Patient-Specific Pluripotent Stem Cells for Hematologic Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-40-SCI-40
Author(s):  
George Q. Daley
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Nuclear Transfer ◽  
Es Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Patient Specific ◽  
Direct Reprogramming ◽  
Disease Specific

Abstract Abstract SCI-40 Pluripotent stem cells can be isolated from embryos (embryonic stem cells; ES cells) or generated by direct reprogramming of somatic cells (induced pluripotent stem cells; iPS cells). Both types can be differentiated into a multitude of cell lineages to serve disease research and cell replacement therapies. Additionally, genetically matched pluripotent stem cells generated via nuclear transfer (ntES cells), parthenogenesis (pES cells), or direct reprogramming (iPS cells) are a possible source of histocompatible cells and tissues for transplantation. We have used customized ntES cells to repair genetic immunodeficiency in mice (Rideout et al., Cell 2002); however, generation of ES cells by nuclear transfer remains inefficient, and to date has not been achieved with human cells. We have also generated ES cells with defined histocompatibility loci by direct parthenogenetic activation of the unfertilized oocyte (Kim et al., Science 2007). Compared to ES cell lines from fertilized embryos, pES cells display comparable in vitro hematopoietic activity, but appear compromised in repopulating hematopoiesis in irradiated adult mouse recipients. We are currently comparing the performance of ntES, pES, and iPS cells in murine models of thalassemia. We have generated human iPS cells by direct reprogramming of human somatic cells with OCT4, SOX2, MYC, and KLF4 (Park et al., Nature 2008), and have generated disease-specific iPS cells from patients with a number of hematologic conditions (Park et al., Cell 2008; Agarwal et al., submitted). Applications of disease-specific cells for investigating the mechanisms of reprogramming and for probing aspects of human bone marrow disorders will be discussed. Disclosures Daley: iPierian: Consultancy, Equity Ownership; Epizyme: Consultancy; Solasia: Consultancy; MPM Capital: Consultancy.

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.

294 PRODUCTION AND CHARACTERIZATION OF PUTATIVE NUCLEAR TRANSFER EMBRYONIC STEM CELLS DERIVED FROM HANDMADE CLONED EMBRYOS USING EMBRYONIC STEM CELLS, LYMPHOCYTES, AND ADULT FIBROBLAST CELLS AS DONOR CELLS IN GOAT

2011 ◽  
Vol 23 (1) ◽  
pp. 244
Author(s):  
R. Dutta ◽  
D. Malakar ◽  
K. Khate ◽  
J. Akshay
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Nuclear Transfer ◽  
Es Cells ◽  
Embryonic Stem ◽  
Donor Cell ◽  
Patient Specific ◽  
Fibroblast Cells ◽  
Donor Cells ◽  
Adult Fibroblasts

The handmade cloning technique has been a relatively recent addition in the field of nuclear transfer. In the present study, attempts were made to efficiently derive stem cells from handmade cloned (HMC) embryos in goat using adult fibroblast cells, embryonic stem (ES) cells, and lymphocytes as donor cells, and to characterise the derived putative nuclear transfer ES (ntES) cells for their stemness. Efficiency of the donor cells for nuclear transfer was also compared, and an overall cleavage and morula formation rates of 62.44 ± 3.9% and 35.30 ± 3.86%, 75.45 ± 3.92% and 45.84 ± 3.86%, and 56.38 ± 3.92% and 29.09 ± 3.86% were obtained from adult fibroblasts, ES cells, and lymphocytes, respectively. A significant difference was found between ES cells and the other 2 donor cells in terms of cleavage and morula formation. However, no such difference existed between fibroblasts and lymphocyte donor cells. Stem cell colonies were successfully derived from HMC embryos obtained from all 3 different donor cells. The rate of primary colony formation was 61.66 ± 4.62% for fibroblast-donor-cell-derived embryos. This rate was 59.91 ± 4.62% for ES-donor-cell-derived embryos and 62.49 ± 4.62% for lymphocyte-donor-cell-derived embryos. The putative ntES colonies were positively characterised for TRA-1-60, TRA-1-81, SSEA-1, SSEA-4, OCT-4, SOX-2, and Nanog by immunocytochemistry and RT-PCR. Results indicated that ES cells had better efficiency as donor cells in cloned embryo production than did adult fibroblasts and lymphocytes. The finding also suggested that terminally differentiated cell-like lymphocytes can also be reprogrammed. Moreover, there was no difference between the different donor-cell-derived HMC embryos in terms of ntES cell derivation. The study has established an efficient protocol for putative ntES cell derivation from HMC embryos. This could be of substantial significance because patient-specific ntES cells have proven therapeutic significance. The authors acknowledge N.D.R.I for the financial and infrastructural assistance.

Advances and applications of induced pluripotent stem cells

2012 ◽  
Vol 90 (3) ◽  
pp. 317-325 ◽  
Author(s):  
Stefano Pietronave ◽  
Maria Prat
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Ips Cells ◽  
Emerging Technology ◽  
Patient Specific ◽  
Direct Reprogramming ◽  
Pluripotent Cells ◽  
New Methods ◽  
Induced Pluripotent

Direct reprogramming of somatic cells into pluripotent cells is an emerging technology for creating patient-specific cells, and potentially opens new scenarios in medical and pharmacological fields. From the discovery of Shinya Yamanaka, who first obtained pluripotent cells from fibroblasts by retrovirus-derived ectopic expression of defined embryonic transcription factors, new methods have been developed to generate safe induced pluripotent stem (iPS) cells without genomic manipulations. This review will focus on the recent advances in iPS technology and their application in pharmacology and medicine.

Abstract 364: Valproic Acid Induced Reprogramming of Adult Somatic Cells for Cardiac Differentiation

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Zeeshan Pasha ◽  
Muhammad Ashraf
Keyword(s):  
Stem Cells ◽  
Valproic Acid ◽  
Embryonic Stem Cells ◽  
Small Molecule ◽  
Es Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Embryoid Bodies ◽  
Endogenous Expression

Aims: Owing to the ethical concerns for use of embryonic stem cells (ESC), adult somatic cells are attractive stem cell sources for reprogramming to pluripotency. We report here non-viral approach for reprogramming of skeletal myoblasts (SM) using a small molecule. Methods and Results: SM purified from young male Oct3/4-GFP+ transgenic mouse were treated for 5 days with valproic acid (VPA), a histone deacetylase (HDAC) inhibitor. Three weeks later, GFP+ colonies of SM derived iPSC (Sk-iPS) resembling with mouse embryonic stem cells were observed and propagated in vitro. SiPS were positive for alkaline phosphatase, had normal karyotype, expressed SSEA1, and induced teratomas in nude mice containing tissue comprising all three germ layers. RT PCR analysis showed that Sk-iPS cells expressed Oct4, Sox2, KLF4, c-Myc, Nanog and ESC specific pluripotency genes. HDAC1 activity was significantly reduced in Sk-iPs generated with valproic acid treatment as compared to ES cells. Sk-iPS derived embryoid bodies (EBs) yielded spontaneously contracting cardiomyocytes with morphological, molecular, and ultrastructural features of developing cardiomyocytes. These cells were also positive for early and late cardiac markers such as myosin heavy chain, Gata4, Mef-2c and Nkx2.5, Connexin-43 (P<0.01vs native SM). Micro RNA (miR) profiling showed abolition of let-7 family in Sk-iPS whereas ESC specific family of miR-290-295 was upregulated which indicated that Sk-iPS possessed miR profile similar to ESC. However muscle specific miRNAs (miR -133, -206) were identified in Sk-iPS cells as compared to ES cells indicating that the Sk-iPS retained the epigenetic memory of myogenic origin. Conclusions: We conclude that SM with endogenous expression of Sox2, KLF4, and cMyc are suitable candidates to generate iPS cells without viral vectors using a single small molecule.

scholarly journals The Promise of Human Induced Pluripotent Stem Cells in Dental Research

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Thekkeparambil Chandrabose Srijaya ◽  
Padmaja Jayaprasad Pradeep ◽  
Rosnah Binti Zain ◽  
Sabri Musa ◽  
Noor Hayaty Abu Kasim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Patient Specific ◽  
Dental Research ◽  
Cell Based Therapy ◽  
Induced Pluripotent ◽  
Disease Specific

Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC linesin vitrofrom patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.

scholarly journals Designer blood: creating hematopoietic lineages from embryonic stem cells

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1265-1275 ◽  
Author(s):  
Abby L. Olsen ◽  
David L. Stachura ◽  
Mitchell J. Weiss
Keyword(s):  
Stem Cells ◽  
Es Cells ◽  
Embryonic Stem ◽  
Basic Research ◽  
Cell Types ◽  
Patient Specific ◽  
Es Cell ◽  
Blood Disorders ◽  
Hematopoietic Stem

Embryonic stem (ES) cells exhibit the remarkable capacity to become virtually any differentiated tissue upon appropriate manipulation in culture, a property that has been beneficial for studies of hematopoiesis. Until recently, the majority of this work used murine ES cells for basic research to elucidate fundamental properties of blood-cell development and establish methods to derive specific mature lineages. Now, the advent of human ES cells sets the stage for more applied pursuits to generate transplantable cells for treating blood disorders. Current efforts are directed toward adapting in vitro hematopoietic differentiation methods developed for murine ES cells to human lines, identifying the key interspecies differences in biologic properties of ES cells, and generating ES cell-derived hematopoietic stem cells that are competent to repopulate adult hosts. The ultimate medical goal is to create patient-specific and generic ES cell lines that can be expanded in vitro, genetically altered, and differentiated into cell types that can be used to treat hematopoietic diseases.

5. Tissue-specific stem cells

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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