HYPERGLYCEMIA REVERSAL IN DIABETIC INFARCTED RAT POSTINTRAVENOUS INFUSION OF HUMAN MESENCHYMAL STEM CELLS

2021 ◽  
pp. 1-5
Author(s):  
Sara Jabeen ◽  
Usha Gupta ◽  
Aleem Ahmed Khan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Single Dose ◽  
Blood Glucose ◽  
Human Umbilical Cord ◽  
Double Dose ◽  
Β Cells ◽  
Insulin Levels ◽  
Cell Based Therapy ◽  
Animal Survival

INTRODUCTION Hyperglycemia reversal and preservation/restoration of β-cells function in diabetic infarction remains as an attractive and challengeable therapeutic target. Mesenchymal stem cells (MSCs) are multipotent cells with a strong immunoregulatory potential that have emerged as a possible cell-based therapy for a variety of immunological diseases. The objective of this study was to examine the dose-dependent efcacy of intravenous administration of human umbilical cord blood derived MSCs (UCB-MSCs) in chemically induced rats with diabetic infraction. METHODS Wister rats (weight: 200-250g, males) received intraperitoneal streptozotocin injection followed by isoproterenol to develop diabetes infarction condition. After model development animals received intravenous single or double dose of human 6 UCB-MSCs (5 X 10 cells per animal at each dose) and followed up to 30 days post-administration. Pancreatic tissue histology, blood glucose and insulin levels were measured, and proportion of animal survival was calculated using Kaplan-Meier curve analysis. RESULTS Double dose of MSCs infusion resulted in reorganization of islet cells and partial restoration of β-cells at day 30. Comparatively faster restoration of glucose and insulin normalization was observed for two MSCs doses compared to single dose. Highest proportion of animal survival was observed (>85%) for double doses of MSCs infusion compared to single dose (>70%) at day 30. CONCLUSION Two consecutive intravenous doses of human UCB-MSCs can improve structural and functional decits of pancreatic tissues and maintain blood glucose and insulin levels in diabetic infarcted rats up to 30 days. However, identication of long-term effects entails longer follow-up periods, and larger sample sizes with other investigations.

Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy

2015 ◽  
Vol 15 (9) ◽  
pp. 1293-1306 ◽  
Author(s):  
Tan Li ◽  
Mingxu Xia ◽  
Yuanyuan Gao ◽  
Yanting Chen ◽  
Yun Xu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

scholarly journals Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells

2017 ◽  
Vol 43 (3) ◽  
pp. 891-904 ◽  
Author(s):  
Jie He ◽  
Guang-ping Ruan ◽  
Xiang Yao ◽  
Ju-fen Liu ◽  
Xiang-qing Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Intravenous Infusion ◽  
Dose Group ◽  
High Dose ◽  
Human Umbilical Cord ◽  
Cynomolgus Monkeys ◽  
Cell Based Therapy

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3+ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 107/kg, which is 10 times of that in clinical human use.

scholarly journals Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking Pathway

2005 ◽  
Vol 16 (3) ◽  
pp. 1491-1499 ◽  
Author(s):  
Masanori Terai ◽  
Taro Uyama ◽  
Tadashi Sugiki ◽  
Xiao-Kang Li ◽  
Akihiro Umezawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Life Span ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Future Application ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to serve as an excellent alternative to bone marrow-derived human mesenchymal stem cells. However, it is difficult to study them because of their limited life span. To overcome this problem, we attempted to produce a strain of UCBMSCs with a long life span and to investigate whether the strain could maintain phenotypes in vitro. UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span. The UCBMSCs underwent 30 population doublings (PDs) and stopped dividing at PD 37. The UCBMSCs newly established with hTERT (UCBTERTs) proliferated for >120 PDs. The p16INK4a/RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16INK4a/RB pathway. The characteristics of the UCBTERTs remained unchanged during the prolongation of life span. UCBTERTs provide a powerful model for further study of cellular senescence and for future application to cell-based therapy by using umbilical cord blood cells.

scholarly journals Cell-to-Cell Culture Inhibits Dedifferentiation of Chondrocytes and Induces Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xingfu Li ◽  
Yujie Liang ◽  
Xiao Xu ◽  
Jianyi Xiong ◽  
Kan Ouyang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Cartilage Damage ◽  
Great Promise ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Contact ◽  
Human Umbilical Cord ◽  
Low Density ◽  
Cell Based Therapy

Background. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess great promise as a therapeutic to repair damaged cartilage. Direct intra-articular injection of mesenchymal stem cells has been shown to reduce cartilage damage and is advantageous as surgical implantation and associated side effects can be avoided using this approach. However, the efficacy of stem cell-based therapy for cartilage repair depends highly on the direct interactions of these stem cells with chondrocytes in the joint. In this study, we have carried out an in vitro cell-to-cell contact coculture study with human articular chondrocytes (hACs) and hUC-MSCs, with the goal of this study being to evaluate interactions between hACs and hUC-MSCs. Methods. Low-density monolayer cultures of hUC-MSCs and hACs were mixed at a ratio of 1 : 1 in direct cell-to-cell contact groups. Results were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Results. A mixed coculture of hUC-MSCs and hACs was found to exhibit synergistic interactions with enhanced differentiation of hUC-MSCs and reduced dedifferentiation of chondrocytes. Mixed cultures after 21 days were found to exhibit sufficient chondrogenic induction. Conclusions. The results from this study suggest the presence of mutual effects between hUC-MSCs and hACs even culture at low density and provide further support for the use of intra-articular injection strategies for cartilage defect treatment.

scholarly journals Side-by-Side Comparison of the Biological Characteristics of Human Umbilical Cord and Adipose Tissue-Derived Mesenchymal Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Li Hu ◽  
Jingqiong Hu ◽  
Jiajia Zhao ◽  
Jiarong Liu ◽  
Weixiang Ouyang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Umbilical Cord ◽  
Human Adipose Tissue ◽  
Cell Types ◽  
Human Umbilical Cord ◽  
Cell Based Therapy ◽  
Secretion Profile ◽  
Immunological Phenotype

Both human adipose tissue-derived mesenchymal stem cells (ASCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been explored as attractive mesenchymal stem cells (MSCs) sources, but very few parallel comparative studies of these two cell types have been made. We designed a side-by-side comparative study by isolating MSCs from the adipose tissue and umbilical cords from mothers delivering full-term babies and thus compared the various biological aspects of ASCs and UC-MSCs derived from the same individual, in one study. Both types of cells expressed cell surface markers characteristic of MSCs. ASCs and UC-MSCs both could be efficiently induced into adipocytes, osteoblasts, and neuronal phenotypes. While there were no significant differences in their osteogenic differentiation, the adipogenesis of ASCs was more prominent and efficient than UC-MSCs. In the meanwhile, ASCs responded better to neuronal induction methods, exhibiting the higher differentiation rate in a relatively shorter time. In addition, UC-MSCs exhibited a more prominent secretion profile of cytokines than ASCs. These results indicate that although ASCs and UC-MSCs share considerable similarities in their immunological phenotype and pluripotentiality, certain biological differences do exist, which might have different implications for future cell-based therapy.

Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells Differentiate Into Insulin-Producing Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4578-4578
Author(s):  
Lian Ma ◽  
Hongwu Wang ◽  
Hongyan He ◽  
Limin Lin ◽  
Weizhong Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Blood Glucose ◽  
Umbilical Cord ◽  
Human Insulin ◽  
Diabetic Rats ◽  
Human Umbilical Cord ◽  
Survival Ratio ◽  
Rt Pcr ◽  
Insulin Producing Cells

Abstract Abstract 4578 Introduction Islet transplantation is an effective way of reversing type 1 diabetes. However, islet transplantation has been hampered by problems, such as immune rejection, and the scarcity of donor islets. Human Umbilical Cord Wharton's Jelly-derived Mesenchymal Stem Cells (huMSCs), which can be differentiated into insulin-producing cells could provide a source of cells for transplant. Methods Vitro Research We isolated and cultured huMSCs, and induced huMSCs differentiated into insulin-producing cells in the condition of islet cells grows. The morphology of huMSCs after induction were monitored by under inversion phase contrast microscope?GImmunocytochemical methods were used to detect the insulin and glucagon protein, and reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect Human insulin gene and PDX-1 gene. Dithizon-stained was used to detect zinc hydronium and radio-immunity was used to detect insulin level of culture supernatant.Vivo Research huMSCs were transplanted into the body of diabetic rats through vena caudalis, and then we observed the change of blood glucose?Abody weight ?Aserum insulin levels and survival ratio in STZ-induced diabetic rats. We detected human insulin by immunohistochemistry and RT-PCR. HE stain was used to detect the morphological changes of rat's pancreatic island. Results Vitro Research The morphology of huMSCs under medicine induction gradually changed from fibroblast to round and some of then had the tend of forming clusters.?GThe result of immunocytochemical showed that the expression of human insulin and glucagon was positive after treatment with medicine?GhuMSCs induced by medicine can express insulin and PDX-1 gene by RT-PCR?GDithizon stain show that the cytoplasm of huMSCs after induction were stained in Brownish red color?Gthe results of radio-immunity manifested that the insulin quantity secreted by medicine induction were significant differences compared with control group(t??6.183,P<0.05). Vivo Research When transplanted into Streptozotocin(STZ)-treated diabetics rats, huMSCs can decreased blood glucose, increased body weight and survival ratio in diabetic rats?GAfter being transplanted for one month, we discovered that it can be planted into rat's pancreas and liver by Hoechst33258?Gimmunohistochemistry and RT-PCR show that the pancreas of rat can express human insulin?Gthe morphology of rats' pancreatic island was repaired obviously if compared with diabetic rats before the transplantation through HE-stain. Conclusion huMSCs can be differentiated into insulin-producing cells in vitro or in vivo. Therefore, huMSCs have the potential to become an excellent candidate in β cell replacement therapy of diabetes. Disclosures: No relevant conflicts of interest to declare.

Homogeneity and heterogeneity of biological characteristics in mesenchymal stem cells from human umbilical cords and exfoliated deciduous teeth

2020 ◽  
Vol 98 (3) ◽  
pp. 415-425 ◽  
Author(s):  
Chao Yang ◽  
Yu Chen ◽  
Liwu Zhong ◽  
Min You ◽  
Zhiling Yan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ethical Issues ◽  
Adipogenic Differentiation ◽  
Neurite Growth ◽  
Biological Characteristics ◽  
Deciduous Teeth ◽  
Human Umbilical Cord ◽  
Cell Based Therapy ◽  
Umbilical Cords

Mesenchymal stem cells (MSCs) have proven powerful potential for cell-based therapy both in regenerative medicine and disease treatment. Human umbilical cords and exfoliated deciduous teeth are the main sources of MSCs with no donor injury or ethical issues. The goal of this study was to investigate the differences in the biological characteristics of human umbilical cord mesenchymal stem cells (UCMSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). UCMSCs and SHEDs were identified by flow cytometry. The proliferation, differentiation, migration, chemotaxis, paracrine, immunomodulatory, neurite growth-promoting capabilities, and acetaldehyde dehydrogenase (ALDH) activity were comparatively studied between these two MSCs in vitro. The results showed that both SHEDs and UCMSCs expressed cell surface markers characteristic of MSCs. Furthermore, SHEDs exhibited better capacity for proliferation, migration, promotion of neurite growth, and chondrogenic differentiation. Meanwhile, UCMSCs showed more outstanding adipogenic differentiation and chemotaxy. Additionally, there were no significant differences in osteogenic differentiation, immunomodulatory capacity, and the proportion of ALDHBright compartment. Our findings indicate that although both UCMSCs and SHEDs are mesenchymal stem cells and presented some similar biological characteristics, they also have differences in many aspects, which might be helpful for developing future clinical cellular therapies.

scholarly journals Umbilical Cord as Prospective Source for Mesenchymal Stem Cell-Based Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Irina Arutyunyan ◽  
Andrey Elchaninov ◽  
Andrey Makarov ◽  
Timur Fatkhudinov
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Current Evidence ◽  
Immunomodulatory Activity ◽  
Proliferative Potential ◽  
Human Umbilical Cord ◽  
Preclinical Studies ◽  
Cell Type ◽  
Cell Based Therapy

The paper presents current evidence on the properties of human umbilical cord-derived mesenchymal stem cells, including origin, proliferative potential, plasticity, stability of karyotype and phenotype, transcriptome, secretome, and immunomodulatory activity. A review of preclinical studies and clinical trials using this cell type is performed. Prospects for the use of mesenchymal stem cells, derived from the umbilical cord, in cell transplantation are associated with the need for specialized biobanking and transplant standardization criteria.

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