scholarly journals Bioprinting Technology as a Legal Challenge: Determining the Model of Legal Regulation

Lex Russica ◽  
2019 ◽  
pp. 80-91
Author(s):  
D. E. Bogdanov
Keyword(s):  
Stem Cells ◽  
3D Printing ◽  
3D Models ◽  
Physical World ◽  
Legal Regulation ◽  
Material World ◽  
Human Organs ◽  
Differentiated Cells ◽  
The Creation ◽  
Induced Pluripotent

The technology of 3D printing creates serious challenges to the legal system that in its development is lagging behind scientific and technological progress. The development of 3D printing technology leads to the «digitalization» of objects of the material world when the boundaries between the physical world and the digital space are blurred. If 3D printing digitalizes objects of the material world, bioprinting digitalizes the human body. An individual tends to depend on the digital incarnation of his body or its individual organs in the corresponding electronic 3D models.Bioprinting is aimed at the formation of a new medical paradigm that will result in overcoming the deficiency of human organs and tissues in the field of transplantology. The discovery of the possibility of reprogramming differentiated cells and obtaining induced pluripotent stem cells eliminates the ethical and legal problem associated with the use of stem cells of the embryo. This should be taken into account in the development of a model of legal regulation of relations connected with the creation of bio-print human organs.Bioprint organs are synthetic organs, so the relations associated with their creation and implantation need independent legal regulation. Contemporary transplantology legislation and bans and prohibitions contained in it do not take into account the features of the creation of organs through 3D bioprinting. It is acceptable to commercialize relations in the field of bioprinting, to perform non-gratuitous transactions in this area, as well as to permit limited turnover of «bioprinting» organs subjecting them to the regulation applied to any other objects of civil law. Legislation on biomedical cellular products is also not able to regulate relations related to the creation and implantation of bio-printed human organs. Thus, the need arises to adopt a special legislative act aimed at regulating relations at all stages of the use of bioprinting technology.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

2021 ◽  
Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
3D Models ◽  
Induced Pluripotent

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

Regenerating Life

2020 ◽  
pp. 185-208
Author(s):  
John Parrington
Keyword(s):  
Stem Cells ◽  
Ethical Issues ◽  
Brain Size ◽  
Embryonic Stem ◽  
Cell Types ◽  
Structural Features ◽  
Human Organs ◽  
3D Matrix ◽  
Immortal Cells ◽  
Induced Pluripotent

Stem cells, which are ‘immortal’ cells that divide indefinitely and produce many different cell types, are central to how our body develops and maintains itself. Embryonic stem cells can give rise to all cell types in the body, and there has been lots of interest since their discovery in the 1980s in using such cells to generate new tissues or organs to replace diseased or faulty ones. More recently has come the discovery of induced pluripotent stem cells, which are normal skin cells taken from a person and genetically modified or tweaked chemically to give them stem cell properties. There is now hope that both of these types of stem cells might be used in ‘regenerative’ medicine, for instance in producing pancreatic cells that secrete insulin which could be used to treat diabetes. Perhaps the most remarkable breakthrough in recent years has been the discovery that stem cells introduced into a 3D matrix that is infused with chemicals that stimulate the development of particular cell types, can spontaneously form ‘organoids’, which have many of the cell types and even structural features of human organs such as hearts, kidneys, intestines, and even eyes and brains. Organoids make it possible to study how human organs develop but also this area of science raises many ethical issues. For instance, currently human brain organoids can only grow to the size of an embryonic brain, but if in the future they could be induced to grow to adult brain size, could they develop feelings and thoughts?

scholarly journals Mammalian genes induce partially reprogrammed pluripotent stem cells in non-mammalian vertebrate and invertebrate species

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ricardo Antonio Rosselló ◽  
Chun-Chun Chen ◽  
Rui Dai ◽  
Jason T Howard ◽  
Ute Hochgeschwender ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Mammalian Species ◽  
Embryonic Stem ◽  
Model Organisms ◽  
Differentiated Cells ◽  
Transcription Factor Genes ◽  
Induced Pluripotent

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.

scholarly journals Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells

2017 ◽  
Vol 21 (1) ◽  
pp. 144-148 ◽  
Author(s):  
Prajna Guha ◽  
John W. Morgan ◽  
Gustavo Mostoslavsky ◽  
Neil P. Rodrigues ◽  
Ashleigh S. Boyd
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Differentiated Cells ◽  
Induced Pluripotent

scholarly journals iPSC Bioprinting: Where are We at?

Materials ◽  
2019 ◽  
Vol 12 (15) ◽  
pp. 2453 ◽  
Author(s):  
Sara Romanazzo ◽  
Stephanie Nemec ◽  
Iman Roohani
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Specific Treatment ◽  
The Body ◽  
Patient Specific ◽  
Hepatic Tissue ◽  
Advantages And Disadvantages ◽  
Differentiated Cells ◽  
Ipsc Generation ◽  
Induced Pluripotent

Here, we present a concise review of current 3D bioprinting technologies applied to induced pluripotent stem cells (iPSC). iPSC have recently received a great deal of attention from the scientific and clinical communities for their unique properties, which include abundant adult cell sources, ability to indefinitely self-renew and differentiate into any tissue of the body. Bioprinting of iPSC and iPSC derived cells combined with natural or synthetic biomaterials to fabricate tissue mimicked constructs, has emerged as a technology that might revolutionize regenerative medicine and patient-specific treatment. This review covers the advantages and disadvantages of bioprinting techniques, influence of bioprinting parameters and printing condition on cell viability, and commonly used iPSC sources, and bioinks. A clear distinction is made for bioprinting techniques used for iPSC at their undifferentiated stage or when used as adult stem cells or terminally differentiated cells. This review presents state of the art data obtained from major searching engines, including Pubmed/MEDLINE, Google Scholar, and Scopus, concerning iPSC generation, undifferentiated iPSC, iPSC bioprinting, bioprinting techniques, cartilage, bone, heart, neural tissue, skin, and hepatic tissue cells derived from iPSC.

scholarly journals Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Tackla S. Winston ◽  
Kantaphon Suddhapas ◽  
Chenyan Wang ◽  
Rafael Ramos ◽  
Pranav Soman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Culture Conditions ◽  
Serum Free ◽  
Differentiated Cells ◽  
Induced Pluripotent

Combination of stem cell technology and 3D biofabrication approaches provides physiological similarity to in vivo tissues and the capability of repairing and regenerating damaged human tissues. Mesenchymal stem cells (MSCs) have been widely used for regenerative medicine applications because of their immunosuppressive properties and multipotent potentials. To obtain large amount of high-quality MSCs without patient donation and invasive procedures, we differentiated MSCs from human-induced pluripotent stem cells (hiPSC-MSCs) using serum-free E6 media supplemented with only one growth factor (bFGF) and two small molecules (SB431542 and CHIR99021). The differentiated cells showed a high expression of common MSC-specific surface markers (CD90, CD73, CD105, CD106, CD146, and CD166) and a high potency for osteogenic and chondrogenic differentiation. With these cells, we have been able to manufacture MSC tissue rings with high consistency and robustness in pluronic-coated reusable PDMS devices. The MSC tissue rings were characterized based on inner diameter and outer ring diameter and observed cell-type-dependent tissue contraction induced by cell-matrix interaction. Our approach of simplified hiPSC-MSC differentiation, modular fabrication procedure, and serum-free culture conditions has a great potential for scalable manufacturing of MSC tissue rings for different regenerative medicine applications.

Differentiation of human induced pluripotent stem cells into testosterone-producing Leydig-like cells

Endocrinology ◽  
2021 ◽  
Author(s):  
Takaki Ishida ◽  
Michiyo Koyanagi-Aoi ◽  
Daisuke Yamamiya ◽  
Atsushi Onishi ◽  
Katsuya Sato ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Leydig Cells ◽  
Late Onset ◽  
Testosterone Replacement Therapy ◽  
Promising Alternative ◽  
Differentiated Cells ◽  
Induced Pluripotent ◽  
Late Onset Hypogonadism

Abstract Late-onset hypogonadism (LOH) syndrome due to a partial lack of testosterone, which is mainly secreted by Leydig cells in the testes, decreases the quality of life of older men. Leydig cell transplantation is expected to be a promising alternative to conventional testosterone replacement therapy (TRT) for LOH syndrome. We herein report a simple and robust protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into Leydig-like cells by doxycycline-inducible overexpression of NR5A1 and treatment with a combination of 8-bromoadenosine-3’,5’-cyclic monophosphate (8-Br-cAMP) and forskolin. The differentiated cells expressed the steroidogenic enzyme genes STAR, CYP11A1, CYP17A1 and HSD3B2 and the specific markers of adult Leydig cells HSD17B3, INSL3 and LHCGR. Furthermore, we confirmed the secretion of functional testosterone from the cells into the culture supernatant by a testosterone-sensitive cell proliferation assay. These findings showed that the hiPSCs were able to be differentiated into Leydig-like cells, supporting the expectation that hiPSC-derived Leydig-like cells can be novel tools for treating LOH syndrome.

scholarly journals Differentiation of Human Embryonic Stem Cells and Human Induced Pluripotent Stem Cells into Steroid-Producing Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4336-4345 ◽  
Author(s):  
Takuhiro Sonoyama ◽  
Masakatsu Sone ◽  
Kyoko Honda ◽  
Daisuke Taura ◽  
Katsutoshi Kojima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regulatory Protein ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Steroidogenic Acute Regulatory Protein ◽  
Steroidogenic Factor 1 ◽  
Differentiated Cells ◽  
Steroidogenic Acute Regulatory ◽  
Induced Pluripotent ◽  
Mesodermal Lineage

Although there have been reports of the differentiation of mesenchymal stem cells and mouse embryonic stem (ES) cells into steroid-producing cells, the differentiation of human ES/induced pluripotent stem (iPS) cells into steroid-producing cells has not been reported. The purpose of our present study was to establish a method for inducing differentiation of human ES/iPS cells into steroid-producing cells. The first approach we tried was embryoid body formation and further culture on adherent plates. The resultant differentiated cells expressed mRNA encoding the steroidogenic enzymes steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, cytochrome P450-containing enzyme (CYP)-11A1, CYP17A1, and CYP19, and secreted progesterone was detected in the cell medium. However, expression of human chorionic gonadotropin was also detected, suggesting the differentiated cells were trophoblast like. We next tried a multistep approach. As a first step, human ES/iPS cells were induced to differentiate into the mesodermal lineage. After 7 d of differentiation induced by 6-bromoindirubin-3′-oxime (a glycogen synthase kinase-3β inhibitor), the human ES/iPS cells had differentiated into fetal liver kinase-1- and platelet derived growth factor receptor-α-expressing mesodermal lineage cells. As a second step, plasmid DNA encoding steroidogenic factor-1, a master regulator of steroidogenesis, was introduced into these mesodermal cells. The forced expression of steroidogenic factor-1 and subsequent addition of 8-bromoadenosine 3′,5′-cyclic monophosphate induced the mesodermal cells to differentiate into the steroidogenic cell lineage, and expression of CYP21A2 and CYP11B1, in addition to steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, CYP11A1, and CYP17A1, was detected. Moreover, secreted cortisol was detected in the medium, but human chorionic gonadotropin was not. These findings indicate that the steroid-producing cells obtained through the described multistep method are not trophoblast like; instead, they exhibit characteristics of adrenal cortical cells.

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