Umbilical Cord Stem Cells
In contrast, stem cells recovered postnatally from the umbilical cord, including the umbilical cord blood cells, amnion/placenta, umbilical cord vein, or umbilical cord matrix cells, are a readily available and inexpensive source of cells that are capable of forming many different cell . Umbilical cord blood (UCB) stem cells are hematopoietic stem cells (HSC) that are recovered from the blood of the umbilical cord and placenta after birth. Umbilical cord blood is rich in cells that express the CD34 molecule, a surface protein that identifies cells as stem cells. Prior to the discovery of UCB stem cells, it was standard procedure to discard the umbilical cord and placenta; now much .
PDF Version: Riggan. To learn more about the benefits of becoming a member click here. Umbilical cords have traditionally been viewed as disposable how to calculate cubic yards of mulch by-product.
Cord blood, however, is rich in multi-potent hematopoietic stem cells HSCs. Recent medical advances have indicated that these stem cells found in cord blood can be used to treat the same disorders as the hematopoietic stem cells found in bone marrow and in the bloodstream but without some of the disadvantages of these types of transplants.
Cord blood is currently used to treat approximately 70 diseases including leukemias, lymphomas, anemias, and Severe Combined Immunodeficiency SCID. Six thousand patients worldwide have been treated with cord blood stem cell transplants, although the FDA considers the procedure to be experimental. These multipotent stem cells also show promise for the treatment of a variety of diseases and disorders other than those affecting the blood. Up to mL of blood can be taken what is umbilical cord stem cell research an umbilical cord for use in stem cell transplants.
Due to the experimental nature of cord blood transplants, such transplants are considered on a case-by-case basis. This blood is collected from the umbilical cord, processed,  and cryogenically preserved shortly after the umbilical cord is clamped. This blood can be cryogenically preserved for public or private family use. Public registries store cord blood donated for availability to the general public for transplantation. Private registries store cord blood on behalf of families who wish to use this blood for the donor infant, siblings, or other family members.
Donors from ethnic minority patients are particularly in need due to the greater variation of HLA-types in non-Caucasian ethnicities. Thirty-five percent of cord blood units go to patients of diverse ethnic and racial backgrounds. Cord blood does not have to be as closely matched as bone marrow or peripheral blood transplants.
For patients with uncommon tissue types, cord blood may be an option if a suitable adult donor cannot be found. Since cord blood is cryogenically preserved and stored, it is more readily available than bone marrow or peripheral blood from an unrelated donor, allowing transplants to take place within a shorter period of time. It takes approximately two weeks to locate, transfer, and thaw a preserved cord blood unit. Finding a suitable bone marrow donor typically takes at least two months.
This can be a potentially life threatening complication. The risk for developing GVHD is lower with cord blood transplants than with marrow or peripheral blood transplants. Cord blood also is less likely to transmit certain viruses such as cytomegalovirus CMVwhich poses serious risks for transplant patients with compromised immune systems. While the transplantation of cord blood has its advantages, its main disadvantage is the limited amount of blood contained within a single umbilical cord.
Because of this, cord blood is most often transplanted in children. Physicians are currently trying to determine ways that cord blood can be used in larger patients, such as transferring two cord blood units or increasing the number of cells in vitro before transplanting to the patient. It also takes longer for cord blood cells to engraft. This lengthier period means that the patient is at a higher risk for infection until the transplanted cells engraft. Patients also cannot get additional donations from the same donor if the cells do not engraft or if how to properly clean a coffee maker patient relapses.
If this is the case, an additional cord blood unit or an adult donor may be used. While cord blood is screened for a variety of common genetic diseases, rare genetic diseases that manifest after birth may be passed on. The National Cord Blood Program estimates that the risk of transmitting a rare genetic disorder is approximately 1 in 10, In addition to the use of cord blood stem cells for transplantation, cord blood stem cells are currently being investigated for use in stem cell therapy.
Cord blood stem cells are multipotent and are believed to have greater plasticity the ability to form into different stem cell types than adult hematopoietic stem cells found in bone marrow. HSCs are being investigated for use in autoimmune diseases such as diabetes, rheumatoid arthritis, and systemic lupus erythermatosis SLE in order to reprogram or reconstitute the immune system.
Additionally, research is being conducted on differentiating HSCs into other tissue types such as skeletal and cardiac muscle, liver cells hepatocytesand neurons. HSCs are currently being used in gene therapy, due to their self-renewing properties, as a means of delivering genes to repair damaged cells.
HSCs are the only cells currently being used in this manner in clinical gene therapy trials. In addition to the benefits related to transplanting HSCs derived from cord blood, HSCs are relatively easy to isolate, giving them an advantage over other adult stem cell types.
The limits and possibilities of using HSCs to repair tissues and treat non-blood related disorders are currently being studied. Similar to transplantation, the main disadvantage is the limited number of cells that can be procured from a single umbilical cord. Different ways of growing and multiplying HSCs in culture are currently being investigated. Immunologic rejection is a possibility, as with any stem cell transplant.
HSCs that are genetically modified are susceptible to cancerous formation and may not migrate home to the appropriate tissue and actively divide. The longevity of cord blood HSCs is also unknown. Cord blood stem cells are classified as adult or i dont know what i need stem cells.
Embryonic stem cells ESC are believed to be more advantageous for the treatment of disease or injury due to their pluripotent nature; that is, they have the ability to differentiate into all the cells present in the human body derived from the three germ layers endoderm, mesoderm, and ectoderm.
In the procurement of embryonic stem cells for research, the embryo from which the cells are harvested is destroyed. For those who believe that human life begins at conception this research is obviously unethical.
In contrast, adult stem cells can be how to implement ftp in java from tissue from a consenting patient. While cord blood stem cells are classified as adult stem cells, they appear to have greater potency ability to differentiate into other cell types than other adult stem cells, making them a potentially valuable option for use in a variety of treatments and therapies.
Cord blood stem cells offer some of the advantages of ESCs without any of the ethical drawbacks. Research into the use of cord blood stem cells for the treatment of disease and disability is a promising and ethical avenue of stem cell research. In the public arena there has been much discussion on the benefits of for-profit private cord blood banking over public banking.
Numerous for-profit companies offer new parents the option of collecting and storing cord blood for future use by the donor infant, siblings, or other family members. While many diseases can be treated with a cord blood transplant, most require stem cells from another donor allogeneic.
Cord blood cells taken from the patient autologous typically contain the same defect or precancerous cells that caused the patient to need the transplant in the first place.
Most medical professionals believe the chance that cord blood banking will be utilized by the patient or a close relative is relatively low. Estimates range from 1 out of 1, to 1 out ofThe American Academy of Pediatrics has discouraged cord blood banking for self-use, since most diseases requiring stem cell transplants are already present in the cord blood stem cells.
From the responses of 93 transplant physicians, in only 50 cases was privately banked blood used. In 9 of these cases the cord blood was transplanted back into the donor patient autologous transplant. There is no significant opposition in the medical community to the public banking of cord blood. The donation of cord blood to public banks has generally been encouraged by the medical profession.
The American Academy of Pediatrics encourages the public donation of cord blood with appropriate genetic and infectious disease testing, although they caution that parents should be notified that they will receive the results of this testing. They also recommend that parents be informed that publicly banked cord blood may not be available for future private use. One oft cited argument against cord blood banking is what is umbilical cord stem cell research it is not known how long these cells can remain viable in storage.
While it is not known if cells taken from an individual as an infant will be beneficial to them as an adult, units stored for up to 10 years have been transplanted successfully. This indicates that there is no reason to suggest serious deterioration in the quality of cord blood units stored for longer periods of time. Lubin, and William T. Lee, Stella M. Skip how to refinish concrete driveway main content.
Search form Search. Stem Cell Research. What are they? Use of Cord Blood in Transplants Up to mL of blood can be taken from an umbilical cord for use in stem cell transplants. What are the advantages? What are the disadvantages? What are the potentials for use in stem cell therapy? Embryonic Stem Cells Cord blood stem cells are classified as adult or non-embryonic stem cells. Private vs. Public Banking In the public arena there has been much discussion on the benefits of for-profit private cord blood banking over public banking.
References  During the processing stage excess red blood cells and plasma are removed reducing the volume to approximately 20 mL. Special Resource Types:. Dignitas Article. Follow CBHD:.
May 14, · With over 12 years of research and development on umbilical cord lining stem cells (ULSCs), which have properties of mesenchymal stem cells, RESTEM has emerged as a major contributor to cell-based therapy treatments based on the unique properties of its patented cell technology. About Sanford Health. Jan 05, · Back in , stem cells were initially discovered in the blood of the umbilical cord, and called umbilical cord stem cells afterwards. Use of umbilical cord stem cells started in the late s when it was found the umbilical cord which is a discarded material has many useful cells that can be used instead of painful and complicated bone marrow transplantation. Since , umbilical cord blood has been used successfully to treat children with leukaemia, anaemias and other blood diseases. Researchers are now looking at ways of increasing the number of haematopoietic stem cells that can be obtained from cord blood, .
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. Many researchers consider the transplantation of mesenchymal stem cells MSCs to be the most effective tool for cell therapy, due to the simultaneous activation of multiple mechanisms paracrine, trophic, immunomodulatory, and differentiation , affecting all stages of the regeneration of damaged tissues.
Nevertheless, currently there is active research work regarding MSCs from other sources—adipose tissue, peripheral and umbilical cord blood, amniotic fluid, skin, dental pulp, synovium, umbilical cord tissue, placental complex, endometrium, and others. In fact, evidence has suggested that MSCs may be present virtually in any vascularized tissue throughout the whole body [ 1 ]. All these cell types meet the minimum criteria for MSCs but have significant differences in their features.
The umbilical cord develops from the yolk sac and allantois and becomes a conduit between the developing embryo or fetus and the placenta. This substance is made largely from glycosaminoglycans, especially hyaluronic acid and chondroitin sulfate.
Collagen fibers are the main fibrillary component, while elastic fibers are absent. The cell component is presented by mesenchyme-derived cells fibroblasts, myofibroblasts, smooth muscle cells, and mesenchymal stem cells [ 2 ]. Cross-section of the human umbilical cord is shown in Figure 1. In , umbilical cord blood was declared to be the source of hematopoietic stem and progenitor cells [ 4 ], and the remaining umbilical cord tissue was considered medical waste with no scientific value.
This point of view was completely revised in , when McElreavey et al. In , Wang et al. The new microenvironment changes the properties of migrating cells, which probably explains their differences from BM-MSCs [ 41 ]. The common explant method of isolating UC-MSCs involves mincing the umbilical cords into small fragments, which are then attached to a culture dish bottom from which the cells migrate.
One of the disadvantages of this method is that the fragments frequently float up from the bottom of the dish, thereby reducing the cell recovery rate.
In some protocols, a stainless steel mesh is used to protect the tissue from floating [ 44 ]. According to some reports, the explant method allows the selection of a cell fraction with higher proliferative potential [ 45 , 46 ], but a remarkable variation of cell phenotype expressions was distinguished compared to enzymatic digestion [ 47 , 48 ].
In a recent study, three explant culture methods and three enzymatic methods were compared. Immune phenotype and multilineage differentiation capacity did not differ significantly among six groups [ 49 ]. It was also found that UC-MSCs isolated by explant technique always reached proliferation arrest earlier, irrespective of initial population doubling times, but the mechanism explaining this effect is still unclear [ 50 ].
On the contrary, later studies showed that cells obtained from explants presented similar characteristics morphology, population doubling time, postthaw survival, differentiation capacity, and phenotype to those from enzymatic protocols [ 51 ].
It should be particularly noted that almost all culture laboratories use umbilical cords obtained after Caesarean sections, because vaginal delivery significantly increases the risk of contamination of primary biological material. Some researchers suppose that viable MSCs can only be isolated from fresh umbilical cord tissue, not from frozen tissue fragments [ 55 ]. According to another report, MSCs derived from frozen cord tissue exhibited decreased plating efficiency and increased doubling times but near equivalent maximum cell expansion compared with fresh cord tissue [ 56 ].
According to another report, typical CFU-F efficiency the ratio of number of cells forming colonies under clonal conditions and number of cells seeded directly after isolation for BM-MSCs ranged from 0. Importantly, according to recent data, each individual UC-MSCs sample exhibited different population doubling rates and reached senescence at different passages due to unique genetic and epigenetic profiles, irrespective of isolation protocol [ 50 ].
Since passage 7, the telomerase activity of UC-MSCs is significantly reduced; but cell karyotype is stable for at least 25 passages [ 22 , 62 ]. To date, the expression profile of surface markers and pluripotency markers of UC-MSCs has been investigated extensively Tables 1 and 2. In most studies, it has been shown that CD presents on UC-MSCs surface [ 2 , 7 — 9 ], and its expression is maintained during long-term cultivation at least 16 passages [ 63 ].
In , De Kock et al. Human UC-MSCs showed significant enrichment in functional gene classes involved in liver and cardiovascular system development and function compared to MSCs derived from adipose tissue, bone marrow, and skin [ 12 ]. The most significant differences were found for genes presented in Table 3. In , Hsieh et al. It was found that, for the two MSC types, there were no common genes among the top 50 known genes most strongly expressed!
Top 10 for UC-MSCs included genes encoding somatostatin receptor 1, member 4 of immunoglobulin superfamily, gamma 2 smooth muscle actin, reticulon 1, natriuretic peptide precursor B, keratin 8, desmoglein 2, oxytocin receptor, desmocollin 3, and myocardin. In vitro UC-MSCs showed very high differentiation capacity: these cells were able to differentiate into chondrocytes, adipocytes, osteoblasts, odontoblast-like cells, dermal fibroblasts, smooth muscle cells, skeletal muscle cells, cardiomyocytes, hepatocyte-like cells, insulin-producing cells, glucagon-producing cells, and somatostatin-producing cells, sweat gland cells, endothelial cells, neuroglia cells oligodendrocytes , and dopaminergic neurons [ 8 , 15 , 21 , 42 , 72 — 75 ].
In , it was found that under specific conditions UC-MSCs expressed markers of male germ-like cells and primordial-like germ cells; such a possibility had previously been shown only for embryonic stem cells ESCs or induced pluripotent stem cells [ 76 , 77 ]. Comparison of the differentiation potential of UC-MSCs and MSCs from other sources bone marrow and adipose tissue is the subject of numerous studies presented in Table 4.
UC-MSCs overexpressing hepatocyte growth factor HGF could differentiate into dopaminergic neuron-like cells secreting dopamine, tyrosine hydroxylase, and dopamine transporter [ 78 ] and promoted nerve fiber remyelination and axonal regeneration one week after transplantation in rats with collagenase-induced intracerebral hemorrhage [ 30 ]. UC-MSCs from preeclamptic patients were more committed to neuroglial differentiation: the protein expressions of neuronal MAP-2 and oligodendrocytic MBP markers were significantly increased in cells from preeclampsia versus gestational age-matched controls [ 80 ].
At the same time, preterm birth had no effect on neuronal differentiation of UC-MSCs when compared to term delivery [ 81 ] but led to a decrease in osteogenic potential [ 82 ]. Thus, impaired metabolism of the maternal organism during pregnancy has a significant impact on the biological properties of neonatal MSCs.
This fact should be taken into account when choosing a source of cells for clinical use. MSCs produce a variety of bioactive compounds that supply a paracrine mechanism for their therapeutic activity. Based on these and published data, the authors of the study believe that UC-MSCs could be precommitted to an ectodermal fate. In , Weiss et al. In vitro study supported five main conclusions: 1 UC-MSCs suppressed the proliferation of Con-A-stimulated rat splenocytes xenograft model or activated human peripheral blood mononuclear cells allogeneic model.
It is currently believed that the immunomodulatory activity of UC-MSCs is provided by the paracrine mechanism. Therefore, the removal of xenogeneic components of the culture medium is important for future clinical study design in regenerative and transplant medicine [ 95 ].
About ten years ago the unexpected observation that MSCs can rescue cells with nonfunctional mitochondria by the transfer of either mitochondria or mitochondrial DNA was made [ 96 ]. The observation had broad implications for the therapeutic potentials of MSCs because failure of mitochondria is an initial event in many diseases, particularly with ischemia and reperfusion of tissues [ 97 ]. Furthermore, cellular behaviors including attachment-free proliferation, aerobic viability, and oxidative phosphorylation-reliant cellular motility were also regained after mitochondrial transfer by UC-MSCs.
The therapeutic effect of UC-MSCs-derived mitochondrial transfer was stably sustained for at least 45 passages [ 98 ]. The transfer of mitochondria therefore provided a rational for the therapeutic use of UC-MSCs for ischemic injury or diseases linked to mitochondrial dysfunction. Perinatal stem cells possess the characteristics of both embryonic stem cells and adult stem cells as they possess pluripotency properties, as well as multipotent tissue maintenance; they represent a bridge between embryonic and adult stem cells [ 99 ].
In one of the first works devoted to the subject, the tumor-producing capabilities of UC-MSCs were compared with human ESCs using the immunodeficient mouse model. Animals that received human ESCs developed teratomas in 6 weeks s. No animal that received human UC-MSCs developed tumors or inflammatory reactions at the injection sites when maintained for a prolonged period 20 weeks [ ].
Moreover, it was shown that UC-MSCs could be immortalized by transduction with a lentiviral vector carrying hTERT human telomerase reverse transcriptase catalytic subunit gene but even then transfected UC-MSCs showed no transformation into tumors in nude mice [ ].
Promising results were obtained in recent preclinical studies regarding the use of UC-MSCs for the treatment of different diseases using animal models.
Table 5 shows the most interesting data. Reports from the early period of MSC-based cell therapy for tissue repair demonstrated that injected MSCs may survive, engraft, and differentiate into specific cell types and repair injured tissues.
However, subsequent studies supported the notion that the level of UC-MSCs engraftment in the host organs of recipient animals was low after systemic administration and rather high after local administration. There is little evidence for the differentiation of UC-MSCs into relevant cells; it may be related to xenogeneic transplantation used in most of the studies. Presently, proposed mechanisms of UC-MSCs therapeutic activity include trophic and paracrine effects on cells of the immune system, remodeling of the extracellular matrix, angiogenesis, apoptosis, and stimulation of the migration and proliferation of resident progenitor cells [ 18 , 19 , 21 — 29 , 31 , ].
Currently, the FDA has registered dozens of clinical trials phases 1—3 on the safety and efficacy of allogeneic unmodified UC-MSCs transplantation for the treatment of socially significant diseases. At present, the results of only a small part of the clinical studies are published.
Table 6 shows the most promising results of clinical trials phases In all clinical studies UC-MSCs administration had no side-effects except for several cases of fever. This can be explained quite simply: UC-MSCs banking started a few years ago, so a set of recipient groups for autologous transplantation is not possible for the present. However, there is evidence that the efficacy of autologous and allogeneic MSCs transplantation is comparable [ — ].
The results of clinical trials using UC-MSCs are encouraging, particularly for treatment of autoimmune and endocrine diseases. The main problem with comparing the results of experimental studies and clinical trials is the lack of a standardized protocol for the isolation, expansion, and cryopreservation of UC-MSCs [ 42 ] and of uniform requirements for the final product.
Currently, UCX cells are being used as an active substance for the production of several off-the-shelf biopharmaceutical medicines at the point of initiating clinical trials. Due to the properties demonstrated in vitro and in vivo , UC-MSCs have attracted the attention not only of the experimental groups but also of clinicians.
It is no wonder that biobanks that had specialized previously only in umbilical cord blood storage introduced a new type of service, the storage of cultured MSCs from umbilical cord tissue.
Among these biobanks, there are Cryo-Cell International, Inc. The only restriction is that biomaterial must be obtained by Caesarean section; the total number of stored samples exceeds tens of thousands [ ].
It is considered that long-term cryopreservation does not change the biological properties of UC-MSCs [ ]. From our point of view, the optimal solution in terms of future clinical use is simultaneous banking of cord blood as a source of hematopoietic stem cells [ 4 ] and cultured MSCs from umbilical cord tissue [ ]. The human umbilical cord is a source of MSCs that have i a unique combination of prenatal and postnatal MSCs properties; ii no ethical problems with obtaining biomaterial; iii significant proliferative and differentiation potential; iv lack of tumorigenicity; v karyotype stability; vi high immunomodulatory activity.
Currently isolated and cultured umbilical cord MSCs are a promising storage object of the leading biobanks of the world, and the number of registered clinical trials on their use is currently growing. Timur Fatkhudinov and Irina Arutyunyan outlined, edited, and revised the paper and all authors read and approved the final paper. This research was supported by Russian Science Foundation, Project no.
The authors thank Irina Teveleva for final editing. They acknowledge Marina Tumkina for help with paper preparation. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Journal overview. Special Issues. Academic Editor: Salvatore Scacco. Received 27 Apr Accepted 14 Jul Published 29 Aug Abstract 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.
Introduction Many researchers consider the transplantation of mesenchymal stem cells MSCs to be the most effective tool for cell therapy, due to the simultaneous activation of multiple mechanisms paracrine, trophic, immunomodulatory, and differentiation , affecting all stages of the regeneration of damaged tissues.
The Origin and Morphology of the Human Umbilical Cord The umbilical cord develops from the yolk sac and allantois and becomes a conduit between the developing embryo or fetus and the placenta.
<- What is the purpose of using salt detergent solution - What is a legal shield associate->