stem cells

Stem cells used to create organ for transplant

Alex Soojung-Kim Pang — Wed, 19 Nov 2008 07:40:50 -0800

Description

One of the potential uses of stem cells is in creating organs for transplant. In principle, stem cells taken from a patient should be recognized by the body, thus avoiding problems with organ rejection. However, creating those organs-- particularly anything with a complex, three-dimensional structure-- has been difficult. The New Scientist reports that

A Colombian woman has become the world's first recipient of windpipe tissue constructed from a combination of donated tissue and her own cells.

Stem cells harvested from the woman's bone marrow were used to populate a stripped-down section of windpipe received from a donor, which was then transplanted into her body in June.

"Surgeons can now start to see and understand the very real potential for adult stem cells and tissue engineering to radically improve their ability to treat patients," says Martin Birchall, professor of surgery at the University of Bristol, UK, and a member of the team which constructed the windpipe tissue....

Spanish doctors started the process by taking a 7-centimetre section of windpipe from a deceased donor.

Researchers at the University of Padua, Italy, led by Maria Teresa Conconi, then used detergent and enzymes to purge the donated windpipe of all the donor's cells. After six weeks, all that was left was a solid scaffold of connective tissue.

Meanwhile, Birchall and his colleagues in Bristol took the stem cells from the patient's bone marrow and coaxed them in the lab into developing into the cartilage cells that normally coat windpipes.

Finally, the patient's cells were coated onto the donated tracheal scaffold over four days in a special bioreactor built at the Polytechnic of Milan in Italy.

The patient received the finished organ in June at the Hospital Clinic, Barcelona, where surgeon Paolo Macchiarini replaced Castillo's damaged trachea with the newly constructed tissue.

As Ramez Naam comments,

In principle the same technique could be used to regrow all sorts of organs, though actually growing the organs and having the right scaffolding is still extremely tricky and has only been demonstrated for a few organs. Even so, progress is being made at a remarkable rate.

Biomedical Sciences and Biotechnology

Source

http://www.newscientist.com/article/dn16072-woman-receives-windpipe-built-from-her-stem-cells.html?DCMP=OTC-rss&nsref=online-news
http://www.morethanhuman.org/2008/11/woman-gets-new-windpipe-grown-from-her.htm

Big pharmas and clinical stem cell research

Attila Csordas — Mon, 29 Sep 2008 10:01:30 -0700

Description

After many years of more or less ignoring the topic, big pharmaceutical companies (revenue in excess of $3 billion) finally are paying attention to stem cells as vehicles of drug testing and future regenerative medicine therapies. The pioneering and highly risky stem cell field has been so far mostly the domain of academic laboratories and small biotech companies.
But these days big pharmas finally started to cooperate with both academia and startups and invest in the range of couple millions of dollars. Some signs of the upcoming trend: GlaxoSmithKline and the Harvard Stem Cell Institute (HSCI) recently (in July, 2008) announced a five-year, $25 million-plus collaborative agreement while Pfizer has already invested $3 million in shares of EyeCyte a La Jolla based early stage stem/progenitor cell-based ophthalmology research and development company.
Stem Cells for Safer Medicines, or SC4SM, a collaboration to develop stem cells for safety testing of new drugs through a public-private partnership and an independent not-for-profit company is backed by 3 European big pharmas, GlaxoSmithKline, AstraZeneca and Roche.
A higher form of involvement means in-house research labs and Pfizer is on that road too with its functional “regenerative medicine unit” in Cambridge, Mass. and with the plans to open another similar shop in the other Cambridge, overseas around this November.
On the drug testing platform stem cell mediated results can be expected much sooner than in the case of an efficient and safe stem cell therapy. According to a 2006 data it takes $1.318 billion and 10-15 years to develop a traditional pharmaceutical drug but no data available on the costs and timeframe of a stem cell based regenerative therapy.

If big pharmas are really risk-taking and invest enough money in stem cell trials in the range of hundreds of million of dollars and if no serious complications occur during the trials then by 2020 or by and large within a decade we can expect some important results from those companies.

But here we should really consider the state of global economy as a big ballast and the tough times in the pharma industry.

What can be expect though with a bigger certainty is that within a decade most of the big pharmas will seriously flirt with stem cells the in the form of setting up in-house research labs, investing in biotech startups and collaborating with the academy.

Sources:

http://www.sc4sm.org/
http://seekingalpha.com/article/79266-pharmaceutical-facts-investors-should-know
http://en.wikipedia.org/wiki/List_of_pharmaceutical_companies

Signals

GlaxoSmithKline collaborates with the Harvard Stem Cell Institute

Pfizer's growing and various interests in stem cells

GlaxoSmithKline collaborates with the Harvard Stem Cell Institute

Attila Csordas — Fri, 26 Sep 2008 05:28:00 -0700

Description

GlaxoSmithKline, the world’s second-biggest pharmaceutical company and the Harvard Stem Cell Institute (HSCI) recently (in July, 2008) announced a five-year, $25 million-plus collaborative agreement.

GSK’s investment, one of the largest by a pharmaceutical company in stem cell science, will support innovative research at Harvard University and in at least four Harvard-affiliated hospitals in the areas of neuroscience, heart disease, cancer, diabetes, musculoskeletal diseases and obesity. In addition, GSK will fund an annual grant, which supports early stage research in stem cell biology, as part of HSCI’s seed grant program “GSK believes stem cell science has great potential to aid the discovery of new medicines by improving the screening, identification and development of new compounds. We have carefully chosen the Boston biomedical community to collaborate with on this important venture. It has the highest concentration of leading stem cell scientists, and the Harvard Stem Cell Institute is the epicentre of that community,” said Patrick Vallance, Head of Drug Discovery at GSK.

Biomedical Sciences and Biotechnology

Source

http://www.gsk.com/media/pressreleases/2008/2008_pressrelease_10089.htm
http://www.xconomy.com/boston/2008/07/25/harvard-stem-cell-institute-wins-25-million-investment-from-glaxosmithkline/
http://www.hsci.harvard.edu/
http://www.gsk.com/

Pfizer's growing and various interests in stem cells

Attila Csordas — Fri, 26 Sep 2008 03:46:44 -0700

Description

Pfizer Inc. is one of the biggest research-based pharmaceutical company and ranks number one in the world in sales. The company opened a “regenerative medicine unit” in Cambridge, Mass. last year and now moves to the other Cambridge, U.K. to open another similar shop around November. On the other hand Pfizer has already invested $3 million in shares of EyeCyte a La Jolla based early stage stem/progenitor cell-based ophthalmology research and development company. The growing interest can be partly explained by the role that induced pluripotent stem cells can play in drug testing and the first uses will probably be in early-stage safety testing. The risk-taking in the new and unknown field is especially interesting considering the tough times in the pharma industry.

These cells will be tremendous in drug discovery,” an R&D exec told Reuters. “They will help us understand personalized medicine, genetic variation, ethnic populations, what biomarkers to follow.” John McNeish will run Pfizer's U.S. unit, which will focus on heart disease and diabetes. In November, the company plans to open a standalone regenerative medicine unit in Cambridge, United Kingdom, to focus on research in ophthalmology and diseases of the central nervous system. McNeish said the overall operation will eventually have 50 to 60 scientists working on stem cell therapies, and they are working with academic researchers and smaller biotech companies.

Biomedical Sciences and Biotechnology

Source

http://www.reuters.com/article/reutersEdge/idUSTRE48MBY020080923
http://blogs.wsj.com/health/2008/09/24/pfizer-moves-into-stem-cell-research/
http://en.wikipedia.org/wiki/Pfizer
http://www.medicalnewstoday.com/articles/112558.php

The 'stem cell matrix':classifying stem cell lines based on global gene expression profiles

Attila Csordas — Tue, 26 Aug 2008 09:24:16 -0700

Description

Large scale classification of the numerous stem/progenitor cell lines based on their regenerative potential and phenotypes is an increasingly important academic/clinical task. Finally using a collection of about 150 human cell samples, American researchers created a database of global gene expression profiles using Illumina’s BeadArray technology. During the bioinformatic analysis suitable machine learning algorithms were used to understand and codify the phenotypes of stem cells.

"We report here the creation and analysis of a database of global gene expression profiles (which we call the 'stem cell matrix') that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent and differentiated cell types. Using an unsupervised clustering method to categorize a collection of approx 150 cell samples, we discovered that pluripotent stem cell lines group together, whereas other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis we uncovered a protein–protein network (PluriNet) that is shared by the pluripotent cells (embryonic stem cells, embryonal carcinomas and induced pluripotent cells). Analysis of published data showed that the PluriNet seems to be a common characteristic of pluripotent cells, including mouse embryonic stem and induced pluripotent cells and human oocytes. Our results offer a new strategy for classifying stem cells and support the idea that pluripotency and self-renewal are under tight control by specific molecular networks."

Biomedical Sciences and Biotechnology

Source

Franz-Josef Müller, Louise C. Laurent, Dennis Kostka, Igor Ulitsky, Roy Williams, Christina Lu, In-Hyun Park, Mahendra S. Rao, Ron Shamir, Philip H. Schwartz, Nils O. Schmidt & Jeanne F. Loring: Regulatory networks define phenotypic classes of human stem cell lines
Nature , | doi:10.1038/nature07213; Received 15 December 2007; Accepted 26 June 2008; Published online 24 August 2008
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature07213.html

Selling Stem Cells

Matt Daniels — Wed, 09 Apr 2008 09:24:39 -0700

Description

BioTime's Michael West wants to standardize and commercialize stem cells for scientist.

A California biotech company headed by Michael West, a prominent scientist and entrepreneur involved in stem cell research, plans to supply scientists working with stem cells the tool they most need to develop and test novel therapies--a reliable and reproducible source of the cells.

Stem cells hold great promise for medicine, both as a potential source of replacement cells for damaged organs and as a scientific resource to study disease and develop and test new drugs. But to realize that promise, scientists have to figure out how to make their products on an industrial scale. "It's clear we'll need a much better strategy for reliably and reproducibly generating large numbers of specific cell types," says Arnold R. Kriegstein, director of the Institute for Regenerative Medicine at the University of California, San Francisco. "Most studies until now have stopped short of doing this."

The very qualities that make stem cells so desirable--the ability to self-replicate and develop into many types of cells--can also make them difficult to control. For example, two cell lines produced the same way but from different starting materials don't always behave the same, a property that's essential for both cell-based therapies and scientific studies.

West, CEO of BioTime and its subsidiary, Embryome Sciences, plans to sell lines of cells that he dubs "human embryonic progenitors"--cells that have inched partway along the continuum from embryonic stem cell to differentiated adult cell. West and collaborators published a paper last week describing their efforts to generate cells that reproduce only the same type of cells, theoretically creating a better-defined cell product.

Source

http://www.technologyreview.com/Biztech/20533/

http://www.biotimeinc.com/

Stem Cell Solution? A company claims to have made safer reprogrammed stem cells

Matt Daniels — Mon, 10 Mar 2008 09:31:34 -0700

Description

Stem-Cell Solution?
A company claims to have made safer reprogrammed stem cells
Thursday, February 28, 2008
(Emily Singer, MIT Technology Review)

PrimeGen, a small biotech company based in Irvine, CA, says that it has solved one of the major hurdles in using reprogrammed stem cells for human therapies. Last year, scientists announced that they had successfully created embryonic-like stem cells from adult cells, circumventing the ethical and technical hurdles associated with embryonic stem cells. But the method used viruses to deliver genes, raising concerns over cancer risk.

According to an article in Forbes,

PrimeGen claimed Tuesday it had circumvented this problem. Instead of genes, it uses unspecified carbon-based "delivery particles" to insert four proteins into cells to stimulate the reprogramming process. This caused some of the cells to revert to being much like embryonic stem cells, PrimeGen said. PrimeGen said it has done the experiment with retinal, skin and testicular cells.

"Our goals are ambitious--we believe with this therapy, we can be in clinic in 2010," said PrimeGen president John Sundsmo in an interview. He said he couldn't release details on what the delivery particles are until the company finalizes an agreement with a corporate partner.

However, some scientists are skeptical. Rather than being published in a peer-reviewed scientific journal, the findings were released during a brief presentation at a stem-cell industry conference in New York.

According to Forbes,

Many outside scientists said they weren't familiar with the work and weren't quite sure what to think. "Until the work goes through [peer-review], it would be difficult to evaluate," says James Thomson, the researcher at University of Wisconsin, Madison, who created the first embryonic stem cells in 1998. George Daley, of Harvard University, said he was "pretty suspicious of publication by press release."

Nonetheless, "if this is real it really is a significant step," says Arnold Kriegstein, director of the Institute for Regenerative Medicine at U.C.-San Francisco. "They could be on to something."

Source

Using by-product tissues as stem cell sources

Attila Csordas — Fri, 23 Nov 2007 19:01:35 -0800

Description

I call by-product human tissues the ones that are not needed for the human body after filling their essential function in the body, like menstrual blood, amniotic fluid, placenta and umbilical cord blood. It is a somewhat very positive idea that these human tissues previously considered as waste products, the placenta (1) the umbilical cord (2) are radically reinterpreted as valuable sources of prospective therapies due to the current results of stem cell research and regenerative medicine.

Exactly this reinterpretation is taking place now with the cells of the regularly produced menstrual blood flow as the first commercially available menstrual stem cell service (managed through Fedex), C’elle was launched by cord blood banker Cryo-Cell.

According to a freshly published article (3): "Angiogenesis is a critical component of the proliferative endometrial phase of the menstrual cycle. Thus, we hypothesized that a stem cell-like population exist and can be isolated from menstrual blood. Mononuclear cells collected from the menstrual blood contained a subpopulation of adherent cells which could be maintained in tissue culture for >68 doublings. and retained expression of the markers CD9, CD29, CD41a, CD44, CD59, CD73, CD90 and CD105, without karyotypic abnormalities. Proliferative rate of the cells was significantly higher than control umbilical cord derived mesenchymal stem cells, with doubling occurring every 19.4 hours. These cells, which we termed "Endometrial Regenerative Cells" (ERC) were capable of differentiating into 9 lineages: cadiomyocytic, respiratory epithelial, neurocytic, myocytic, endothelial, pancreatic, hepatic, adipocytic, and osteogenic. Additionally, ERC produced MMP3, MMP10, GM-CSF, angiopoietin-2 and PDGF-BB at 10-100,000 fold higher levels than two control cord blood derived mesenchymal stem cell lines. Given the ease of extraction and pluripotency of this cell population, we propose ERC as a novel alternative to current stem cells sources."

So the characteristics of these menstrual stromal cells could easily be compared to the more established mesenchymal stromal cells from the bone marrow but their collection is non-invasive and pain free I’d like to highlight 2 differences: the menstrual derived cells express embryonic like cell surface markers like SSEA and Oct4 (warning: maybe Oct4 is not important for self-renewal and maintenance of somatic stem cells at all) compared to the mesenchymal cells, while the mesenchymal stromal cells are better in their immunological properties as in some cases they are even able to suppress immunological reactions, while the menstrual cells said to be demonstrated a weak stimulatory response which suggests potential use in first-degree relatives (if the source is the mother, it is probably no good for the father) but not in distant relatives.

The professional jargon would rather call those cells stromal cells as they are not adult stem cells in the sense of being in the adult organism throughout the life and retaining some renewing capacity.

What are the implications of this work?

the collection and storing of by-product tissues as stem cell sources can easily be commercialized and opens up a big marketplace in biotech;
The recycling of by-product tissue as stem cell sources can become the strong rivals of embryonic or adult somatic stem cells concerning future regenerative medicine therapies;
The recycling of by-product tissue as stem cell sources is ethically uncontroversial compared to embryonic stem cells.

Peer review literature

1. Miki et al. Stem Cell Characteristics of Amniotic Epithelial Cells Stem Cells Vol. 23 No. 10 November 2005, pp. 1549 -1559 http://stemcells.alphamedpress.org/cgi/content/short/23/10/1549
2. Secco et al.: Multipotent Stem Cells from Umbilical Cord: Cord is Richer than Blood! Stem Cells. 2007 Oct 11
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17932423&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubm...
3. Meng et al. Endometrial regenerative cells: A novel stem cell population Journal of Translational Medicine 2007, 5:57doi:10.1186/1479-5876-5-57 http://www.translational-medicine.com/content/5/1/57

Blog:

Pimm: Collect and FedEx menstrual stem cells with the C’elle kit: the next flow
http://pimm.wordpress.com/2007/11/06/collect-and-fedex-menstrual-stem-cells-with-the-celle-kit-the-next-flow/

Signals

Finding new adult stem cell repair mechanisms

Attila Csordas — Fri, 23 Nov 2007 17:09:46 -0800

Description

A focus shift is taking place in current adult stem cell biology. So far the two main candidate repair mechanisms for adult stem cells were transdifferentiation and fusion. The concept that lineage specific adult stem cells can change their fate, is called transdifferentiation (Mezey et al., 2000). The other basic and proposed regenerative mechanism is cell fusion between the transplanted cells and the damaged tissue cells (Nygren et al., 2004, Nat Med. One population of bone marrow derived cells, the mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) (Prockop, Science) are able both to self-renew and differentiate into various cell types (cartilage, bone, muscle, tendon, ligament, and fat) in vitro and are present in many other tissues including fat, bone, skin, umbilical cord blood.(4)

Adult stem cells originally attracted attention because of the their stem cell-like properties, but the cells frequently repaired injured tissues and produced functional improvements without much evidence of either engrafment or differentiation. In transplantation trials the levels of donor MSCs detected in bone, skin and other tissues was less than 1% and it seemed probable that they are able to repair tissues in other and multiple ways too.

Impact:

Future areas of research based mainly on Prockop DJ. Clin Pharmacol Ther. 2007 Sep;82(3):241-3.;
Secreted cytokines and chemokines: Recently, stem cell based regeneration in the heart (reviewed in Srivastava-Ivey, 2006, Nature) by transdifferentiation has been challenged and it was indicated that bone marrow derived mesenchymal stem cells do not transdifferentiate into hepatocytes (Murry et al, 2004, Nature). Instead it was suggested for the myocardium at least, that paracrine factors secreted by the bone marrow cells, like thymosin beta4 could be cardioprotective or angiogenic. (Gnecchi et al, 2006, Bock-Marquette et al 2004, Nature);
Stimulation of tissue stem/progenitors;
Immunomodulatory effects of stem cells, anti-immune reactions: MSCs suppressed the mixed lymphocyte reaction in culture and shown to improve engraftment of bone marrow and graft versus host disease in patients (Le Blanc and Ringden, 2006);
Anti-inflammatory effects of MSCs: suppression of inflammation;
Mitochondrial transfer, in vitro: the transfer of mitochondria from hMSCs or fibroblast were able to rescue the aerobic respiration of respiration deficient cells in vitro (Spees et al, 2006).

Prockop DJ. "Stemness" does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs).Clin Pharmacol Ther. 2007 Sep;82(3):241-3.
Spees JL, Olson SD, Whitney MJ, Prockop DJ. Mitochondrial transfer between cells can rescue aerobic respiration.
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1283-8. Epub 2006 Jan 23.
Blog: Pimm: Bone marrow derived adult stem cells: which way to go? http://pimm.wordpress.com/2007/02/22/bone-marrow-derived-adult-stem-cells-which-way-to-go/

Signals

Using cancer stem cells for regenerative medicine

Attila Csordas — Fri, 23 Nov 2007 10:35:55 -0800

Description

The trendy cancer stem cell theory highlights that there is a functional hierarchy between different tumour cells and only a small portion, the so called cancer stem cells, have crucial role in initiating tumour growth. In a stronger form the assumption is that only a tiny minority of tumor cells have the ability to initiate tumor formation.

This assumption was confirmed in the case of blood (1) breast (2) and brain(3) for example. These cells are similar to stem cells in their renewing capability as they can maintain the population through the series of division as well as giving rise to a large population of differentiated progeny that make up the bulk of the tumor. Cancer stem cells are posing multiple threats: repairing the radiation induced DNA damage better than nonstem cancer cells, they can stimulate angiogenesis, the formation of new blood vessels that support tumor growth and can drive metastasis, the spread of tumor in the body. Indeed, in human pancreatic cancer a distinct subpopulation of migrating cancer stem cells turned out to be essential for tumor metastasis different from the ones responsible for tumor growth (4).

Based on the stem cell theory, a new therapeutic approach of cancer is delineated which can induce differentiation of tumour cells rather then killing them. Indeed a very natural and useful stem cell targeted therapy by concept: redifferentiate cancer stem cells into harmless and in some cases useful functional tissue cells. I call it the concept of cancer regenerative medicine: redifferentiate all the tumour initiating cancer stem cells in a patient into functional tissue and organ cells.

In a Nature article (5) Piccirillo et al. addressed the question whether the stem-like tumour initiating cell subpopulation of a glioblastoma, marked with a specific antigen, CD 133+ can be differentiated with Bone Morphogenetic Protein (BMP) into a functional type of brain cells? Glioblastoma (GBM) is the most common adult malignant brain tumour, CD133+ is a neural precursor cell marker and the members of the BMP family make neural precursor cells differentiatie into mature astrocytes, glial cells. So they were dissociating solid tumour samples into single-cell suspensions and were testing their response to BMP. The large picture is that BMP treatment (specially BMP4) reduced cancer cell proliferation, induced astrocyte-like differentiation, effectively blocks the tumour growth and prolonges survival:

These findings show that the BMP–BMPR signalling system—which controls the activity of normal brain stem cells—may also act as a key inhibitory regulator of tumour-initiating, stem-like cells from GBMs and the results also identify BMP4 as a novel, non-cytotoxic therapeutic effector, which may be used to prevent growth and recurrence of GBMs in humans.

Problem could be that certain cancer cells survived the BMP-treatment which can lead to recurrence at a longer latency. This problem could be solved with improved purification of the subpopulation of CD133+ cells, so true cancer stem cells are expected at the exit!

Combined with classical therapy BMP, redifferentiation treatment can reduce the lethality of cancer patients.

Skeptics of cancer stem cell theory have arguments too: Some argue that the original cancer-causing mutations can strike more developmentally advanced, although still immature, progenitor cells. Stem cells of a given type of cancer may arise from different cells and the origin varies from patient to patient- all the work has involved transplanting human cancer cells into immunodeficient mice. This has raised concerns that the experiments do not accurately reflect what happens during cancer development in humans.

There are several implications of this work.

“By gaining a sophisticated understanding of how normal and cancer stem cells differ, we’ll be able to design a new class of drugs that is less toxic”;
Searching for markers specific for cancer stem cell populations;
New clues on cancer development by examining cancer stem cells focusing on the different the signalling pathways needed for the maintenance and development;
Convergence of cancer and stem cell research, as both are very well funded.

Peer review literature:

1. Lapidot et al: A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994 Feb 17;367(6464):645-8.
http://www.ncbi.nlm.nih.gov/sites/entrez?holding=npg&cmd=Retrieve&db=PubMed&list_uids=7509044&dopt=AbstractPlus

2. Al-Hajj et al: Prospective identification of tumorigenic breast cancer cells PNAS 2003 100(7):3983-3988 http://www.pnas.org/cgi/content/abstract/100/7/3983

3. Singh et al. Identification of human brain tumour initiating cells. Nature. 2004 Nov 18;432(7015):396-401.
http://www.ncbi.nlm.nih.gov/sites/entrez?holding=npg&cmd=Retrieve&db=PubMed&list_uids=15549107&dopt=AbstractPlus

4. Hermann et al. Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer. Cancer Stem Cell Volume 1, Issue 3, 13 September 2007, Pages 313-323 doi:10.1016/j.stem.2007.06.002

5. Piccirillo et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006 Dec 7;444(7120):761-5.
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17151667&query_hl=7&itool=pubmed_docsum

Professional media:

Jean Marx: Cancer's Perpetual Source? Science 24 August 2007:
Vol. 317. no. 5841, pp. 1029 - 1031 DOI: 10.1126/science.317.5841.1029
http://www.sciencemag.org/cgi/content/summary/317/5841/1029

Blogosphere:

Pimm: Redifferentiating brain tumour stem cells: the concept of cancer regenerative medicine
http://pimm.wordpress.com/2006/12/14/redifferentiating-brain-tumours-the-concept-of-cancer-regenerative-medicine/

Pimm: Biopolis profile and cancer stem cells in current Cell Stem Cell http://pimm.wordpress.com/2007/10/05/biopolis-profile-and-cancer-stem-cells-in-current-cell-stem-cell/

Signals

Reprogramming differentiated cells offers alternative to embryonic stem cells

Attila Csordas — Thu, 22 Nov 2007 08:47:03 -0800

Description

Stem cells are able to renew themselves and could differentiate into other type of cells. Regenerative medicine is the science and technology built around stem cells’ regenerative capacity. Successful reprogramming of differentiated human somatic cells into a pluripotent, embryonic stem (ES) cell-like state would allow creation of patient- and disease-specific stem cells instead of using controversial embryonic stem cells. The generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors was reported (1).

American (2) and Japanese (3) researchers recently demonstrated that the same technique (but with different set of 4 genes) can turn human cultured skin cells into induced pluripotent stem (iPS) cells that meet the defining criteria for human ES cells and are similar to ES cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. These cells could differentiate into cell types of the three germ layers in vitro and in vivo in teratomas. The significant exception is that iPS cell are not derived from the embryo nor were made by the therapeutical cloning technique in in which the nucleus of a differentiated cell is placed in an oocyte that is then activated to divide to form an embryo.

What are the future implications of these findings?

Similar to human ES cells, human iPS cells should prove useful for studying the development and function of human tissues.
Disease and patient specific cells: the reprogrammed induced pluripotent cells could be made from patients with known diseases. If the root causes of disease were genetic that could be a better way to study disease, say genetically matched cells from patients would enable them to study complex diseases, like Alzheimer’s, in the laboratory.
Discovering and testing new drugs: Human iPS cells should make it easier to generate panels of cell lines that more closely reflect the genetic diversity of a population, and should make it possible to generate cell lines from individuals predisposed to specific diseases.
For transplantation therapies based on these cells, with the exception of autoimmune diseases, patient-specific iPS cell lines should largely eliminate the concern of immune rejection.
If it works, the technique -- technically known as somatic cell dedifferentiation -- promises to solve the two great downfalls involved in producing embryonic stem cells: the controversial destruction of embryos and reliance on a limited supply of eggs.
The new method includes potentially risky steps, like introducing a cancer gene with engineered viruse. But stem cell researchers say they are confident that it will not take long to perfect the method and that today’s drawbacks will prove to be temporary. It is important to understand, however, that before the cells can be used in the clinic, additional work is required to avoid vectors that integrate into the genome, potentially introducing mutations at the insertion site.
The method is a direct rival of the other reprogramming technique called terapeuthical cloning based on somatic cell nuclear transfer.
The reprogrammed skin cells may yet prove to have subtle differences from embryonic stem cells that come directly from human embryos, and further work is needed to determine if human iPS cells differ in clinically significant ways from ES cells.

Peer-review literature:
1. K. Takahashi, S. Yamanaka, Cell 126, 663 (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126:663-76

2. Takahashi et al. (2007) Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined
Factors Cell (2007), doi:10.1016/j.cell.2007.11.019 PDF

3. Yu et al. (2007) Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells Science, Published online 20 November 2007; 10.1126/science.1151526

Media coverage:
Nature Reports Stem Cell: Human reprogramming changes everything, and nothing

Wired Science: Skin Cell-to-Stem Cell Alchemy 'Like Turning Lead Into Gold'

New York Times: Scientists Bypass Need for Embryo to Get Stem Cell

Signals

Active Biomaterials for Regenerative Medicine

Alex Soojung-Kim Pang — Tue, 23 Oct 2007 11:10:30 -0700

Description

Research on active biomaterials for implantation in the human body could lead to in-situ repair and regeneration of damaged tissue as an alternative to surgery and a cure for some diseases.

The first generation of manufactured biomaterials emerged in the 1960s; they were prosthetic parts made of inert substances that were intended to be placed inside the body with minimal likelihood of immune system rejection. A second generation employed bioactive materials that could elicit a desired action and reaction from the body. Employing research at the molecular level, a new generation of biomaterials is in development; these novel materials are being designed to stimulate specific cellular responses, thereby activating genes to stimulate the regeneration of live tissue. While research on active biomaterials is new, the development of biomaterials has been under way for 40+ years.

If regenerative medicine based on active biomaterials can be developed, it is conceivable that the body will be able to heal itself internally, as it does with a cut or scrape today. Tissue regeneration shows the greatest promise with the use of stem cells, so new developments in stem cell research are an important part of the effort. Nanomaterials may provide solutions to the significant challenge of developing mechanisms that will support blood flow in engineered materials.

Implications:
* Vast enhancement of the human body's ability to repair itself
* Potential for reversal of organ damage resulting from disease
* Decreased use of surgery

Early Indicators:
* Employment of biomaterials for skin regeneration in acute wounds such as burns and as scaffolds for guided nerve regeneration at the Institute for Regenerative Medicine at Wake Forest University
* Successful application of research by Stephan Heller (Harvard/Stanford) on using adult and embryonic stem cells to regenerate hearing tissues, leading to improvement of hearing loss due to aging

What to Watch:
* Breakthroughs in stem cell research, nanomaterials and microtextiles lead to procedures that can be tested in clinical trials.

Parallels/Precedents:
* Development of the first and second generations of manufactured biomaterials

Enablers/drivers:
* Better understanding of the basic mechanisms involved in cell growth and differentiation into different types of tissue
* Resolution of the ethical dilemma associated with the use of embryonic stem cells
* Rapid aging of the population in Western societies, outpacing medicine's ability to perform invasive surgeries and the human and financial resources to do so
* Ongoing nanomaterial research