Umbilical Cord as Prospective Source for Mesenchymal Stem 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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Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy

Expert Opinion on Biological Therapy ◽

10.1517/14712598.2015.1051528 ◽

2015 ◽

Vol 15 (9) ◽

pp. 1293-1306 ◽

Cited By ~ 51

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

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Application of Mesenchymal Stem Cells Derived From the Umbilical Cord Instead of Bone Marrow In Hematopoietic Stem Cells Transplantation.

Blood ◽

10.1182/blood.v116.21.4544.4544 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4544-4544

Author(s):

Ching-Tien Peng

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Acute Gvhd ◽

Conflicts Of Interest ◽

Ex Vivo ◽

Proliferative Potential ◽

Hematopoietic Stem ◽

Cell Based Therapy

Abstract Abstract 4544 Bone marrow-derived mesenchymal stem cells (BMMSCs) have been found to enhance engraftment of hematopoietic stem cell transplantation (HSCT), plus show effect against graft-versus host disease (GVHD) because of their immunosuppressive properties. However, harvesting these cells is an invasive and painful procedure. To substitute BMMSCs from alternative sources is necessary. We intravenously infused ex vivo-expanded third-party umbilical cord-derived mesenchymal stem cells (UCMSCs) obtained from a bank 8 times in 3 patients who developed severe, steroid-resistant acute GVHD after allogeneic HSCT. The acute GVHD improved with each infusion of UCMSCs. Besides, after cotransplantation of cord blood and UCMSCs in 5 patients, we found UCMSCs enhanced absolute neutrophil counts and platelet counts recovery. No adverse effects after UCMSCs infusions were noted. We also found that UCMSCs had superior proliferative potential and greater immunosuppressive effects than BMMSCs in vitro. This is the first report of UCMSCs in human clinical application. These findings suggest UCMSCs are effective in treating aGVHD and can enhance hematopoiesis after HSCT. Considering that they are not only easy to obtain but also proliferate rapidly, UCMSCs would be the ideal candidate for cell-based therapy, especially for diseases associated with immune responses because of their immunosuppressive effects. Disclosures: No relevant conflicts of interest to declare.

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

Cellular Physiology and Biochemistry ◽

10.1159/000481639 ◽

2017 ◽

Vol 43 (3) ◽

pp. 891-904 ◽

Cited By ~ 2

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.

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

Molecular Biology of the Cell ◽

10.1091/mbc.e04-07-0652 ◽

2005 ◽

Vol 16 (3) ◽

pp. 1491-1499 ◽

Cited By ~ 71

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.

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

BioMed Research International ◽

10.1155/2019/5871698 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 1

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.

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Dramatic differences in activity of purines metabolizing ecto-enzymes between mesenchymal stem cells isolated from human umbilical cord blood and umbilical cord tissue

Biochemistry and Cell Biology ◽

10.1139/bcb-2013-0050 ◽

2013 ◽

Vol 91 (6) ◽

pp. 519-525 ◽

Cited By ~ 6

Author(s):

Katarzyna Roszek ◽

Katarzyna Bomastek ◽

Marian Drożdżal ◽

Michał Komoszyński

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Human Umbilical Cord Blood ◽

Proliferative Potential ◽

Human Umbilical Cord ◽

Isolation And Characterization ◽

Umbilical Cord Tissue

The high quality human mesenchymal stem cells (MSCs) with remarkable expansion potential in culture are demonstrated to possess multifold clinical applications. However, their isolation and characterization are difficult and sometimes ambiguous. We exploited nucleotide metabolizing ecto-enzymes for more complete characterization of MSCs. Using standard methods of cell culturing and analyses, we detected significant differences in the activity of ecto-nucleotidases on the surface of MSCs isolated from umbilical cord tissue and MSC-like cells derived from umbilical cord blood. Interestingly, the proliferation rate and the immunophenotypic characteristics of mesenchymal stem cells also correspond to the activities of these enzymes. Compared with the CD90-, CD105-, and CD73-deficient and slowly proliferating UCB-MSC-like cells that had relatively higher ecto-NTPDases activity, the CD90-, CD105-, and CD73-positive and rapidly proliferating UC-MSCs rather had ecto-5′-nucleotidase activity and presented neither ecto-nucleotidases nor adenylate kinase activities. In summary, our results demonstrate for the first time that activity of purine nucleotide metabolizing ecto-enzymes differs significantly between mesenchymal stem cells drawn from different neonatal sources, corresponding with a distinct proliferative potential.

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The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem Cells In Vitro

Cellular Physiology and Biochemistry ◽

10.1159/000438639 ◽

2016 ◽

Vol 38 (1) ◽

pp. 401-414 ◽

Cited By ~ 2

Author(s):

Wei Wang ◽

Xueyong Liu ◽

Wei Wang ◽

Jinghua Li ◽

Yuanyuan Li ◽

...

Keyword(s):

Stem Cells ◽

Flow Cytometry ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Indoxyl Sulfate ◽

Proliferative Potential ◽

Human Umbilical Cord ◽

Uremic Toxin ◽

Ki 67

Background/Aims: Indoxyl sulfate, an important protein-bound uremic toxin, can damage stem cells, thus hampering stem cell-based regenerative medicine approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical application because of their high proliferative potential and ease of isolation than MSCs from other sources. In the present study, we aimed to determine the harmful effects of indoxyl sulfate on the phenotype and functional potential of hUC-MSCs in vitro. Methods: The toxicity and cell viability was examined by Trypan blue exclusion and MTT assay. The cellular surface markers and the percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow cytometry. Proliferation was evaluated based on cell number counting and Ki-67 immunostaining. Cell senescence was measured using senescence-associated β-Galactosidase activity. The ability to stimulate the development of CD4+CD25+FoxP3+ regulatory T cells was assessed by incubating hUC-MSCs with peripheral blood mononuclear cells from the healthy volunteers. Results: Our results demonstrated that the immunophenotype of hUC-MSCs was not affected by indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers and fraction of Ki-67 positive proliferating cells, along with a significant increase in cellular senescence were detected in hUC-MSCs after exposure to indoxyl sulfate. Additionally, their ability to stimulate CD4+CD25+FoxP3+ regulatory T cell production was compromised when hUC-MSCs were pretreated with indoxyl sulfate. Conclusion: Taken together, our study clearly demonstrated that the molecular alterations and functional incompetence in hUC-MSCs under the challenge of indoxyl sulfate in vitro.

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

BioMed Research International ◽

10.1155/2013/438243 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 33

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.

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The Therapeutic Potential of Inflamed Gingiva-Derived Mesenchymal Stem Cells in Preclinical Studies: A Scoping Review of a Unique Biomedical Waste

Stem Cells International ◽

10.1155/2021/6619170 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Gamilah Al-Qadhi ◽

Sarah Al-Rai ◽

Layla Hafed

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Scoping Review ◽

Therapeutic Potential ◽

Fiber Formation ◽

Current Evidence ◽

Preclinical Studies ◽

Cell Based Therapy ◽

Scoping Reviews

Searching for considerable abundance, simple, and accessible sources in stem cell-based therapy opens the door for isolation of a new population of oral/dental stem cells known as inflamed gingiva-derived mesenchymal stem cells, which have recently come to light with promising therapeutic potential in tissue regenerative therapy. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines, this scoping review is aimed at highlighting the possible therapeutic potential of inflamed gingiva-derived mesenchymal stem cells in preclinical studies carried out to date and presenting the current evidence depends upon their comparison to the healthy gingiva-derived mesenchymal stem cells or other mesenchymal stem cell sources. A comprehensive electronic search using (PubMed, Embase, Scopus, and Web of Science) databases and a manual search of relevant references were conducted until June 2020. Included studies were assessed using a combination tool, including the guidelines for reporting preclinical in vitro studies on dental materials, which were based on the modification of the Consolidated Standards of Reporting Trial checklist and the guidelines for animal research: reporting of in vivo experiments. The initial research provided 360 articles, with 13 articles that met the inclusion criteria. While most of the included studies lacked randomization, blinding, and sample size calculation, they were designed accurately in other aspects of the guidelines. The results of this scoping review indicated that inflamed gingiva-derived mesenchymal stem cells could be effective in terms of osteogenic differentiation, collagen fiber formation, immunoregulation, migration capacity, and testing of dental material and may present a reliable alternative source for healthy gingiva-derived mesenchymal stem cells.

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