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

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.

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

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa188 ◽

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.

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5. Tissue-specific stem cells

10.1093/actrade/9780198869290.003.0005 ◽

2021 ◽

pp. 75-89

Author(s):

Jonathan Slack

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Es Cells ◽

Embryonic Stem ◽

Molecular Characteristics ◽

Cell Surface Molecules ◽

Tissue Specific ◽

Surface Molecules ◽

Induced Pluripotent ◽

Tissue Specific Stem Cells

‘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.

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

Stem Cell Research & Therapy ◽

10.1186/s13287-020-01916-z ◽

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.

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Hepatic differentiation of pluripotent stem cells

Biological Chemistry ◽

10.1515/bc.2009.120 ◽

2009 ◽

Vol 390 (10) ◽

Cited By ~ 15

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.

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Experimental Limitations Using Reprogrammed Cells for Hematopoietic Differentiation

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/895086 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 3

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.

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Differentiation of Human Pluripotent Stem Cells into Mesodermal and Ectodermal Derivatives Is Independent of the Type of Isogenic Reprogrammed Somatic Cells

Acta Naturae ◽

10.32607/20758251-2017-9-1-68-74 ◽

2017 ◽

Vol 9 (1) ◽

pp. 68-74 ◽

Cited By ~ 2

Author(s):

E. S. Philonenko ◽

M. V. Shutova ◽

Е. А. Khomyakova ◽

Е. М. Vassina ◽

О. S. Lebedeva ◽

...

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Somatic Cells ◽

Embryonic Stem ◽

Scientific Application ◽

Bottleneck Effect ◽

Genetic Manipulations ◽

Induced Pluripotent ◽

Selection Of

Induced pluripotent stem cells (iPSCs) have the capacity to unlimitedly proliferate and differentiate into all types of somatic cells. This capacity makes them a valuable source of cells for research and clinical use. However, the type of cells to be reprogrammed, the selection of clones, and the various genetic manipulations during reprogramming may have an impact both on the properties of iPSCs and their differentiated derivatives. To assess this influence, we used isogenic lines of iPSCs obtained by reprogramming of three types of somatic cells differentiated from human embryonic stem cells. We showed that technical manipulations in vitro, such as cell sorting and selection of clones, did not lead to the bottleneck effect, and that isogenic iPSCs derived from different types of somatic cells did not differ in their ability to differentiate into the hematopoietic and neural directions. Thus, the type of somatic cells used for the generation of fully reprogrammed iPSCs is not important for the practical and scientific application of iPSCs.

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Induction of meiosis by embryonic gonadal somatic cells differentiated from pluripotent stem cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02672-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Haiying Wang ◽

Linlin Liu ◽

Chang Liu ◽

Lingling Wang ◽

Jiyu Chen ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Germ Cell ◽

Small Molecules ◽

Somatic Cell ◽

Pluripotent Stem Cells ◽

Primordial Germ Cell ◽

Somatic Cells ◽

Embryonic Stem

Abstract Background Depletion of oocytes leads to ovarian aging-associated infertility, endocrine disruption and related diseases. Excitingly, unlimited oocytes can be generated by differentiation of primordial germ cell like cells (PGCLCs) from pluripotent stem cells. Nevertheless, development of oocytes and follicles from PGCLCs relies on developmentally matched gonadal somatic cells, only available from E12.5 embryos in mice. It is therefore imperative to achieve an in vitro source of E12.5 gonadal somatic cells. Methods We explored to identify small molecules, which can induce female embryonic stem cells (ESCs) into gonadal somatic cell like cells. Results Using RNA-sequencing, we identified signaling pathways highly upregulated in E12.5_gonadal somatic cells (E12.5_GSCs). Through searching for the activators of these pathways, we identified small-molecule compounds Vitamin C (Vc) and AM580 in combination (V580) for inducing differentiation of female embryonic stem cells (ESCs) into E12.5_GSC-like cells (E12.5_GSCLCs). After V580 treatment for 6 days and sorted by a surface marker CD63, the cell population yielded a transcriptome profile similar to that of E12.5_GSCs, which promoted meiosis progression and folliculogenesis of primordial germ cells. This approach will contribute to the study of germ cell and follicle development and oocyte production and have implications in potentially treating female infertility. Conclusion ESCs can be induced into embryonic gonadal somatic cell like cells by small molecules.

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Resetting Human Naïve Pluripotency

Genetics & Epigenetics ◽

10.4137/geg.s38093 ◽

2016 ◽

Vol 8 ◽

pp. GEG.S38093 ◽

Cited By ~ 5

Author(s):

Jifang Xiao ◽

Daniel H. Mai ◽

Liangqi Xie

Keyword(s):

Stem Cells ◽

Regenerative Medicine ◽

Pluripotent Stem Cells ◽

Inner Cell Mass ◽

Cell Mass ◽

Embryonic Stem ◽

Human Escs ◽

Pluripotent State ◽

Primed State

The rodent naive pluripotent state is believed to represent the preimplantation inner cell mass state of the developing blastocyst and can derive self-renewing pluripotent embryonic stem cells (ESCs) in vitro. Nevertheless, human ESCs exhibit epigenetic, metabolic, and transcriptomic characteristics more akin to primed pluripotent stem cells (PSCs) derived from the postimplantation epiblast. Understanding the genetic and epigenetic mechanisms that constrain human ESCs in the primed state is crucial for the human naive pluripotent state resetting and numerous applications in regenerative medicine. In this review, we begin by defining the naive and primed states in the murine model and compare the epigenetic characteristics of those states to the human PSCs. We also examine the various reprogramming schemes to derive the human naive pluripotent state. Finally, we discuss future perspectives of studying and deriving the human naive PSCs in the context of cellular engineering and regenerative medicine.

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

10.5772/intechopen.95070 ◽

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.

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Prospects for the use of the achievements of regenerative medicine in otorhinolaryngology

Polski Przegląd Otorynolaryngologiczny ◽

10.5604/01.3001.0009.7979 ◽

2017 ◽

Vol 6 (1) ◽

pp. 1-7

Author(s):

Andrzej K. Ciechanowicz

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Regenerative Medicine ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Bone Marrow Cells ◽

Embryonic Stem ◽

Promising Alternative ◽

Induced Pluripotent

Regenerative medicine is focusing on searching for stem cells, which can be efficiently and safely used for regeneration of damaged tissues and organs. Pluripotent stem cells would be ideal for this purpose. It is because they have the ability to differentiate into cells of all three germ layers (ecto-, meso- and endoderm). One of the sources of their isolation are embryos. For many years, they are made unsuccessful attempts to use of very controversial embryonic stem cells that are isolated from embryos. So strong ethical controversy forced scientists to look for other, undoubted ethically, sources of pluripotent stem cells. Induced pluripotent stem cells are proposed, as a more promising alternative to cells isolated from embryos. Unfortunately, both embryonic stem cells and induced pluripotent stem cells tend to genetic instability leading to the formation of teratomas. In parallel studies scientists try to use of stem cells isolated from adult tissues (e.g. bone marrow cells or adipose tissue) in the regeneration of parenchymal organs. Unfortunately, there is no convincing evidence for most of these cells that can regenerate damaged parenchymal organs. Regenerative medicine more frequently is employed in the otorhinolaryngological therapies. More and more researchers’ efforts are put into the development of an effective method of stimulation (in vitro) of pluripotent stem cells isolated from adult tissue for differentiation of the renewable progenitor stem cells which can keep their potential after transplantation into the recipient (e.g. in the treatment of imbalances or hearing loss). Moreover, there are promising methods for employing of the stem cells potential in tissue engineering as they are more effectively introduced as a clinical therapies.

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