Human Skin Cells Reprogrammed Into Embryonic Stem Cells

Science News
Human Skin Cells Reprogrammed Into Embryonic Stem Cells
ScienceDaily (Feb. 12, 2008) — UCLA stem cell scientists have reprogrammed human skin cells into cells with the same unlimited properties as embryonic stem cells without using embryos or eggs.
Led by scientists Kathrin Plath and William Lowry, UCLA researchers used genetic alteration to turn back the clock on human skin cells and create cells that are nearly identical to human embryonic stem cells, which have the ability to become every cell type found in the human body. Four regulator genes were used to create the cells, called induced pluripotent stem cells or iPS cells.
The implications for disease treatment could be significant. Reprogramming adult stem cells into embryonic stem cells could generate a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine. A patient's skin cells, for example, could be reprogrammed into embryonic stem cells. Those embryonic stem cells could then be prodded into becoming various cells types -- beta islet cells to treat diabetes, hematopoetic cells to create a new blood supply for a leukemia patient, motor neuron cells to treat Parkinson's disease.
"Our reprogrammed human skin cells were virtually indistinguishable from human embryonic stem cells," said Plath, an assistant professor of biological chemistry, a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and lead author of the study. "Our findings are an important step towards manipulating differentiated human cells to generate an unlimited supply of patient specific pluripotent stem cells. We are very excited about the potential implications."
The UCLA study confirms the work first reported in late November of researcher Shinya Yamanaka at Kyoto University and James Thompson at the University of Wisconsin. The UCLA research appears Feb. 11, 2008, in an early online edition of the journal Proceedings of the National Academy of the Sciences. The UCLA work was completed at about the same time the Yamanaka and Thomson reports were published. Taken together, the studies demonstrate that human iPS cells can be easily created by different laboratories and are likely to mark a milestone in stem cell-based regenerative medicine, Plath said.
These new techniques to develop stem cells could potentially replace a controversial method used to reprogram cells, somatic cell nuclear transfer (SCNT), sometimes referred to as therapeutic cloning. To date, therapeutic cloning has not been successful in humans. However, top stem cell scientists worldwide stress that further research comparing these reprogrammed cells with stem cells derived from embryos, considered the gold standard, is necessary. Additionally, many technical problems, such as the use of viruses to deliver the four genes for reprogramming, need to be overcome to produce safe iPS cells that can be used in the clinic.
"Reprogramming normal human cells into cells with identical properties to those in embryonic stem cells without SCNT may have important therapeutic ramifications and provide us with another valuable method to develop human stem cell lines," said Lowry, an assistant professor of molecular, cell and developmental biology, a Broad Stem Cell Center researcher and first author of the study. "It is important to remember that our research does not eliminate the need for embryo-based human embryonic stem cell research, but rather provides another avenue of worthwhile investigation."
The combination of four genes used to reprogram the skin cells regulate expression of downstream genes and either activate or silence their expression. The reprogrammed cells were not just functionally identical to embryonic stem cells. They also had identical biological structure, expressed the same genes and could be coaxed into giving rise to the same cell types as human embryonic stem cells.
The UCLA research team included four young scientists recruited to UCLA's new stem cell center in the wake of the passage of Proposition 71 in 2004, which created $3 billion in funding for embryonic stem cell research. The scientists were drawn to UCLA in part because of California's stem cell research friendly atmosphere and the funding opportunities created by Proposition 71. In addition to Plath and Lowry, the team included Amander Clarke, an assistant professor of molecular, cell and developmental biology, and April Pyle, an assistant professor of microbiology, immunology and molecular genetics.
The creation of the human iPS cells is an extension of Plath's work on mouse stem cell reprogramming. Plath headed up one of three research teams that were able to successfully reprogram mouse skin cells into mouse embryonic stem cells. That work appeared in the June 2007 issue of the journal Cell Stem Cell.
Adapted from materials provided by University of California - Los Angeles.

Frequently asked questions about stem cells

Frequently Asked Questions (FAQs)--from NIH.GOV
Basic Questions
What are human embryonic stem cells?
What classes of stem cells are there?
Where do stem cells come from?
Why do scientists want to use stem cell lines?
Healthcare Questions
Why are doctors and scientists so excited about human embryonic stem cells?
Have human embryonic stem cells been used successfully to treat any human diseases yet?
What will be the best type of stem cell to use for therapy?
I have Parkinson's Disease. Is there a clinical trial that I can participate in that uses stem cell as therapy?
Where can I donate umbilical cord stem cells?
Research and Policy Questions
Which research is best to pursue?
Why not use adult stem cells instead of using human embryonic stem cells in research?
What are the NIH Guidelines on the utilization of stem cells derived from human fetal tissue (embryonic germ cells)?
May individual states pass laws to permit human embryonic stem cell research?
Where can I find information about patents obtained for stem cells?
Cell Line Availability and the Registry
I am a scientist funded by the NIH. How many cell lines are available to me, and how do I get them?
I'm interested in purchasing more than one cell line from the NIH Stem Cell Registry. What is known about the status of the cell lines and their availability?
Who owns the cells?
When does NIH anticipate that more stem cells lines will become available?
What policies govern use of stem cell lines from WiCell Research Institute?
Funding Questions
Does NIH fund embryonic stem cell research?
Are there any areas of research involving human pluripotent stem cells that are ineligible for NIH funding?
Can a scientist supported by federal funds conduct research with stem cell lines that are not listed on the NIH Human Embryonic Stem Cell Registry?
What if a scientist is conducting research with both federally fundable and non-federally fundable human embryonic stem cells?
Who is responsible for setting the policy to allow federal money to be used for human embryonic stem cell research?
I am a university research administrator. One of our NIH-funded investigators would like to use a cell line that was created after August 9th, 2001, and it is not eligible for research using federal funds. What should I tell the investigator who wants to work with these cells in his laboratory?
I am an investigator who receives NIH funding, and I am planning to derive new human embryonic stem cell lines. Can I conduct the derivations in my laboratory, or do I need to find a non-university funded laboratory to do this work?
Can you explain what accounting principles are necessary to demonstrate that unallowable charges are not being absorbed by NIH funded research, e.g., indirect costs?
May I use data produced from studies of non-approved human embryonic stem cell (hESC) lines under an NIH-supported project?
Can a DNA clone or plasmid or other research resource originally generated with NIH funds be used in the study of non-approved cell lines?
May a common resource area be created that allows scientists working on unapproved lines and other scientists working on approved lines to use some of the same equipment and common resources (pipettes, glassware, etc.)?

Recent Progresses in Stem Cell Multiponent Differentiation

Ungrin MD, Joshi C, Nica A, Bauwens C, Zandstra PW.

Reproducible, Ultra High-Throughput Formation of Multicellular Organization from Single Cell Suspension-Derived Human Embryonic Stem Cell Aggregates.
PLoS ONE. 2008 Feb 13;3(2):e1565.

Dalby MJ, Andar A, Nag A, Affrossman S, Tare R, McFarlane S, Oreffo RO.

Genomic expression of mesenchymal stem cells to altered nanoscale topographies.
J R Soc Interface. 2008 Feb 12; [Epub ahead of print]

Xu Y, Liu Z, Liu L, Zhao C, Xiong F, Zhou C, Li Y, Shan Y, Peng F, Zhang C.

Neurospheres from rat adipose-derived stem cells could be induced into functional Schwann cell-like cells in vitro.
BMC Neurosci. 2008 Feb 12;9(1):21 [Epub ahead of print]

Arnes JB, Collett K, Akslen LA.

Independent prognostic value of the basal-like phenotype of breast cancer and associations with EGFR and candidate stem cell marker BMI-1.
Histopathology. 2008 Feb;52(3):370-80.

Fan H, Zhang C, Li J, Bi L, Qin L, Wu H, Hu Y.

Gelatin Microspheres Containing TGF-beta3 Enhance the Chondrogenesis of Mesenchymal Stem Cells in Modified Pellet Culture.
Biomacromolecules. 2008 Feb 13; [Epub ahead of print]

[Germ track and stem cells in higher plants]
Tsitol Genet. 2007 Sep-Oct;41(5):67-80. Ukrainian.

Müller EJ, Williamson L, Kolly C, Suter MM.

Outside-in signaling through integrins and cadherins: a central mechanism to control epidermal growth and differentiation?
J Invest Dermatol. 2008 Mar;128(3):501-16.

Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL.
(+)CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis.
Br J Cancer. 2008 Feb 12; [Epub ahead of print]

Bruns I, Steidl U, Fischer JC, Czibere A, Kobbe G, Raschke S, Singh R, Fenk R, Rosskopf M, Pechtel S, von Haeseler A, Wernet P, Tenen DG, Haas R, Kronenwett R.

Pegylated G-CSF mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated G-CSF.
Haematologica. 2008 Feb 11; [Epub ahead of print]

Toth ZE, Leker R, Shahar T, Pastorino S, Szalayova I, Asemenew B, Key S, Parmelee A, Mayer B, Nemeth K, Bratincsak A, Mezey E.

The combination of granulocyte colony stimulatory factor and stem cell factor significantly increases the number of bone marrow derived endothelial cells in brains of mice following cerebral ischemia.
Blood. 2008 Feb 11; [Epub ahead of print]

Quinlan MP, Quatela SE, Philips MR, Settleman J.

Activated Kras, but not Hras or Nras, may initiate tumors of endodermal origin via stem cell expansion.
Mol Cell Biol. 2008 Feb 11; [Epub ahead of print]

McMahon LA, Prendergast PJ, Campbell VA.

A comparison of the involvement of p38, ERK1/2, and PI3K in growth factor-induced chondrogenic differentiation of mesenchymal stem cells.
Biochem Biophys Res Commun. 2008 Feb 8; [Epub ahead of print]

Xu J, Liu X, Jiang Y, Chu L, Hao H, Liu Z, Verfaillie C, Zweier J, Gupta K, Liu Z.

MAPK/ERK signaling mediates VEGF-induced bone marrow stem cell differentiation into endothelial cell.
J Cell Mol Med. 2008 Feb 4; [Epub ahead of print]

Lu ZF, Zandieh Doulabi B, Wuisman PI, Bank RA, Helder MN.

Influence of collagen type II and nucleus pulposus cells on aggregation and differentiation of adipose tissue-derived stem cells.
J Cell Mol Med. 2008 Feb 8; [Epub ahead of print]

Burkert J, Otto W, Wright N.

Side populations of gastrointestinal cancers are not enriched in stem cells.
J Pathol. 2007 Dec 11; [Epub ahead of print]

Li L, Sharma N, Chippada U, Jiang X, Schloss R, Yarmush ML, Langrana NA.

Functional Modulation of ES-Derived Hepatocyte Lineage Cells via Substrate Compliance Alteration.
Ann Biomed Eng. 2008 Feb 12; [Epub ahead of print]

Duan X, Yang L, Dong S, Xin R, Chen G, Guo L.

Characterization of EGFP-labeled mesenchymal stem cells and redistribution of allogeneic cells after subcutaneous implantation.
Arch Orthop Trauma Surg. 2008 Feb 12; [Epub ahead of print]


Kovacevic D, Rodeo SA.

Biological augmentation of rotator cuff tendon repair.
Clin Orthop Relat Res. 2008 Mar;466(3):622-33. Epub 2008 Feb 10.


Jiang J, Chan YS, Loh YH, Cai J, Tong GQ, Lim CA, Robson P, Zhong S, Ng HH.

A core Klf circuitry regulates self-renewal of embryonic stem cells.
Nat Cell Biol. 2008 Feb 10; [Epub ahead of print]

Stem cells,cancer and cancer stem cells

Reya T, Morrison SJ, Clarke MF, Weissman IL.
Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Palo Alto, California 94305, USA. irv@stanford.edu
Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells is that of self-renewal. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells' - rare cells with indefinite potential for self-renewal that drive tumorigenesis.