scholarly journals Comparison of the therapeutic effects of hUC-MSC intravenous delivery and intraperitoneal administration of MSCs encapsulated in alginate capsules for the treatment of rat liver cirrhosis

2021 ◽  
Author(s):  
Svitlana Rymar ◽  
Polina Pikus ◽  
Ianina Pokholenko ◽  
Polina Buchek ◽  
Nadiya Shuvalova ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Umbilical Cord ◽  
Therapeutic Potential ◽  
Intraperitoneal Administration ◽  
Liver Parenchyma ◽  
Negative Control ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Alginate Capsules ◽  
Therapeutic Properties

Mesenchymal stem cells are the most promising regenerative medicine tool for the treatment of various diseases, including liver disease, although the exact mechanism of their therapeutic action remains unclear. It was found that MSCs are captured by the lungs after systemic transplantation, quickly disappear, and are not detected at the site of injury, but at the same time exhibit an obvious therapeutic effect. Comparison of the MSC efficiency depending on the route of their administration may shed light on the mechanisms involved in the implementation of MSC therapeutic potential. In this work, we compared the therapeutic effects of human umbilical cord MSCs (hUC-MSCs) administered systemically and intraperitoneally in the form of MSCs encapsulated in alginate capsules in a CCl4-induced model of liver cirrhosis in rats. Our study showed that both treatments resulted in liver recovery. MSC transplantation by two different routes led to a decrease in collagen deposition, the disappearance of the fibrous area by the 13th week, and normalization of the morphometric parameters of liver parenchyma cells. The expression of some genes (EGF, alpha SMA, GFAP) which is activated in liver injury, decreased to the level observed in negative control animals. However, a detailed study of liver recovery in dynamics showed that encapsulated MSCs led to faster normalization in several parameters of the liver tissue. Our results showed that human umbilical cord MSCs effectively exhibit their therapeutic properties when using both methods of transplantation, however, intraperitoneal administration of encapsulated MSCs accelerated the process of liver regeneration.

scholarly journals Comparison of the Therapeutic Effects of hUC-MSC Intravenous Delivery and Intraperitoneal Administration of MSCs Encapsulated in Alginate Capsules for the Treatment of Rat Liver Cirrhosis

2021 ◽  
Vol 12 (4) ◽  
pp. 5054-5070
Keyword(s):  
Liver Cirrhosis ◽  
Umbilical Cord ◽  
Therapeutic Potential ◽  
Intraperitoneal Administration ◽  
Liver Parenchyma ◽  
Negative Control ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Alginate Capsules ◽  
Therapeutic Properties

Mesenchymal stem cells are the most promising regenerative medicine tool for treating various diseases, including liver disease, although the exact mechanism of their therapeutic action remains unclear. It was found that MSCs are captured by the lungs after systemic transplantation, quickly disappear, and are not detected at the site of injury but at the same time exhibit an obvious therapeutic effect. Comparison of the MSC efficiency depending on the route of their administration may shed light on the mechanisms involved in implementing MSC therapeutic potential. In this work, we compared the therapeutic effects of human umbilical cord MSCs (hUC-MSCs) administered systemically and intraperitoneally in the form of MSCs encapsulated in alginate capsules in a CCl4-induced model of liver cirrhosis in rats. Our study showed that both treatments resulted in liver recovery. MSC transplantation by two different routes led to a decrease in collagen deposition, the disappearance of the fibrous area by the 13th week, and the normalization of the morphometric parameters of liver parenchyma cells. In addition, the expression of some genes (EGF, alpha SMA, GFAP) which is activated in liver injury, decreased to the level observed in negative control animals. However, a detailed study of liver recovery in dynamics showed that encapsulated MSCs led to faster normalization in several parameters of the liver tissue. Our results showed that human umbilical cord MSCs effectively exhibit their therapeutic properties when using both transplantation methods. However, intraperitoneal administration of encapsulated MSCs accelerated the process of liver regeneration.

scholarly journals Hydrogen Peroxide Preconditioning Promotes Protective Effects of Umbilical Cord Vein Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis

2019 ◽  
Vol 10 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Tayebeh Mahmoudi ◽  
Kamal Abdolmohammadi ◽  
Hamed Bashiri ◽  
Mehdi Mohammadi ◽  
Mohammad Jafar Rezaie ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Umbilical Cord ◽  
Lung Tissue ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Umbilical Cord Vein ◽  
Tgf Β1

Purpose: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder with few available treatments. Mesenchymal stem cell therapy (MSCT), an innovative approach, has high therapeutic potential when used to treat IPF. According to recent data, preconditioning of MSCs can improve their therapeutic effects. Our research focuses on investigating the anti-inflammatory and antifibrotic effects of H2 O2 -preconditioned MSCs (p-MSCs) on mice with bleomycin-induced pulmonary fibrosis (PF). Methods: Eight-week-old male C57BL/6 mice were induced with PF by intratracheal (IT) instillation of bleomycin (4 U/kg). Human umbilical cord vein-derived MSCs (hUCV-MSCs) were isolated and exposed to a sub-lethal concentration (15 μM for 24 h) of H2 O2 in vitro. One week following the injection of bleomycin, 2×105 MSCs or p-MSCs were injected (IT) into the experimental PF. The survival rate and weight of mice were recorded, and 14 days after MSCs injection, all mice were sacrificed. Lung tissue was removed from these mice to examine the myeloperoxidase (MPO) activity, histopathological changes (hematoxylin-eosin and Masson’s trichrome) and expression of transforming growth factor beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) through immunohistochemistry (IHC) staining. Results: Compared to the PF+MSC group, p-MSCs transplantation results in significantly decreased connective tissue (P<0.05) and collagen deposition. Additionally, it is determined that lung tissue in the PF+pMSC group has increased alveolar space (P<0.05) and diminished expression of TGF-β1 and α-SMA. Conclusion: The results demonstrate that MSCT using p-MSCs decreases inflammatory and fibrotic factors in bleomycin-induced PF, while also able to increase the therapeutic potency of MSCT in IPF

scholarly journals Morphological features of recovery in model rats liver cirrhosis induced by CCl4 after transplantation of mesenchymal stem cells from human umbillical cord

2020 ◽  
Vol 26 ◽  
pp. 252-258
Author(s):  
P. O. Pikus ◽  
S. Yu. Rymar ◽  
N. S. Shuvalova ◽  
P. V. Butschek
Keyword(s):  
Extracellular Matrix ◽  
Liver Cirrhosis ◽  
Umbilical Cord ◽  
Rat Liver ◽  
Intraperitoneal Injection ◽  
Inhibitory Effect ◽  
Negative Control ◽  
Human Umbilical Cord ◽  
Experimental Liver

Aim. To study the process of recovery of rat liver in a model of cirrhosis, which was induced by intraperitoneal injection of CCl4, after transplantation human umbilical cord MSCs. Today in the world as an alternative to liver transplantation is offered cell therapy, which leads to the recovery of organ’s functions through the injection of MSCs. The key role of MSCs in the development of fibrosis and its final stage - liver cirrhosis is the inhibitory effect on the proliferation of the extracellular matrix. Methods. The methods of histology and morphometry were used in the work. Results. It was found, that 13 weeks after CCl4 induction, the amount of collagen increased 7 times, atrophic, sclerotic changes in the architectonics of rat liver and functional disorders of hepatocytes were observed. After transplantation of human umbilical cord MSCs - 6-7x106 cells / kg body weight of the animal, was shown that after 3 weeks the rate of collagen accumulation decreased and after 13 weeks the amount of ECMs and other morphometric indexes almost corresponded to the negative control. Conclusions. Studies have shown that transplantation MSCs from human umbilical cord leads to almost complete regeneration of the rat liver which was caused by experimental liver cirrhosis with intraperitoneal injection of CCl4. Keywords: human umbilical cord MSCs, extracellular matrix, hepatocytes.

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.

scholarly journals Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

2018 ◽  
Vol 27 (9) ◽  
pp. 1352-1367 ◽  
Author(s):  
Fu Yuan Yang ◽  
Rui Chen ◽  
Xiaohu Zhang ◽  
Biao Huang ◽  
Lai Ling Tsang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Therapeutic Effect ◽  
T Cell Activation ◽  
Activity Index ◽  
Intraperitoneal Administration ◽  
The Body ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

NGF Nanoparticles Enhance the Potency of Transplanted Human Umbilical Cord Mesenchymal Stem Cells for Myocardial Repair

2021 ◽  
Author(s):  
Wei Luo ◽  
Yanshan Gong ◽  
Fan Qiu ◽  
Yi Yuan ◽  
Wenwen Jia ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Therapeutic Potential ◽  
Contractile Function ◽  
Plga Nanoparticles ◽  
Mouse Heart ◽  
Human Umbilical Cord ◽  
Myocardial Repair ◽  
Cardiac Contractile Function ◽  
Group A ◽  
A Cell

In this study, we investigated whether human umbilical cord mesenchymal stem cell (hUCMSC) fibrin patches loaded with nerve growth factor (NGF) poly(lactic-co-glycolic acid) (PLGA) nanoparticles could enhance the therapeutic potency of hUCMSCs for myocardial infarction (MI). In vitro, NGF significantly improved the proliferation of hUCMSCs and mitigated cytotoxicity and apoptosis under hypoxic injury. NGF also promoted the paracrine effects of hUCMSCs on angiogenesis and cardiomyocyte protection. The tyrosine kinase A (TrkA) and phosphoinositide 3-kinase (PI3K)-serine/threonine protein kinase (Akt) signaling pathways in hUCMSCs were involved in the NGF-induced protection. NGF PLGA nanoparticles continued to release NGF for at least one month and also exerted a protective effect on hUCMSCs, the same with free NGF. In vivo, we treated MI mice with nothing (MI group), a cell-free fibrin patch with blank PLGA nanoparticles (MI+OP group), a cell-free fibrin patch with NGF nanoparticles (MI+NGF group), and hUCMSC fibrin patches with blank PLGA nanoparticles (MI+MSC group) or NGF PLGA nanoparticles (MSC+NGF group). Among these groups, the MSC+NGF group exhibited the best cardiac contractile function, the smallest infarct size, and the thickest ventricular wall. The application of NGF PLGA nanoparticles significantly improved the retention of transplanted hUCMSCs, and enhanced their ability to reduce myocardial apoptosis and promote angiogenesis in the mouse heart after MI. These findings demonstrate the promising therapeutic potential of hUCMSC fibrin cardiac patches loaded with NGF PLGA nanoparticles.

scholarly journals Therapeutic Potential of 47Sc in Comparison to 177Lu and 90Y: Preclinical Investigations

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 424 ◽  
Author(s):  
Klaudia Siwowska ◽  
Patrycja Guzik ◽  
Katharina A. Domnanich ◽  
Josep M. Monné Rodríguez ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Potential ◽  
Folate Receptor ◽  
Tumor Growth Inhibition ◽  
Therapeutic Effects ◽  
Targeted Radionuclide Therapy ◽  
Decay Properties ◽  
Therapeutic Properties ◽  
Folate Conjugate

Targeted radionuclide therapy with 177Lu- and 90Y-labeled radioconjugates is a clinically-established treatment modality for metastasized cancer. 47Sc is a therapeutic radionuclide that decays with a half-life of 3.35 days and emits medium-energy β−-particles. In this study, 47Sc was investigated, in combination with a DOTA-folate conjugate, and compared to the therapeutic properties of 177Lu-folate and 90Y-folate, respectively. In vitro, 47Sc-folate demonstrated effective reduction of folate receptor-positive ovarian tumor cell viability similar to 177Lu-folate, but 90Y-folate was more potent at equal activities due to the higher energy of emitted β−-particles. Comparable tumor growth inhibition was observed in mice that obtained the same estimated absorbed tumor dose (~21 Gy) when treated with 47Sc-folate (12.5 MBq), 177Lu-folate (10 MBq), and 90Y-folate (5 MBq), respectively. The treatment resulted in increased median survival of 39, 43, and 41 days, respectively, as compared to 26 days in untreated controls. There were no statistically significant differences among the therapeutic effects observed in treated groups. Histological assessment revealed no severe side effects two weeks after application of the radiofolates, even at double the activity used for therapy. Based on the decay properties and our results, 47Sc is likely to be comparable to 177Lu when employed for targeted radionuclide therapy. It may, therefore, have potential for clinical translation and be of particular interest in tandem with 44Sc or 43Sc as a diagnostic match, enabling the realization of radiotheragnostics in future.

scholarly journals Therapeutic Effect of Human Umbilical Cord Mesenchymal Stem Cells at Various Passages on Acute Liver Failure in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yongting Zhang ◽  
Yuwen Li ◽  
Wenting Li ◽  
Jie Cai ◽  
Ming Yue ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Umbilical Cord ◽  
Therapeutic Potential ◽  
Human Umbilical Cord ◽  
Sd Rats ◽  
Recipient Liver ◽  
Injured Liver

Recent studies have described beneficial effects of an infusion of mesenchymal stem cells (MSCs) derived from Wharton’s jelly tissue, for the treatment of acute liver failure (ALF). However, data on the therapeutic potential of culture-expanded MSCs are lacking. We examined the therapeutic potential of passage five (P5) and ten (P10) human umbilical cord- (hUC-) MSCs via their transplantation into Sprague-Dawley (SD) rats with D-galactosamine (D-GalN) and LPS-induced acute liver failure (ALF). SD rats were randomly divided into three groups: control group, P5 hUC-MSCs group, and P10 hUC-MSCs group. After transplantation, P5 hUC-MSCs provided a significant survival benefit. The analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) levels showed that transplantation with P5 hUC-MSCs was more effective than treatment with P10 hUC-MSCs. P5 hUC-MSCs also successfully downregulated the hepatic activity index (HAI) scores. Compared to P10 hUC-MSCs in vivo, P5 hUC-MSCs significantly enhanced the regeneration and inhibited the apoptosis of hepatocytes. CM-Dil-labeled hUC-MSCs were found to engraft within the recipient liver, whereas the homing of cells to the recipient liver in the P10 hUC-MSCs group was less effective compared to the P5 hUC-MSCs group. Previous studies have shown that the concentration of hepatocyte growth factor (HGF) in the injured liver was significantly increased. HGF is commonly known as the ligand of c-Met. The level of c-Met in hUC-MSCs as detected by Western blotting indicated that at a higher passage number, there is a decrease in c-Met. These data suggest that direct transplantation of P5 hUC-MSCs can more efficiently home to an injured liver. Subsequently, the P5 hUC-MSCs can rescue ALF and repopulate the livers of rats through the stimulation of endogenous liver regeneration and inhibition of hepatocellular apoptosis for compensated liver function, which is dependent on the higher level of c-Met than P10 hUC-MSCs.

Therapeutic Potential of Human Umbilical Cord–Derived Stem Cells in Ischemic Diseases

2007 ◽  
Vol 39 (5) ◽  
pp. 1620-1622 ◽  
Author(s):  
K.H. Wu ◽  
B. Zhou ◽  
X.M. Mo ◽  
B. Cui ◽  
C.T. Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Umbilical Cord ◽  
Therapeutic Potential ◽  
Human Umbilical Cord ◽  
Ischemic Diseases
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