Scientists sound alarm over DNA editing of human embryos

Scientists sound alarm over DNA editing of human embryos
Exper ts call for halt in research to work out safety and ethics issues.
12 March 2015
http://www.nature.com/news/scientists-sound-alarm-over-dna-editing-of-human-embryos-1.17110

Amid rumours that precision gene-editing techniques have been used to modify the DNA of human embryos, researchers have called for a moratorium on the use of the technology in reproductive cells.

NPR version:
https://franzcalvo.wordpress.com/2015/03/29/scientists-urge-temporary-moratorium-on-human-genome-edits

Stem cell factories found inside teeth

Glial origin of mesenchymal stem cells in a tooth model system
Nina Kaukua, et al.
Nature (2014). Published online  27 July 2014
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13536.html

Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair.
The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues.
The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells.
These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives.
Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium. It has been thought for decades that the dental mesenchymal stem cells giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue.

Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique6 with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.

journalistic version:
http://news.sciencemag.org/biology/2014/07/unexpected-stem-cell-factories-found-inside-teeth

MSCT for refractory SLE

Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study
Dandan Wang, et al. (Beike Biotechnology Co., Ltd.)
Arthritis Research & Therapy 2014, 16:R79
http://arthritis-research.com/content/16/2/R79

Conclusion: UC-MSCT results in satisfactory clinical response in SLE patients.
However, in our present study, several patients experienced disease relapse after 6 months, indicating the necessity to repeat MSCT after 6 months.

MSCs are multipotent, nonhematopoietic progenitor cells that are currently being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential, together with their effects on immune responses, make them a promising therapeutic tool for the treatment of patients with severe and refractory autoimmune diseases.

related:
Stem-Cell Therapy in China Draws Foreign Patients
March 18, 2008
http://www.npr.org/templates/story/story.php?storyId=88123868

Young mouse blood rejuvenates old brains

Young blood rejuvenates old brains 
Nature Medicine 20, 582–583 (2014)
http://www.nature.com/nm/journal/v20/n6/full/nm.3597.html

Villeda et al. show that young blood contains a factor that reverses some aspects of age-related cognitive impairment in mice. Parabiosis in which aged mice are conjoined with aged mice such that their circulatory systems are connected results in no change in synaptic plasticity.
However, parabiois between aged and young mice results in increased expression of proteins involved in synaptic plasticity, and an increased number of dendritic spines and synaptic plasticity in aged mice, as measured by enhanced long-term potentiation in these mice.

update:
http://www.sciencemag.org/news/2016/08/young-blood-antiaging-trial-raises-questions

related:

https://franzcalvo.wordpress.com/2016/03/19/staying-sharp-henry-emmons-md

Crashing Through

Crashing Through
by Robert Kurson
May 24, 2007
http://www.npr.org/templates/story/story.php?storyId=10382528

Michael May was blinded at age three, and lived 42 years of his life without sight. In 1999, at age 45, May was given the possibility to see again through a revolutionary stem-cell transplant surgery.

related:
macular degeneration
http://www.npr.org/2014/10/14/356202695/study-finds-human-stem-cells-may-help-to-treat-patients

http://www.npr.org/blogs/health/2014/10/14/346174070/embryonic-stem-cells-restore-vision-in-preliminary-human-test

Healing hearing: regeneration of sensory hair cells

The delicate sensory hair cells in the inner ear can be damaged by loud noise.

Baby Steps Toward Healing Hearing
Science. 20 February 2014
http://news.sciencemag.org/biology/2014/02/baby-steps-toward-healing-hearing

Hairy situation. Just like in human ears, the delicate sensory hairs in the rat inner ear (shown above) can be damaged by loud noise, chemicals, and infection.

There is no biological cure for deafness—yet. We detect sound using sensory cells sporting microscopic hairlike projections, and when these so-called hair cells deep inside the inner ear are destroyed by illness or loud noise, they are gone forever. Or so scientists thought. A new study finds specific cells in the inner ear of newborn mice that regenerate these sensory cells—even after damage, potentially opening up a way to treat deafness in humans.

Researchers knew that cells in the inner ear below hair cells—known as supporting cells—can become the sensory cells themselves when stimulated by a protein that blocks Notch signaling, which is an important mechanism for cell communication. Albert Edge, a stem cell biologist at Harvard Medical School in Boston, and his colleagues, attempted to identify the exact type of supporting cells that transform into sensory ones and fill in the gaps left by the damaged cells.

related:
http://www.npr.org/sections/health-shots/2015/07/08/421204204/genetic-tweaks-are-restoring-hearing-in-animals-raising-hopes-for-people
precision medicine

Grow Your Own Organs

Grow Your Own Organs
BBC. November 2013
http://www.bbc.com/specialfeatures/horizonsbusiness/episode/technobody/?autoplay=true&vid=p01lkt88
Pioneer scientist Dame Julia Polak speaks to Adam Shaw about one day growing our own organs

Before we turned up to interview our main guest for this programme, we were all asked to confirm we didn’t have a cold, were well and certainly did not have anything infectious. We were filming a leading light of medicine who, because she has had a heart and lung transplant, was very susceptible to any disease. She is typical of a new frontier of medical advance in which the future of medicine lies not in the hands of traditional medical experts but with bio-engineers

This new technology builds new body parts from the cells up, enabling patients to receive new transplants from tissues grown from their own bodies. It is a science in its infancy but it has the power to transform the way we think of medicine and ageing.

Imperial College London. Dame Julia Polak is founder of the Tissue Engineering and Regenerative Medicine Centre at Imperial College. Extraordinarily, in 1995 she was also the recipient of a heart and lung transplant, making her one of the longest survivors of the procedure. It was an experience which led her to a pioneering career in the fledgling science of growing new organs from cells.

The new technologies mean scientists can create a three-dimensional structure which can be implanted into the patient. There have been some initial clinical trials for the heart and for the bladder.

A group in the US created a three-dimensional tissue engineered bladder in the laboratory and implanted it into children and eight years on the bladder is still working.

Dame Julia Polak admits the new knowledge may mean, in theory, we could live forever.
“Who knows what will happen in five or ten years but there are lots of hurdles to overcome because there are regulatory hurdles, financial hurdles and creating an atmosphere of really multidisciplinary teams including everybody including patients

Stanford University in California.
Professor Ada Poon has developed a revolutionary prototype device. Powered and controlled by radio waves generated outside of the body, it is so small it could move through a patient’s bloodstream, collecting medical data or delivering medication.
This could be the start of miniature robot doctors searching through your body, looking for problems and fixing them.

It sounds like a movie but it’s probably too unbelievable for fiction. For the whole truth about the possibilities of future medicine, tune into our Horizons programme on robotics and the future of medicine.

=================

Technobody A new science with the power to transform medicine and ageing http://www.bbc.com/specialfeatures/horizonsbusiness/episode/technobody

Key megatrend: Technobody

tissue engineering

Multiple sclerosis: An old drug (benztropine) plays a new trick

a, rat oligodendrocyte progenitor cells … agents that would induce differentiation of oligodendrocytes, which produce myelin basic protein (MBP). b, Benztropine enhanced axon myelination when added to a co-culture of oligodendrocyte progenitors and neurons. c, Benztropine promoted remyelination, … alleviated disease symptoms such as hind-leg and tail paralysis.

Multiple sclerosis: An old drug plays a new trick
Nature 502, 314–315 (17 October 2013)
http://www.nature.com/nature/journal/v502/n7471/full/nature12694.html
Hartmut Wekerle & Edgar Meinl

A drug already used to treat Parkinson’s disease induces repair of the damage that occurs to the myelin sheath around nerve fibres during multiple sclerosis.
The finding offers new therapeutic avenues for this disease.

———————-

https://www.esclerosismultiple.com/actriz-selma-blair-tiene-esclerosis-multiple

Cerebral organoids

Pluripotent stem cells can be derived as either embryonic stem (ES) cells from the inner cell mass of the blastocyst (70–200-cell embryos) or induced pluripotent stem (iPS) cells through the reprogramming of adult cell types.

Cerebral organoids model human brain development and microcephaly
Nature 501, 373–379 (19 September 2013)
Madeline A. Lancaster, et al.
http://www.nature.com/nature/journal/v501/n7467/full/nature12517.html

we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells.

Developmental neuroscience: Miniature human brains
Nature 501, 319–320 (19 September 2013)
http://www.nature.com/nature/journal/v501/n7467/full/nature12552.html
Oliver Brüstle

Reprogramming in vivo produces teratomas

a, The preimplantation embryo, or blastocyst, consists of the inner cell mass that gives rise to the fetus. Its outer cells, the trophoblast, develop into the extraembryonic tissues of the placenta. Embryonic stem (ES) cells, derived from blastocysts, self-renew in culture and are pluripotent, giving rise to all cell types of the growing embryo. ES cells rarely exhibit totipotent-like features such as the potential to form extraembryonic tissues.

Reprogramming in vivo produces teratomas and iPS cells with totipotency features
Nature 502, 340–345 (17 October 2013)
María Abad et al.
http://www.nature.com/nature/journal/v502/n7471/full/nature12586.html

Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of in vivo reprogramming within tissues.
Here we show that transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur in vivo.
Analyses of the stomach, intestine, pancreas and kidney reveal groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of in situ reprogramming.
By bone marrow transplantation, we demonstrate that haematopoietic cells can also be reprogrammed in vivo.
Notably, reprogrammable mice present circulating iPS cells in the blood and, at the transcriptome level, these in vivo generated iPS cells are closer to embryonic stem cells (ES cells) than standard in vitro generated iPS cells.
Moreover, in vivo iPS cells efficiently contribute to the trophectoderm lineage, suggesting that they achieve a more plastic or primitive state than ES cells.
Finally, intraperitoneal injection of in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic markers.
We conclude that reprogramming in vivo is feasible and confers totipotency features absent in standard iPS or ES cells.

Stem cells: Reprogramming in situ
Alejandro De Los Angeles
Nature 502, 309–310 (17 October 2013)
http://www.nature.com/nature/journal/v502/n7471/full/nature12559.html

Cellular reprogramming to a stem-cell state has now been achieved in tissues of genetically engineered mice.
This work signals a future for regenerative medicine in which tissue fates might be manipulated in living organisms.

Subject terms:
Stem cells
Biological techniques
Developmental biology