scholarly journals Human therapeutic cloning, pitfalls and lack luster because of rapid developments in induced pluripotent stem cell technology

2014 ◽  
Vol 8 (1) ◽  
pp. 5-10
Author(s):  
Song Hua ◽  
Henry Chung ◽  
Kuldip Sidhu

AbstractBackground: Therapeutic cloning is the combination of somatic cell nuclear transfer (SCNT) and embryonic stem cell (ES) techniques to create specific ES cells that match those of a patient. Because ES cells derived by nuclear transfer (SCNT ES cells) are genetically identical to the donor, it will not generate rejection by the host’s immune system and thus therapeutically may be more acceptable. Induced pluripotent stem cells (iPS) are a type of pluripotent stem cell artificially derived from an adult somatic cell by inducing a forced expression of a set of specific pluripotent genes. In the past few years, rapid progress in reprogramming and iPS technology has been made, and it seems to shadow any progress made in SCNT programs.Objective: This review compares the application perspective of SCNT with that of iPS in regenerative medicine.Methods:We conducted a literature search using the MEDLINE (PubMed), Wiley InterScience, Springer, EBSCO, and Annual Reviews databases using the keywords “iPS”, “ES”, “SCNT” “induced pluripotent stem cells”, “embryonic stem cells”, “therapeutic cloning”, “regenerative medicine”, and “somatic cell nuclear transfer”. Only articles published in English were included in this review.Results: These two methods both have advantages and disadvantages. Nevertheless, by using SCNT to generate patient-specific cell lines, it eliminates complications by avoiding the use of viral vectors during iPS generation. Success in in vitro matured eggs from aged women and even differentiation of oocytes from germ stem cells will further enhance the application of SCNT in regenerative medicine.Conclusion: Human SCNT may be an appropriate mean of generating patient stem cell lines for clinical therapy in the near future.

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Keiko Koga ◽  
Bo Wang ◽  
Shin Kaneko

Abstract In 2007, Human-induced pluripotent stem cells (iPSCs) were generated by transducing four genes (Oct3/4, Sox2, Klf4, c-Myc). Because iPSCs can differentiate into any types of cells in the body and have fewer ethical issues compared to embryonic stem (ES) cells, application of iPSCs for regenerative medicine has been actively examined. In fact, iPSCs have already been used for clinical applications, but at present, only autologous iPSC-derived grafts or HLA homozygous iPSC-derived grafts are being transplanted into patients following HLA matching. HLA is an important molecule that enables the immune system differentiates between self and non-self-components; thus, HLA mismatch is a major hurdle in the transplantation of iPSCs. To deliver inexpensive off-the-shelf iPSC-derived regenerative medicine products to more patients, it is necessary to generate universal iPSCs that can be transplanted regardless of the HLA haplotypes. The current strategy to generate universal iPSCs has two broad aims: deleting HLA expression and avoiding attacks from NK cells, which are caused by HLA deletion. Deletion of B2M and CIITA genes using the CRISPR/Cas9 system has been reported to suppress the expression of HLA class I and class II, respectively. Transduction of NK inhibitory ligands, such as HLA-E and CD47, has been used to avoid NK cell attacks. Most recently, the HLA-C retaining method has been used to generate semi-universal iPSCs. Twelve haplotypes of HLA-C retaining iPSCs can cover 95% of the global population. In future, studying which types of universal iPSCs are most effective for engraftment in various physiological conditions is necessary.


2021 ◽  
Vol 22 (9) ◽  
pp. 5011
Author(s):  
Daehwan Kim ◽  
Sangho Roh

Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since embryonic stem cells (ESCs) were established in mice, substantial efforts have been made to establish true ESCs in many species. Although various culture conditions were used to establish ESCs in cattle, the capturing of true bovine ESCs (bESCs) has not been achieved. In this review, the difficulty of establishing bESCs with various culture conditions is described, and the characteristics of proprietary induced pluripotent stem cells and extended pluripotent stem cells are introduced. We conclude with a suggestion of a strategy for establishing true bESCs.


Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Birbal Singh ◽  
Gorakh Mal ◽  
Vinod Verma ◽  
Ruchi Tiwari ◽  
Muhammad Imran Khan ◽  
...  

Abstract Background The global health emergency of COVID-19 has necessitated the development of multiple therapeutic modalities including vaccinations, antivirals, anti-inflammatory, and cytoimmunotherapies, etc. COVID-19 patients suffer from damage to various organs and vascular structures, so they present multiple health crises. Mesenchymal stem cells (MSCs) are of interest to treat acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection. Main body Stem cell-based therapies have been verified for prospective benefits in copious preclinical and clinical studies. MSCs confer potential benefits to develop various cell types and organoids for studying virus-human interaction, drug testing, regenerative medicine, and immunomodulatory effects in COVID-19 patients. Apart from paving the ways to augment stem cell research and therapies, somatic cell nuclear transfer (SCNT) holds unique ability for a wide range of health applications such as patient-specific or isogenic cells for regenerative medicine and breeding transgenic animals for biomedical applications. Being a potent cell genome-reprogramming tool, the SCNT has increased prominence of recombinant therapeutics and cellular medicine in the current era of COVID-19. As SCNT is used to generate patient-specific stem cells, it avoids dependence on embryos to obtain stem cells. Conclusions The nuclear transfer cloning, being an ideal tool to generate cloned embryos, and the embryonic stem cells will boost drug testing and cellular medicine in COVID-19.


Author(s):  
Fariha Khaliq

Stem cell therapy is an approach to use cells that have the ability of self-renewal and to differentiate into different types of functional cells that are obtained from embryo and other postnatal sources to treat multiple disorders. These cells can be differentiated into different types of stem cells based on their specific characteristics to be totipotent, unipotent, multipotent or pluripotent. As potential therapy, pluripotent stem cells are considered to be the most interesting as they can be differentiated into different type of cells with similar characteristics as embryonic stem cells. Induced pluripotent stem cells (iPSCs) are adult cells that are reprogrammed genetically into stem cells from human fibroblasts through expressing genes and transcription factors at different time intervals. In this review, we will discuss the applications of stem cell therapy using iPSCs technology in treating neurodegenerative disorder such that Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS). We have also broadly highlighted the significance of pluripotent stem cells in stem cell therapy.


2021 ◽  
pp. 75-89
Author(s):  
Jonathan Slack

‘Tissue-specific stem cells’ explores tissue-specific stem cells, which are stem cells found in the postnatal body that are responsible for tissue renewal or for repair following damage. Tissue-specific stem cells share with pluripotent stem cells the same ability to persist indefinitely as a population, to reproduce themselves, and to generate differentiated progeny cells. However, tissue-specific stem cells share few molecular characteristics with embryonic stem (ES) cells or induced pluripotent stem cells (iPS cells), such as expression of specific transcription factors or cell surface molecules. Only renewal tissues have stem cells in the sense of a special population of cells that reproduce themselves and continue to generate differentiated progeny.


eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ricardo Antonio Rosselló ◽  
Chun-Chun Chen ◽  
Rui Dai ◽  
Jason T Howard ◽  
Ute Hochgeschwender ◽  
...  

Cells are fundamental units of life, but little is known about evolution of cell states. Induced pluripotent stem cells (iPSCs) are once differentiated cells that have been re-programmed to an embryonic stem cell-like state, providing a powerful platform for biology and medicine. However, they have been limited to a few mammalian species. Here we found that a set of four mammalian transcription factor genes used to generate iPSCs in mouse and humans can induce a partially reprogrammed pluripotent stem cell (PRPSCs) state in vertebrate and invertebrate model organisms, in mammals, birds, fish, and fly, which span 550 million years from a common ancestor. These findings are one of the first to show cross-lineage stem cell-like induction, and to generate pluripotent-like cells for several of these species with in vivo chimeras. We suggest that the stem-cell state may be highly conserved across a wide phylogenetic range.


2009 ◽  
Vol 21 (1) ◽  
pp. 37 ◽  
Author(s):  
Ching-Chien Chang ◽  
Li-Ying Sung ◽  
Tomokazu Amano ◽  
X. Cindy Tian ◽  
Xiangzhong Yang ◽  
...  

Somatic cells can be reprogrammed to a totipotent state through nuclear transfer or cloning, because it has been demonstrated that the oocyte has the ability to reprogramme an adult nucleus into an embryonic state that can initiate the development of a new organism. Therapeutic cloning, whereby nuclear transfer is used to derive patient-specific embryonic stem cells, embraces an entire new opportunity for regenerative medicine. However, a key obstacle for human therapeutic cloning is that the source of fresh human oocytes is extremely limited. In the present review, we propose prospective sources of human oocytes by using oocyte cryopreservation, such as an oocyte bank and immature oocytes. We also address some potential issues associated with nuclear transfer when using cryopreserved oocytes. In the future, if the efficacy and efficiency of cryopreserved oocytes are comparable to those of fresh oocytes in human therapeutic cloning, the use of cryopreserved oocytes would be invaluable and generate a great impact to regenerative medicine.


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