scholarly journals Conditioned medium derived from bovine umbilical mesenchymal stem cells as an alternative source of cell-free therapy

2021 ◽  
pp. 2588-2595
Author(s):  
Dwi Liliek Kusindarta ◽  
Hevi Wihadmadyatami

Umbilical cord blood (UCB) cells are an important source of mesenchymal stem cells (MSCs). It is known that the umbilical cord is rich in hematopoietic stem cells, which influenced research on ontogeny and transplantation (allogeneic transplantation). In recent years, stem cell research has emerged as an area of major interest due to its prospective applications in various aspects of both human and veterinary medicine. Moreover, it is known that the application of MSCs has several weaknesses. The use of these cells has limitations in terms of tumorigenesis effect, delivery, safety, and variability of therapeutic response, which led to the use of secretomes as an alternative to cell-free therapy. The main obstacle in its use is the availability of human UCB as an origin of MSCs and MSCs' secretomes, which are often difficult to obtain. Ethical issues regarding the use of stem cells based on human origin are another challenge, so an alternative is needed. Several studies have demonstrated that MSCs obtained from bovine umbilical cords have the same properties and express the same surface markers as MSCs obtained from human umbilical cords. Therefore, secretomes from MSCs derived from domestic animals (bovine) can possibly be used in human and veterinary medicine. This finding would contribute significantly to improve cell-free therapy. At present, the use of UCB MSCs derived from domestic animals, especially bovines, is very restricted, and only limited data about bovine UCB are available. Therefore, the aim of this review was to provide an updated overview of cell-free therapy and discuss the new possibilities introduced by the generation of this therapy derived from bovine umbilical MSCs as a promising tool in developing modern and efficient treatment strategies.

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Tania Sultana ◽  
Soojung Lee ◽  
Hun-Young Yoon ◽  
Jeong Ik Lee

Stem cell therapy has prompted the expansion of veterinary medicine both experimentally and clinically, with the potential to contribute to contemporary treatment strategies for various diseases and conditions for which limited or no therapeutic options are presently available. Although the application of various types of stem cells, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose tissue-derived mesenchymal stem cells (AT-MSCs), and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), has promising potential to improve the health of different species, it is crucial that the benefits and drawbacks are completely evaluated before use. Umbilical cord blood (UCB) is a rich source of stem cells; nonetheless, isolation of mesenchymal stem cells (MSCs) from UCB presents technical challenges. Although MSCs have been isolated from UCB of diverse species such as human, equine, sheep, goat, and canine, there are inherent limitations of using UCB from these species for the expansion of MSCs. In this review, we investigated canine UCB (cUCB) and compared it with UCB from other species by reviewing recent articles published from February 2003 to June 2017 to gain an understanding of the limitations of cUCB in the acquisition of MSCs and to determine other suitable sources for the isolation of MSCs from canine. Our review indicates that cUCB is not an ideal source of MSCs because of insufficient volume and ethical issues. However, canine reproductive organs discarded during neutering may help broaden our understanding of effective isolation of MSCs. We recommend exploring canine reproductive and adipose tissue rather than UCB to fulfill the current need in veterinary medicine for the well-designed and ethically approved source of MSCs.


2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
O. O. Maslova ◽  
N. S. Shuvalova ◽  
O. M. Sukhorada ◽  
S. M. Zhukova ◽  
O. G. Deryabina ◽  
...  

The object of the paper is to show the heterogeneity of 300 cord samples processed in the current research. The differences in effectiveness of mesenchymal stem cell (MSC) isolation are shown. Moreover, the recommendations for choosing the method of MSC isolation depending on the value of stromal-vascular rate are given. The data can be useful for selecting the optimal conditions to obtain MSC and for further cryopreservation of umbilical cord tissue.


2017 ◽  
Vol 4 (3) ◽  
Author(s):  
Ana G. Serrato López ◽  
Juan J. Montesinos Montesinos ◽  
Santiago R. Anzaldúa Arce

Mesenchymal stem cells (MSCs) have been isolated from the endometrium of humans, mice, cows, pigs and ewes. Typically, these cells are detected in the deep regions of the endometrium, closer to the union with the myometrium. MSCs possess characteristics such as clonogenicity and multipotentiality since they can differentiate in vitro into adipogenic, chondrogenic and osteogenic lineages. These cells can be induced to differentiate in vitro not only into the mesodermal lineage but also into the endodermal and ectodermal lineages. Therefore, MSCs show a great regenerative capacity for various organs and tissues, including the endometrium. Some advantages of endometrial MSCs compared with other MSC sources are their immune modulating activity, their ease of obtainment, and the amount of sample that may be collected. The study of endometrial MSCs in domestic animals is a new and promising field because increasing our understanding of the physiology and biology of these cells may lead to a better understanding of the physiopathology of reproductive diseases, and the development of treatment methods for infertility problems. In other veterinary medicine fields, MSCs can be used for the treatment of autoimmune diseases, cardiac affections, musculoskeletal and articular lesions, muscle degeneration, type 1 diabetes, urinary tract diseases, neurodegenerative processes and tumours. Finally, MSCs are also an important clinical tool for tissue engineering and regenerative medicine. The aim of this review is to present an updated outlook of the knowledge regarding endometrial MSCs and their possible applications in veterinary medicine.Figure 1: Immunoregulatory ability of MSCs. MSCs regulate the functions of NK cells, dendritic cells (DC) and T lymphocytes. The immunosuppressive effect may occur through the secretion of different factors or through cellular contact (black arrows). The former pathway involves TGFß, HGF, IL-10, PGE2, and HLA-G5, whereas the latter pathway involves the products of IDO enzyme activity, PD-L1, HLA-G1, ICAM-I and VCAM-I. Pro-inflammatory cytokines (IFN-?) secreted by NK cells and activated T lymphocytes favour the immunoregulatory activity of MSCs (dotted lines), because they increase or induce the secretion of molecules that regulate the functions of the distinct cellular components of the immune system. Modified from Montesinos et al, and Ma et al.19,66


2019 ◽  
Vol 120 (7) ◽  
pp. 12018-12026 ◽  
Author(s):  
Maryam Darvish ◽  
Zahra Payandeh ◽  
Fatemeh Soleimanifar ◽  
Behnaz Taheri ◽  
Masoud Soleimani ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4306-4306
Author(s):  
Lulu Lu ◽  
Yong-jun Liu ◽  
Zhen-shu Xu ◽  
Cun-gang Fan ◽  
Han Wang ◽  
...  

Abstract Mesenchymal stem cells (MSCs) have been isolated from venous endothelia and subendothelia of the human umbilical cord using a tedious procedure. We established a simple method to isolate abundant MSCs from human umbilical cord tissues (UC). 36 full-term umbilical cords were obtained. MSCs were isolated after enzyme digestion of minced cord fragments. The mean nucleated cells isolated from UC was 1.13±0.37×106/cm UC. A total of 1×10e10 MSCs was obtained after several passages over 4 weeks. CFU-F frequency is 1:1609. The population doubling time was approximately 28.02±10.53 h in passage 2 cells. The MSC cells were positive for CD13, CD29, CD44, SH-2, SH-3, CD166 and HLA class I (A, B, C), but were negative for CD34, CD38, CD45, CD31 and HLA-DR. More than 80% cells were in G0-G1 phase, whereas a small population of cells was engaged in proliferation (S+G2+M=9.16%). Under specified culture conditions, the MSC cells differentiated into adipocytes, osteoblasts and neural cells. The MSCs were also found to express cytokines of SCF, LIF, M-CSF, Flt3-ligand, IL-6, GM-CSF, G-CSF, VEGF, and SDF-1. When co-cultured with CD34+ cells from UC blood, the UC-derived MSCs were able to support the hematopoiesis of long-term culture-initiating cells. These findings suggested that abundant MSCs can be isolated simply and effectively from the whole cord tissue. Umbilical cords may be an attractive source of MSCs for tissue engineering, cord blood expansion and cord blood transplantation.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3650-3650
Author(s):  
Kent W. Christopherson ◽  
Tiki Bakhshi ◽  
Shamanique Bodie ◽  
Shannon Kidd ◽  
Ryan Zabriskie ◽  
...  

Abstract Hematopoietic Stem Cells (HSC) are routinely obtained from bone marrow, mobilized peripheral blood, and umbilical Cord Blood. Traditionally, adult bone marrow has been utilized as a source of Mesenchymal Stem Cells (MSC). Bone marrow derived MSC (BM-MSC) have previously been shown to maintain the growth of HSC obtained from cord blood and have been utilized for cord blood expansion purposes. However, the use of a mismatched BM-MSC feeder stromal layer to support the long term culture of cord blood HSC is not ideal for transplant purposes. The isolation of MSC from a novel source, the Wharton’s Jelly of Umbilical Cord segments, was recently reported (Romanov Y, et al. Stem Cells.2003; 21: 105–110) (Lee O, et al. Blood.2004; 103: 1669–1675). We therefore hypothesized that Umbilical Cord derived MSC (UC-MSC) have the ability to support the long term growth of cord blood derived HSC similar to that previously reported for BM-MSC. To test this hypothesis, MSC were isolated from the Wharton’s Jelly of Umbilical Cord segments and defined morphologically and by cell surface markers. UC-MSC were then tested for their ability to support the growth of pooled CD34+ cord blood cells in long term culture - initiating cell (LTC-IC) assays as compared to BM-MSC. We observed that like BM-MSC, CB-MSC express a defined set of cell surface markers. By flow cytometry we determined that that both UC-MSC and BM-MSC are positive for CD29, CD44, CD73, CD90, CD105, CD166, HLA-A and negative for CD45, CD34, CD38, CD117, HLA-DR expression. Utilizing Mitomycin C treated (200 μM, 15 min.) UC-MSC from multiple donors as a feeder layer we observed that UC-MSC have the ability to support the maintenance of long term hematopoiesis during the LTC-IC assay. Specifically, UC-MSC isolated from separate umbilical cord donors support the growth of 69.6±11.9 (1A), 31.7±3.9 (2B), 67.0±13.5 (3A), and 38.5±13.7 (3B) colony forming cells (CFC) per 1×104 CD34+ cord blood cells as compared to 64.0±4.2 CFC per 1×104 CD34+ cord blood cells supported by BM-MSC (Mean±SEM, N=4 separate segments from three different donors). Thus, Umbilical Cord derived Mesenchymal Stem Cells, a recently described novel source of MSC, have the ability to support long term maintenance of Hematopoietic Stem Cells, as defined by the LTC-IC assay. These results may have potential therapeutic application with respect to ex vivo stem cell expansion of Cord Blood Hematopoietic Stem Cells utilizing a Mesenchymal Stem Cell stromal layer. In addition, these data suggest the possibility of co-transplantation of matched Mesenchymal and Hematopoietic Stem Cells from the same umbilical cord and cord blood donor respectively. Lastly, these results describe a novel model system for the future study of the interaction between Cord Blood Hematopoietic Stem Cells and the appropriate supportive microenvironment represented by the Umbilical Cord - Mesenchymal Stem Cells.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4544-4544
Author(s):  
Ching-Tien Peng

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Claire Mennan ◽  
Karina Wright ◽  
Atanu Bhattacharjee ◽  
Birender Balain ◽  
James Richardson ◽  
...  

Umbilical cords as a source of stem cells are of increasing interest for cell therapies as they present little ethical consideration and are reported to contain immune privileged cells which may be suitable for allogeneic based therapies. Mesenchymal stem cells (MSCs) sourced from several different cord regions, including artery, vein, cord lining, and Wharton’s jelly, are described in the literature. However, no one study has yet isolated and characterised MSCs from all regions of the same cord to determine the most suitable cells for cell based therapeutics.


2016 ◽  
Vol 4 (2) ◽  
pp. 230-235 ◽  
Author(s):  
C. Nasadyuk

Due to the prominent immunosuppressive and regenerative properties, umbilical cord mesenchymal stem cells are the most widely explored in the treatment of autoimmune diseases and posttransplant complications as well as for the facilitation of engraftment of hematopoietic stem cell transplant and cell culturing in vitro. The review presents modern immunophenotypic characterization of the umbilical cord mesenchymal stem cells, approaches to isolation, biobanking, and clinical application.


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