scholarly journals Ethics of research on stem cells and regenerative medicine: ethical guidelines in the Islamic Republic of Iran

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Leila Afshar ◽  
Hamid-Reza Aghayan ◽  
Jila Sadighi ◽  
Babak Arjmand ◽  
Seyed-Mahmoud Hashemi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
National Committee ◽  
Ethical Guideline ◽  
Ethical Guidelines ◽  
Ethical Considerations ◽  
Ethics Of Research

Abstract Background Regenerative medicine plays a major role in biomedicine, and given the ever-expanding boundaries of this knowledge, numerous ethical considerations have been raised. Main text Rapid advancement of regenerative medicine science and technology in Iran, emerged the Iranian National Committee for Ethics in Biomedical Research to develop a comprehensive national ethical guideline. Therefore, the present ethical guideline which comprises eleven chapters was developed in 2019 and approved in early 2020. The titles of these chapters were selected based on the ethical considerations of various aspects of the field of regenerative medicine: (1) ethical principles of research on stem cells and regenerative medicine; (2) ethical considerations for research on stem cells (embryonic stem cells, epiblast stem cells, tissue-specific stem cells, stem cells derived from transdifferentiation, induced pluripotent stem cells [iPSCs], germline pluripotent stem cells, germline stem cells, and somatic cell nuclear transfer [SCNT] stem cells); (3) ethical considerations for research on somatic cells in regenerative medicine (adult somatic cells, fetal tissue somatic cells, and somatic cells derived from pregnancy products [other than fetus]); (4) ethical considerations for research on gametes in regenerative medicine; (5) ethical considerations for research related to genetic manipulation (human and animal) in regenerative medicine; (6) ethical considerations for research on tissue engineering in regenerative medicine; (7) ethical considerations for pre-clinical studies in regenerative medicine; (8) ethical considerations for clinical trials in regenerative medicine; (9) ethical considerations for stem cells and regenerative medicine bio-banks; (10) ethical considerations for privacy and confidentiality; and (11) ethical considerations for obtaining informed consent. Conclusion This article discusses the process of developing the present ethical guidelines and its practical points. We hope that it can play an important worldwide role in advancing ethics of research on stem cells and regenerative medicine.

scholarly journals Non-integrating Methods to Produce Induced Pluripotent Stem Cells for Regenerative Medicine: An Overview

2020 ◽  
Author(s):  
Immacolata Belviso ◽  
Veronica Romano ◽  
Daria Nurzynska ◽  
Clotilde Castaldo ◽  
Franca Di Meglio
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Safety Issues ◽  
Advantages And Disadvantages ◽  
Induced Pluripotent

Induced Pluripotent Stem cells (iPSC) are adult somatic cells genetically reprogrammed to an embryonic stem cell-like state. Due to their autologous origin from adult somatic cells, iPSCs are considered a tremendously valuable tool for regenerative medicine, disease modeling, drug discovery and testing. iPSCs were first obtained by introducing specific transcription factors through retroviral transfection. However, cell reprogramming obtained by integrating methods prevent clinical application of iPSC because of potential risk for infection, teratomas and genomic instability. Therefore, several integration-free alternate methods have been developed and tested thus far to overcome safety issues. The present chapter provides an overview and a critical analysis of advantages and disadvantages of non-integrating methods used to generate iPSCs.

scholarly journals Induced Tissue-Specific Stem Cells (iTSCs): Their Generation and Possible Use in Regenerative Medicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 780
Author(s):  
Issei Saitoh ◽  
Masahiro Sato ◽  
Yuki Kiyokawa ◽  
Emi Inada ◽  
Yoko Iwase ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Additional Treatment ◽  
Tissue Specific ◽  
Immunocompromised Mice ◽  
Tissue Specific Stem Cells

Induced tissue-specific stem cells (iTSCs) are partially reprogrammed cells which have an intermediate state, such as progenitors or stem cells. They originate from the de-differentiation of differentiated somatic cells into pluripotent stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or from the differentiation of undifferentiated cells. They show a limited capacity to differentiate and a morphology similar to that of somatic cell stem cells present in tissues, but distinct from that of iPSCs and ESCs. iTSCs can be generally obtained 7 to 10 days after reprogramming of somatic cells with Yamanaka’s factors, and their fibroblast-like morphology remains unaltered. iTSCs can also be obtained directly from iPSCs cultured under conditions allowing cellular differentiation. In this case, to effectively induce iTSCs, additional treatment is required, as exemplified by the conversion of iPSCs into naïve iPSCs. iTSCs can proliferate continuously in vitro, but when transplanted into immunocompromised mice, they fail to generate solid tumors (teratomas), implying loss of tumorigenic potential. The low tendency of iTSCs to elicit tumors is beneficial, especially considering applications for regenerative medicine in humans. Several iTSC types have been identified, including iTS-L, iTS-P, and iTS-D, obtained by reprogramming hepatocytes, pancreatic cells, and deciduous tooth-derived dental pulp cells, respectively. This review provides a brief overview of iPSCs and discusses recent advances in the establishment of iTSCs and their possible applications in regenerative medicine.

scholarly journals Induction of functional hypothalamus and pituitary tissues from pluripotent stem cells for regenerative medicine

2020 ◽  
Author(s):  
Mayuko Kano ◽  
Hidetaka Suga ◽  
Hiroshi Arima
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Hormone Replacement ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Hormone Deficiency ◽  
Adrenal Crisis ◽  
Mouse Escs

Abstract The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a three-dimensional culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in three-dimensional cultures of mouse ESCs. The ESCs were found to differentiate into both non-neural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the two tissues appear to be critically important for in vitro induction of a Rathke's pouch-like developing embryo. Various endocrine cells were differentiated from non-neural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.

Pluripotent Stem Cells Induced from Mouse Somatic Cells by Small-Molecule Compounds

Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 651-654 ◽  
Author(s):  
Pingping Hou ◽  
Yanqin Li ◽  
Xu Zhang ◽  
Chun Liu ◽  
Jingyang Guan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Genetic Manipulation ◽  
Expression Profiles ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Gene Expression Profiles ◽  
Clinical Applications

Pluripotent stem cells can be induced from somatic cells, providing an unlimited cell resource, with potential for studying disease and use in regenerative medicine. However, genetic manipulation and technically challenging strategies such as nuclear transfer used in reprogramming limit their clinical applications. Here, we show that pluripotent stem cells can be generated from mouse somatic cells at a frequency up to 0.2% using a combination of seven small-molecule compounds. The chemically induced pluripotent stem cells resemble embryonic stem cells in terms of their gene expression profiles, epigenetic status, and potential for differentiation and germline transmission. By using small molecules, exogenous “master genes” are dispensable for cell fate reprogramming. This chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.

Hepatic differentiation of pluripotent stem cells

2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Komal Loya ◽  
Reto Eggenschwiler ◽  
Kinarm Ko ◽  
Malte Sgodda ◽  
Francoise André ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Ethical Issues ◽  
Es Cells ◽  
Embryonic Stem ◽  
Hepatic Differentiation ◽  
Alternative Source ◽  
Organ Specific

Abstract In regenerative medicine pluripotent stem cells are considered to be a valuable self-renewing source for therapeutic cell transplantations, given that a functional organ-specific phenotype can be acquired by in vitro differentiation protocols. Furthermore, derivatives of pluripotent stem cells that mimic fetal progenitor stages could serve as an important tool to analyze organ development with in vitro approaches. Because of ethical issues regarding the generation of human embryonic stem (ES) cells, other sources for pluripotent stem cells are intensively studied. Like in less developed vertebrates, pluripotent stem cells can be generated from the female germline even in mammals, via parthenogenetic activation of oocytes. Recently, testis-derived pluripotent stem cells were derived from the male germline. Therefore, we compared two different hepatic differentiation approaches and analyzed the generation of definitive endoderm progenitor cells and their further maturation into a hepatic phenotype using murine parthenogenetic ES cells, germline-derived pluripotent stem cells, and ES cells. Applying quantitative RT-PCR, both germline-derived pluripotent cell lines show similar differentiation capabilities as normal murine ES cells and can be considered an alternative source for pluripotent stem cells in regenerative medicine.

Reprogramming of Somatic Cells After Fusion With Induced Pluripotent Stem Cells and Nuclear Transfer Embryonic Stem Cells

2010 ◽  
Vol 19 (2) ◽  
pp. 239-246 ◽  
Author(s):  
Huseyin Sumer ◽  
Karen L. Jones ◽  
Jun Liu ◽  
Corey Heffernan ◽  
Pollyanna A. Tat ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Nuclear Transfer ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Induced Pluripotent

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
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Somatic Cell ◽  
Pluripotent Stem Cells ◽  
Nuclear Transfer ◽  
Es Cells ◽  
Embryonic Stem ◽  
Therapeutic Cloning ◽  
Induced Pluripotent

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.

scholarly journals Experimental Limitations Using Reprogrammed Cells for Hematopoietic Differentiation

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Seiler ◽  
Motokazu Tsuneto ◽  
Fritz Melchers
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Clinical Settings ◽  
Hematopoietic Differentiation ◽  
Hematopoietic Stem ◽  
Induced Pluripotent

We review here our experiences with thein vitroreprogramming of somatic cells to induced pluripotent stem cells (iPSC) and subsequentin vitrodevelopment of hematopoietic cells from these iPSC and from embryonic stem cells (ESC). While, in principle, thein vitroreprogramming and subsequent differentiation can generate hematopoietic cell from any somatic cells, it is evident that many of the steps in this process need to be significantly improved before it can be applied to human cells and used in clinical settings of hematopoietic stem cell (HSC) transplantations.

Evidence That Human Very Small Embryonic-Like Stem Cells (VSELs) Are Mobilized by G-CSF Into Peripheral Blood: A Novel Strategy to Obtain Human Pluripotent Stem Cells for Regenerative Medicine.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1474-1474
Author(s):  
Satish Medicetty ◽  
Mariusz Z Ratajczak ◽  
Magdalena J Kucia ◽  
Ewa K. Zuba-Surma ◽  
Izabela Klich ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Peripheral Blood ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Employment Equity ◽  
Hematopoietic Stem ◽  
Equity Ownership ◽  
Novel Strategy

Abstract Abstract 1474 Poster Board I-497 We previously demonstrated that human cord blood contains a population of small (smaller in size than erythrocytes) CXCR4+CD133+CD34+SSEA-4+Oct-4+lin−CD45− cells (Leukemia 2007:21;297-303) and that these cells are mobilized into peripheral blood during tissue organ damage as seen for example in heart infarct (J. Am. Coll. Cardiol., 2009:53;1-9.) or stroke (Stroke. 2009:40;1237.). Similar cells were also reported in murine organs, and more importantly we described that these cells may differentiate in vitro into cells from all three germ layers (Leukemia 2006:20;857–869). To explore the possibility that human VSELs could become a source of pluripotent stem cells in regenerative medicine, our goal was to develop an efficient strategy to isolate these cells from adult patients. To test if VSELs similarly to their murine counterparts could be mobilized into peripheral blood after granulocyte colony stimulating factor (G-CSF) injection (Stem Cells 2008:26;2083-2092), we enrolled a group of young healthy donors who were mobilized for two consecutive days using G-CSF (480 μg/day subcutaneously). On the third day nucleated cells (TNC) were collected by apheresis. We evaluated number of VSELs in peripheral blood (PB) samples before and after G-CSF mobilization as well as the final number in the apheresis product. At least 1 million of TNC were acquired and analyzed by FACS Diva software. Three different fractions of non-hematopoietic stem cells enriched for VSELs (Lin−/CD45−/CD133+, Lin−/CD45−/CD34+, Lin−/CD45−/CXCR4+) as well as their CD45 positive hematopoietic counterparts were analyzed. The absolute numbers of cells from each population, contained in 1 μL of sample, were computed based on percent content of each population and TNC count for each individual sample. Results show that after G-CSF mobilization, human peripheral blood contains a population of lin− CD45− mononuclear cells that express CXCR4, CD34 and CD133 antigens. These lin− CD45− CXCR4+ CD133+ CD34+ cells are highly enriched for mRNA for intra-nuclear pluripotent embryonic transcription factors such as Oct-4, Sox2 and Nanog. More importantly we found that Oct-4 was expressed in nuclei of mobilized VSELs and that these cells also express the cell surface marker SSEA-4, the early embryonic glycolipid antigen commonly used as a marker for undifferentiated pluripotent human embryonic stem cells. We observed that these adult peripheral blood-derived VSELs are slightly larger than their counterparts identified in adult murine bone marrow, but are still very small. In addition, they also possess large nuclei containing embryonic-type unorganized euchromatin. Before G-CSF mobilization only very few VSELs were detectable in peripheral blood, whereas following G-CSF induced mobilization there was a very significant increase with in excess of 106 VSELs present in the apheresis product representing less than 0.01% of TNC. We postulate that while VSELs are relatively rare cells, they are mobilized into peripheral blood and that G-CSF induced mobilization could become a novel strategy to obtain human pluripotent stem cells for regenerative medicine. Disclosures: Medicetty: NeoStem Inc: Employment, Equity Ownership. Marasco: NeoStem Inc: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Rodgerson: NeoStem Inc: Employment, Equity Ownership.

scholarly journals Mitochondrial Dynamics: In Cell Reprogramming as It Is in Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Javier Prieto ◽  
Josema Torres
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Cellular Transformation ◽  
Cell Reprogramming ◽  
Mitochondrial Morphology ◽  
Pluripotent Cells

Somatic cells can be reprogrammed into a pluripotent cellular state similar to that of embryonic stem cells. Given the significant physiological differences between the somatic and pluripotent cells, cell reprogramming is associated with a profound reorganization of the somatic phenotype at all levels. The remodeling of mitochondrial morphology is one of these dramatic changes that somatic cells have to undertake during cell reprogramming. Somatic cells transform their tubular and interconnected mitochondrial network to the fragmented and isolated organelles found in pluripotent stem cells early during cell reprogramming. Accordingly, mitochondrial fission, the process whereby the mitochondria divide, plays an important role in the cell reprogramming process. Here, we present an overview of the importance of mitochondrial fission in both cell reprogramming and cellular transformation.

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