Underlying mechanisms of 3d tissue formation

If you want to build an organ, such as for transplant, you need to think in 3D.

Using stem cells, scientists for some time have been able to grow parts of organs in the lab, but that is a far cry from constructing an actual, fully-formed, functioning, three-dimensional organ.

For students of regenerative medicine and developmental biology, this is why understanding how cells bend and move to form organs and bodily tissue is a hot topic.

And now a team at Kyoto University's Institute for Frontier Life and Medical Sciences have gained new understanding into how cells undergoing mechanical strain create the spherical structure of the eye.

Publishing in Science Advances, the team has found that individual cells together form a primordial, cup-like structure -- an 'optic cup' -- by sensing mechanical forces resulting from the deformation of the entire tissue.

"In the past, we succeeded in making the optic cup by culturing embryonic stem -- ES -- cells. To form a sphere, the tissue needed to first protrude from primordial brain tissue and then invaginate inside," explains first author Satoru Okuda."But how individual cells sensed and modulated themselves to form that shape had been unclear."

The team developed a computational simulation that calculates the formation of three-dimensional tissue structures. Using this knowledge and past experimental data, they constructed a virtual precursor-eye and were able to predict the physics driving the sphere-forming cells.

Their findings show that during optic cup formation, a cell differentiation pattern -- pushing cells into the cup shape -- is generated, causing a portion of the cells to spontaneously fold into the tissue. This force caused by 'self-bending' propagates to the boundary region, where other cells sense the strain.

"The combination of the tissue deformation and the strain on the boundary of the optic cup generates a hinge that further pushes the bending cells," continues Okuda, "leading to the cup-like structure.The next step was to verify this prediction using actual ES cells."

Utilizing mouse ES cells in culture, the team applied mechanical strain on specific points and were pleased to detect the calcium responses, mechanical feedback, and cell shape changes they had predicted in the simulations.

These findings reveal a new role for mechanical forces in shaping organs, which is crucial in forming complex tissues, even in a petri dish. The team will continue to investigate these forces, seeking to continue advancing the field of regenerative medicine.

"While our research shows the possibility of controlling the shapes of organs made in vitro -- using appropriate mechanical stimulation based on prediction -- current techniques are still limited," concludes lead scientist Mototsugu Eiraku."We hope to improve the predictive accuracy of our simulations and recreate more complicated tissues and organs in the future." 

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . 

You can submit your abstract on Session or Track : 15. Regenerative Medicine

'Cellular dust' provides new hope for regenerative medicine

While stem cells have the most therapeutic potential, the benefits of regenerative medicine may best be mobilised using extracellular vesicles (EVs), also known in the past as "cellular dust." A team of researchers from CNRS, AP-HP, INSERM and Paris Descartes and Paris Diderot Universities have tested these vesicles for the first time in a porcine model for the treatment of post-operative digestive fistulas. Their results, which yielded a 100% success rate and open the door to testing in humans and broader possibilities for applications.

Extracellular vesicles are matter that is released by cells. Seen for many years as not having any value, this 'cellular dust' has been studied and presents therapeutic properties similar to their mother cells, without their disadvantages: These vesicles do not divide, limiting the risk of cancer, and do not differentiate either, thus preventing the development of poor function. Furthermore, it appears that they can be produced by a single donor for several patients, and have already demonstrated their therapeutic potential in animals in repairing heart, liver and kidney lesions.

In the case of digestive fistula, in which there is abnormal communication between organs in the digestive tract or with the skin, regenerative medicine is an important therapeutic avenue to explore. Fistulas of this kind respond poorly to current treatments; they can develop following post-operative complications or an auto-immune disorders such as Crohn's disease, which causes digestive tract dysfunction.

For the first time, scientists at the Matières et systèmes complexes Lab (CNRS/Université Paris Diderot), the Gastroenterology and Endoscopy Department at the Hôpital Européen Georges Pompidou (HEGP) AP-HP and the Laboratoire Imagerie de l'angiogénèse, plateforme d'imagerie du petit animal (INSERM/Université Paris Descartes/HEGP), used extracellular vesicles from stem cells to treat digestive fistula in a swine model. The study reveals that local injections into the fistula of a gel containing these vesicles results in the complete closure of post-operative digestive fistula.

Researchers intend to test the new approach in a perineal fistula model found in Crohn's disease, with the hope of replacing the vvv. The vesicle gel could be administered locally and easily and become a simpler, safer and more effective treatment.

We welcome researchers from different part of the world to submit your latest research at our upcoming conference “12th World Congress on Cell & Tissue Science” scheduled on March 11-12,2019 in Singapore which is mainly focuses on the complications the consequences of Stem Cell, Regenerative Medicine, Stem Cell Therapy, Cancer Cell Biology , Technical Advancements in cancer treatment and many more. For more info visit our conference website:Cell Tissue Science 2019

Researchers confine mature cells to turn them into stem cells

Stem cells are the blank slate on which all specialised cells in our bodies are built and they are the foundation for every organ and tissue in the body.

Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) and the FIRC Institute of Molecular Oncology (IFOM) in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

"Our breakthrough findings will usher in a new generation of stem cell technologies for tissue engineering and regenerative medicine that may overcome the negative effects of geonomic manipulation," said Prof Shivashankar.

Turning back the cellular clock

It has been over a decade since scientists first showed that mature cells can be reprogrammed in the lab to become pluripotent stem cells that are capable of being developed into any cell type in the body. In those early studies, researchers genetically modified mature cells by introducing external factors that reset the genomic programmes of the cells, essentially turning back the clock and returning them to an undifferentiated or unspecialised state. The resultant lab-made cells, known as induced pluripotent stem cells (iPSCs) can then be programmed into different cell types for use in tissue repair, drug discovery and even to grow new organs for transplant. Importantly, these cells did not need to be harvested from embryos.
Researchers has shown that mature cells can be reprogrammed, in vitro, into pluripotent stem cells without genetically modifying the mature cells, simply by confining the cells to a defined area for growth.

Resetting mature cells

When fibroblast cells were confined to rectangular areas, they quickly assumed the shape of the substrate. Based on previous work from the Shivashankar lab, this indicated that the cells were measuring and responding to the physical properties of their environment, and conveying this information to the nucleus where DNA packaging and genome programmes would adapt accordingly.
The team grew the cells over 10 days until they formed spherical clusters of cells. Genetic analysis of the cells within these clusters revealed that specific characteristics of chromatin normally associated with mature fibroblasts were lost by the sixth day. By the 10th day, the cells expressed genes normally associated with embryonic stem cells and iPSCs. The researchers have now learnt that by confining the mature cells for an extended period of time, mature fibroblasts can be turned into pluripotent stem cells.
To confirm that the fibroblasts had indeed been reprogrammed into stem cells, the researchers then directed their growth, with high efficiency, into two different specialised cell types. Some cells were also directed back into fibroblasts.

Stem cell technologies redefined

The physical parameters used in the study are reflective of the transient geometric constraints that cells can be exposed to in the body. For example, during development, the establishment of geometric patterns and niches are essential in the formation of functional tissues and organs. Similarly, when tissue is damaged, either through injury or disease, cells will experience sudden alterations to their environment. In each case, mature cells may revert back to a pluripotent, stem cell-like state, before being redeployed as specialised cells for the repair or maintenance of the tissue.

"While it is well established that confining stem cells to defined geometric patterns and substrate properties can direct their differentiation into specialised cells, this study shows for the first time that mechanical cues can reset the genomic programmes of mature cells and return them to a pluripotent state. The use of geometric constraints to reprogramme mature cells may better reflect the process occurring naturally within the body. More importantly, our findings allow researchers to generate stem cells from mature cells with high efficiency and without genetically modifying them." Prof Shivashankar explained.

Our conference Cell Tissue Science 2019, mainly focuses on the complications the consequences of  Cancer Cell Biology and Technical Advancements in cancer treatment. The speakers from different part of the world will be present their immense research talk on this specific topics. We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” .You can also present your latest research at our conference.For more info visit : Celltissue Science 2019