Filed Under: Uncategorized Tagged With: mesenchymal stem cells, preeclampsia, stem cells, umbilical cord

Umbilical cord MSC treatment improves liver condition in rat acute liver failure

Posted on March 23, 2016 Written by nhriordan Leave a Comment

Human umbilical cord mesenchymal stem cells (hUCMSC) were found to improve liver condition in rats after acute liver failure, slowing the degeneration of liver cells. The results were comparable whether treatment was administered intravenously or via intrahepatic injection.


Int J Clin Exp Pathol. 2015 Dec 1; 8(12):15854-62.

Transplantation of umbilical cord mesenchymal stem cells via different routes in rats with acute liver failure.

Zheng S, Yang J, Yang J, Tang Y, Shao Q, Guo L, Liu Q.

Abstract

OBJECTIVE: This study aimed to compare the therapeutic efficacy of transplantation of human umbilical cord mesenchymal stem cells (hUCMSC) in different routes in acute hepatic failure (ALF) in rats.

METHODS: hUCMSCs were isolated and identified by detection of surface antigens via flow cytometry. In T group and H group, ALF rats received hUCMSC transplantation through the tail vein and intrahepatic injection, respectively. In hUCMSC group, healthy rats received hUCMSCs transplantation via the tail vein. In ALF group, rats received injection of normal saline through the tail vein.

RESULTS: The TBil and ALT in ALF rats with and without transplantation were significantly higher than in healthy rats (P<0.05). HE staining of the liver showed obvious hepatocyte regeneration and reduced infiltration of inflammatory cells, and liver pathology was improved in T group and H group as compared to ALF group. At 3 d after transplantation, CK18 expression was detectable in both H group and T group. At 1 w and 2 w, the mRNA expressions of CK8, CK18 and AFP in H group and T group were significantly different from those in ALF group (P<0.05). The liver function and differentiation of stem cells were comparable between H group and T group (P>0.05).

CONCLUSION: hUCMSCs transplantation can improve the liver function and promote the liver repair following ALF. hUCMSCs transplantation via tail vein has similar therapeutic efficacy to that through intrahepatic injection.


PMID: 26884856

PMCID: PMC4730069

 

Filed Under: Uncategorized Tagged With: acute liver failure, liver, mesenchymal stem cells, stem cells, umbilical cord

Neil Riordan, PhD

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Recent Posts

  • Amnion-derived cells for regenerative medicine January 27, 2020
  • Vitrification preserves Wharton’s Jelly up to a year January 21, 2020
  • Adipose MSC for Spinal Cord Injury: ASIA Scores Improvement December 4, 2019
  • UCMSC secretions (exosomes) for Perinatal Brain Injury October 3, 2019
  • Immunomodulation of UCMSC in Rheumatoid Arthritis September 26, 2019

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