Potential benefits of cell cloning for human medicine

The successful cloning of a mammal from an adult somatic cell nucleus opens new avenues for major advances in reproductive medicine, biotechnology and cellular-based transplantation therapies for degenerative diseases. At the same time, this breakthrough has generated much heated discussion concerning the ethics of cloning. Twinning is a form of cloning, and there are instances in clinical assisted reproduction in which the deliberate formation of twins by embryo dissection would seem ethically acceptable. Nuclear transfer technology might facilitate the derivation of human embryonic stem cells, capable of differentiation into a wide variety of somatic cell lineages. Directed differentiation of human embryonic stem cells into specific cell types in vitro could provide a universal source of cells for transplantation therapy. The potential benefits of therapeutics based on cloning technologies are considerable, and hasty legislation to ban all such procedures could block progress in critical arenas of biomedical research

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Differential resistance of human embryonic stem cells and somatic cell types to hydrogen peroxide-induced genotoxicity may be dependent on innate basal intracellular ROS levels

Folia Histochemica et Cytobiologica ◽

10.5603/fhc.a2015.0016 ◽

2015 ◽

Vol 53 (2) ◽

pp. 169-174 ◽

Cited By ~ 5

Author(s):

Kumar Jayaseelan Vinoth ◽

Jayapal Manikandan ◽

Swaminathan Sethu ◽

Lakshmidevi Balakrishnan ◽

Alexis Heng ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Somatic Cell ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Differential Resistance ◽

Cell Types ◽

Intracellular Ros

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The derivation and potential use of human embryonic stem cells

Reproduction Fertility and Development ◽

10.1071/rd01101 ◽

2001 ◽

Vol 13 (8) ◽

pp. 523 ◽

Cited By ~ 28

Author(s):

Alan O. Trounson

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Regenerative Medicine ◽

Human Embryonic Stem Cells ◽

High Efficiency ◽

Es Cells ◽

Cell Mass ◽

Embryonic Stem ◽

Cell Types ◽

Specific Cell

Human embryonic stem cells lines can be derived from human blastocysts at high efficiency (>50%) by immunosurgical isolation of the inner cell mass and culture on embryonic fibroblast cell lines. These cells will spontaneously differentiate into all the primary embryonic lineages in vitro and in vivo, but they are unable to form an integrated embryo or body plan by themselves or when combined with trophectoderm cells. They may be directed into a number of specific cell types and this enrichment process requires specific growth factors, cell-surface molecules, matrix molecules and secreted products of other cell types. Embryonic stem (ES) cells are immortal and represent a major potential for cell therapies for regenerative medicine. Their use in transplantation may depend on the formation of a large bank of suitable human leucocyte antigen (HLA) types or the genetic erasure of their HLA expression. Successful transplantation may also require induction of tolerance in recipients and ongoing immune suppression. Although it is possible to customize ES cells by therapeutic cloning or cytoplasmic transfer, it would appear unlikely that these strategies will be used extensively for producing ES cells compatible for transplantation. Embryonic stem cell research may deliver a new pathway for regenerative medicine.

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The Production and Directed Differentiation of Human Embryonic Stem Cells

Endocrine Reviews ◽

10.1210/er.2005-0016 ◽

2006 ◽

Vol 27 (2) ◽

pp. 208-219 ◽

Cited By ~ 155

Author(s):

Alan Trounson

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Regenerative Medicine ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Cell Types ◽

Embryoid Bodies ◽

Directed Differentiation ◽

Hesc Lines

Human embryonic stem cells (hESCs) are being rapidly produced from chromosomally euploid, aneuploid, and mutant human embryos that are available from in vitro fertilization clinics treating patients for infertility or preimplantation genetic diagnosis. These hESC lines are an important resource for functional genomics, drug screening, and, perhaps eventually, cell and gene therapy. The methods for deriving hESCs are well established and repeatable and are relatively successful with a ratio of 1:10 to 1:2 new hESC lines produced from 4- to 8-d-old morula and blastocysts and from isolated inner cell mass cell clusters of human blastocysts. The hESCs can be formed and maintained on human somatic cells in humanized serum-free culture conditions and for several passages in cell-free culture systems. The hESCs can be transfected with DNA constructs. Their gene expression profiles are being described and immunological characteristics determined. They may be grown indefinitely in vitro while maintaining their original karyotype and epigenetic status, but this needs to be confirmed from time to time in long-term cultures. hESCs spontaneously differentiate in the absence of the appropriate cell feeder layer, when overgrown in culture and when isolated from the ESC colony. All three major embryonic lineages are produced in differentiating flat attachment cultures and unattached embryoid bodies. Cell progenitors of interest can be identified by markers, expression of reporter genes, and characteristic morphology, and the cells thereafter enriched for progenitor types and further culture to more mature cell types. Directed differentiation systems are well developed for ectodermal pathways that result in neural and glial cells and the mesendodermal pathway for cardiac muscle cells and many other cell types including hematopoietic progenitors and endothelial cells. Directed differentiation into endoderm has been more difficult to achieve, perhaps because of the lack of markers of early progenitors in this lineage. There are reports of enriched cultures of keratinocytes, pigmented retinal epithelium, neural crest cells and motor neurons, hepatic progenitors, and cells that have some markers of gut tissue and pancreatic islet-like cells. The prospects for use of hESC derivatives in regenerative medicine are significant, and there is much optimism for their potential contributions to human regenerative medicine.

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Epithelial Cells Derived from Human Embryonic Stem Cells Display P16INK4ASenescence, Hypermotility, and Differentiation Properties Shared by Many P63+Somatic Cell Types

Stem Cells ◽

10.1002/stem.64 ◽

2009 ◽

Vol 27 (6) ◽

pp. 1388-1399 ◽

Cited By ~ 31

Author(s):

Sally Dabelsteen ◽

Paula Hercule ◽

Patricia Barron ◽

Meghan Rice ◽

Gregory Dorsainville ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Epithelial Cells ◽

Somatic Cell ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Cell Types

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Faculty Opinions recommendation of INS(GFP/w) human embryonic stem cells facilitate isolation of in vitro derived insulin-producing cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13984975.15442093 ◽

2012 ◽

Author(s):

Gordon Weir

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Insulin Producing Cells

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Faculty Opinions recommendation of CORTECON: a temporal transcriptome analysis of in vitro human cerebral cortex development from human embryonic stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718478232.793498745 ◽

2014 ◽

Author(s):

Vijay Tiwari ◽

Johannes Jung

Keyword(s):

Stem Cells ◽

Cerebral Cortex ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Transcriptome Analysis ◽

Embryonic Stem ◽

Human Cerebral Cortex ◽

Cerebral Cortex Development

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Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro

Tissue Engineering and Regenerative Medicine ◽

10.1007/s13770-021-00359-8 ◽

2021 ◽

Author(s):

Eun-Young Shin ◽

Seah Park ◽

Won Yun Choi ◽

Dong Ryul Lee

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Male Hypogonadism ◽

Testosterone Levels ◽

Sequence Of Events ◽

Short Period ◽

Molecular Compounds

Abstract Background: Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males. Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate in vitro. Therefore, there is a need for an alternative source of LCs. Methods: To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. Results: HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. Conclusion: We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.

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