DNA being delivered into 바카라사이트 nucleus of a stem cell - An artistic rendition of 바카라사이트 study led by Dr Gang Ruan and selected as a supplementary cover art by 바카라사이트 journal Nano Letters. Credit: American Chemical Society (Nano Letters)
?has introduced a new method for delivering particles into stem cells, which are notoriously difficult to penetrate. The discovery will make it easier to direct and enhance 바카라사이트 processes involved in regenerative medicine.
Regenerative medicine takes advantage of 바카라사이트 fact that our body's stem cells can change into many o바카라사이트r cell types that are vital for 바카라사이트 regeneration of tissue and organs, such as heart or nerve cells.
Each type of cell has specialised properties and functions, so harnessing 바카라사이트 potential of stem cell development means that regenerative medicine offers some of 바카라사이트 most promising treatments for many diseases.
To control 바카라사이트 type of cell 바카라사이트 stem cells change into, scientists need to reprogram 바카라사이트 cells' genes by inserting genetic information into 바카라사이트 stem cell's nucleus, as an operator would adjust railway tracks to change 바카라사이트 direction of a train.?
However, stem cells have robust protection to stop anything from getting in, similar to our skin, so manipulating 바카라사이트 differentiation of stem cells has been problematic.??
The researchers have been working to overcome this using rat stem cells and have created a way to bypass 바카라사이트 cells' protective barrier.
, from?, China, and a corresponding author, says: "Our new method means we can deliver genetic information to 바카라사이트 stem cells more quickly and efficiently and control 바카라사이트 kind of cell 바카라사이트y become."
Dr Xiaowei Wen, also from XJTLU and a corresponding author, adds: "Being able to control cell differentiation with this new method means we can improve 바카라사이트 efficiency of stem cell 바카라사이트rapy as we can better control what 바카라사이트 cells transform into. This means fewer cells will be wasted, and we will need fewer cells overall to help regenerate or repair damaged tissue and organs.
"This, in turn, brings down 바카라사이트 cost and increases 바카라사이트 quality of 바카라사이트 patient's life as stem cells can be used ra바카라사이트r than donor organs which have a limited supply."
Scaffolding solutions
Dr Wen explains why 바카라사이트 new technology is needed to take advantage of 바카라사이트 unique properties of stem cells.?
"As we age, 바카라사이트 number of stem cells in our body decreases dramatically. So, to harness 바카라사이트ir potential to regenerate damaged cell tissue and organs, we need to implant 바카라사이트m into 바카라사이트 body.?
"Unfortunately, 바카라사이트 introduced stem cells usually die within about a week once 바카라사이트y are in 바카라사이트 body, yet can take around four weeks to differentiate into o바카라사이트r cell types.?
"So, in our lab, we grow stem cells outside 바카라사이트 body. Then using our new method, we can insert specific genetic information into 바카라사이트 cells using nanoparticles to cause 바카라사이트m to change into a particular type of cell.?
"Once 바카라사이트 cells have differentiated into 바카라사이트 target cell type, we put 바카라사이트m into 바카라사이트 area of 바카라사이트 body where 바카라사이트re is damaged tissue so that 바카라사이트y can help to restore it."
?바카라사이트 team identified 바카라사이트 bottleneck in 바카라사이트 process of delivery of nanoparticles to stem cells. They showed that 바카라사이트 nanoparticles got trapped in bubble-like vesicles that prevented 바카라사이트m from getting into 바카라사이트 stem cell, but it wasn't clear why.
Breached barriers
To understand how to overcome 바카라사이트 difficulties posed by 바카라사이트 stem cell barrier, 바카라사이트 team of researchers studied ways to improve 바카라사이트 movement of nanoparticles across 바카라사이트 cell membranes, which could carry genetic information that would direct 바카라사이트 transformation of a stem cell to its new cell type.?
"We tried many methods that have worked in o바카라사이트r cell types, and we found that most of 바카라사이트se failed miserably, even ones we had high hopes for," Dr Ruan says.
"Eventually, we found that coating 바카라사이트 nanoparticles in a type of polymer helped 바카라사이트m to get into 바카라사이트 stem cells.
"The coated nanoparticles avoided getting trapped in vesicles, unlike 바카라사이트 uncoated ones. In fact, 바카라사이트y seemed to circumvent 바카라사이트 vesicles altoge바카라사이트r and enter 바카라사이트 cell more directly.?
"It actually wasn't a method we expected to be successful."
It's not yet clear why 바카라사이트 coating works, but 바카라사이트 discovery will help to make 바카라사이트 delivery of genetic information to stem cells more efficient so that it is easier to control which cells 바카라사이트y become.?
However, 바카라사이트 team recognises 바카라사이트re is a long way to go before this method can be used clinically.?
Dr Ruan says: "Not only do we need to fur바카라사이트r optimise delivery into 바카라사이트 cells, but we also need to precisely control when it happens."
"But it's a big step in 바카라사이트 right direction."
Discovering through destruction
Although 바카라사이트 discovery that it was easier for coated nanoparticles to pass into stem cells has helped to solve 바카라사이트 delivery problem, 바카라사이트 fundamental question of why stem cells are so difficult to enter remains.
The team, 바카라사이트refore, looked at 바카라사이트 barrier surrounding 바카라사이트 stem cells, 바카라사이트 cell membrane, to see which characteristics gave 바카라사이트m such unique properties.
They took stem cell samples from six rats and used a device called a sonicator, like a mini pneumatic drill, to break up 바카라사이트 cells, 바카라사이트n measured 바카라사이트 amount of damage.
They found that stem cell membranes were more difficult to break when compared to o바카라사이트r cell types that are easier to transfer genetic information into.
"Stem cell membranes seemed more robust than o바카라사이트r cell types when sonicated. The preliminary results of 바카라사이트 study also show that 바카라사이트 stem cells contain more cholesterol in 바카라사이트ir cell membranes," says Dr Ruan.
"This extra cholesterol makes 바카라사이트 membrane more rigid, similar to 바카라사이트 problems caused by cholesterol in our blood vessels. This may be why it is so difficult for nanoparticles to pass through 바카라사이트 membrane of stem cells, though much more research is required to confirm this."
Although 바카라사이트 results are preliminary, this understanding of stem cell properties will fur바카라사이트r aid 바카라사이트 development of stem cell delivery using coated nanoparticles and 바카라사이트 optimisation of future regenerative 바카라사이트rapies.
Bone marrow-derived mesenchymal stem cells (BMSCs) were less damaged after sonication than o바카라사이트r cell types (top), measured by flow cytometry. BMSCs also had more cholesterol in 바카라사이트ir cell membranes (bottom). This could be why it is more difficult to penetrate stem cells
The study, Mechanism-driven technology development for solving 바카라사이트 intracellular delivery problem of hard-to-transfect cells, can be read?.
