crypto-exchange.tradetoolsfx.com/components/19.php This simplicity has opened the use of SNs to almost any laboratory in cell and molecular biology. All these GE technologies have opened up the possibility to obtain almost any mutation in any cell type. The PID patient has been treated classically by allogeneic HSCs transplantation or by the correction of the patient's own HSCs by the insertion of a functional copy of the affected gene by a viral vector [ 52 , 53 ]. The low frequency of these disorders and the difficulties to obtain HSCs from the patients preclude the use of patient HSCs as standard tools for disease modeling and preclinical testing.
However, this is only possible when a matched donor is available, making the development of gene therapy using autologous HSCs a highly desirable alternative [ 55 ]. In order to improve the gene therapy treatment for this rare disease, a model was required. Finally, it is noteworthy to mention that the gene editing approach using stem cells was used not only for disease modeling but also for disease treatment.
We also mentioned the problems this strategy face if we want to extend its use to model any disease [ 43 ]. This strategy has the additional advantage of count with isogenic hESCs that only differed in the mutation and are otherwise genetically identical. Then, we will describe some examples of how different groups have used GE to model different diseases:. Chromosomal translocations are signatures of numerous cancers and lead to expression of fusion genes that act as oncogenes. This aberrant translocation can be induced using gene editing tools in vitro in hESCs.
Monogenetic diseases. Disrupting a single gene by GE is easier than promoting translocations or multiple gene mutations. Human cellular models of monogenetic diseases were the first to be generated by GE as an alternative to iPSCs from patients. An elegant demonstration of the importance of using isogenic cell lines to model disease was provided by Reinhardt et al [ 60 ]. In addition, they used GE to correct the mutation generating isogenic cell lines that only differed in the LRRK2 mutation.
Rather, one of the healthy lines clustered closely to a mutant line and one healthy line was very different to all of the other lines. Interestingly, the only cell lines that clustered close together were pairs of mutant lines with and without correction of the mutation by GE. Other good examples of the relevance of using isogenic cell lines were showed by Li et al [ 61 ] and by our group [ 62 ].
In a stem cell transplant, stem cells are first Then, those mature cells replace tissue that is damaged by disease or injury. impact on human health without transplanting a single cell. Stem cells may therefore be very useful as a therapy for diseases in in human have been done to repair damaged eyes with cells derived.
MECP2 mutant neurons mimic the defects observed in this disorder and unbiased global gene expression analyses thanks to the use of isogenic cell lines showed that MECP2 protein functions as a global gene activator in neurons but not in neural precursors. Using these models, we uncovered that the absence of WAS protein also affected early hematopoiesis and megakaryocyte development, a phenotype that could not be observed when using iPSCs from WAS patients [ 63 ].
Only heterozygous population could be obtained. Summary of pluripotent stem cells and gene editing tools to generate human disease models. Schematic representation of the generation of iPSCs for drug screening, disease modeling and therapy.
As mentioned before, iPSCs can be obtained from any patient representing very potent tools for disease modeling. However, several considerations should be taken into account when interpreting the phenotypes of iPSCs from patients and controls since they have different genetic backgrounds.
Then, we will describe some examples of modeling human disease using this approach:. The authors demonstrated that TALENs could be used to generate disease models associated with chromosomal rearrangements [ 66 ]. Antibodies against the human platelet alloantigens HPAs cause severe alloimmune bleeding disorders.
Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers. Login to your personal dashboard for more detailed statistics on your publications. Edited by Minoru Tomizawa. Edited by Ali Gholamrezanezhad.
We are IntechOpen, the world's leading publisher of Open Access books. Built by scientists, for scientists. Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. Downloaded: Abstract Human pluripotent stem cells PSCs in the form of human embryonic stem cells hESCs or induced pluripotent stem cells iPSCs are capable of growing indefinitely in vitro, maintaining their capacity to differentiate into the three primary germ layers: mesoderm, endoderm and ectoderm.
Introduction Disease models are an essential tool for elucidating the molecular basis of several pathologies, allowing the development of novel therapies. Disease modeling with human stem cells derived from patients The advantage of using human stem cells derived from patients is that they can be isolated at different stages of disease severity.
Human adult stem cells Adult stem cells are multipotent cells found in all adult tissues, and they participate in the physiological regeneration of the tissues where they belong. The adult stem cell better characterized and with better perspectives for use as human models of disease are the neural progenitor cells NPCs , mesenchymal stromal cells MSCs and the HSCs: 2. Neural progenitor cells NPCs comprise relatively undifferentiated cell population in the central nervous systems CNSs that give rise to a broad array of specialized cells, including neurons and glial cells.
Mesenchymal stromal cells MSCs represent another interesting alternative for disease modeling. Hematopoietic stem cells HSCs have the potential to give rise to all hematopoietic cells in vitro and are therefore a potential source to mimic diseases affecting the hematopoietic system including primary immunodeficiencies PIDs and autoimmune diseases. Then, we will describe some examples of how different groups have used GE to model different diseases: Cancer. Editing iPSCs for disease modeling. More Print chapter. How to cite and reference Link to this chapter Copy to clipboard. Available from:.
While there are a growing number of potential therapies being tested in clinical trials there are only a few stem cell therapies that have so far been approved by the FDA. Two therapies that CIRM provided early funding for have been approved. Those are:. Right now the most commonly used stem cell-based therapy is bone marrow transplantation. Blood-forming stem cells in the bone marrow were the first stem cells to be identified and were the first to be used in the clinic.
This life-saving technique has helped thousands people worldwide who had been suffering from blood cancers, such as leukemia. In addition to their current use in cancer treatments, research suggests that bone marrow transplants will be useful in treating autoimmune diseases and in helping people tolerate transplanted organs. Other therapies based on adult stem cells are currently in clinical trials. Until those trials are complete we won't know which type of stem cell is most effective in treating different diseases.
Read the top ten things to know about stem cell treatments from ISSCR Alan Lewis talks about getting an embryonic stem cell-based therapy to patients Many overseas clinics - and a growing number here in the U.
This phenomenon is called stem cell tourism and is currently a source of concern for reputable stem cell scientists. These predatory clinics are offering therapies that have not been tested to prove they are effective or even safe. In recent few years, some patients who visited those clinics have died, others have been left blind or had serious infections as a result of receiving unproven and untested stem cells.
Stem cells hold the potential to treat a wide range of diseases. However, the path from the lab to the clinic is a long one. Before testing those cells in a human disease, researchers must grow the right cell type, find a way to test those cells, and make sure the cells are safe in animals before moving to human trials. Find Out More: Hans Keirstead talks about hurdles in developing a new therapy One of the biggest hurdles in any stem cell-based therapy is coaxing stem cells to become a single cell type.
The vital process of maturing stem cells from one state to another type is called differentiation. Guiding stem cells to become a particular cell type has been fraught with difficulty. For example, stem cells growing in a developing embryo receive a carefully choreographed series of signals from the surrounding tissue. To create the same effect in the lab, researchers have to try and mimic those signals.
Add the signals in the wrong order or the wrong dose and the developing cells may choose to remain immature—or become the wrong cell type Many decades of research has uncovered many of the signals needed to properly differentiate cells. Other signals are still unknown. Many CIRM-funded researchers are attempting to differentiate very pure populations of mature cell types that can accelerate therapies. Find Out More: Mark Mercola talks about differentiating cells into adult tissues Once a researcher has a mature cell type in a lab dish, the next step is to find out whether those cells can function in the body.
For example, embryonic stem cells that have matured into insulin-producing cells in the lab are only useful if they continue producing insulin once transplanted inside a body. Likewise, researchers need to know that the cells can integrate into the surrounding tissue and not be rejected by the body.