Three-dimensional graphene foam as a biocompatible and conductive scaffold for neural stem cells

[whatthe]

[URL]http://www.nature.com/srep/2013/130403/srep01604/full/srep01604.html?WT.mc_id=FBK_SciReports[/URL][QUOTE]The neural stem cells (NSCs) are a self-renewing and multipotent cell population in the central nervous system, which exhibit promising prospects in developing cell therapies for neural regeneration[SUP][URL="http://www.nature.com/srep/2013/130403/srep01604/full/srep01604.html#ref1"]1[/URL], [URL="http://www.nature.com/srep/2013/130403/srep01604/full/srep01604.html#ref2"]2[/URL][/SUP]. Constructing a microenvironment, a scaffold that regulates NSC behavior and tissue progression has been an essence in clinical applications[SUP][URL="http://www.nature.com/srep/2013/130403/srep01604/full/srep01604.html#ref3"]3[/URL][/SUP].[/QUOTE][QUOTE]One new trend of scaffold design is to create conductive platform that introduces external electrical stimuli to NSCs, since electrical stimulation can affect the migration, differentiation, and proliferation of neural stem cells[SUP][URL="http://www.nature.com/srep/2013/130403/srep01604/full/srep01604.html#ref12"]12[/URL], [URL="http://www.nature.com/srep/2013/130403/srep01604/full/srep01604.html#ref25"]25[/URL][/SUP]. Electrically conductivity of scaffold can be achieved by utilization of conductive polymers and carbon based materials which include carbon nanotubes (CNTs), graphite and graphene[SUP][URL="http://www.nature.com/srep/2013/130403/srep01604/full/srep01604.html#ref14"]14[/URL][/SUP].[/QUOTE]
I hardly know what this article entails, there is a lot to read but I think the gist is we can use graphene to form the framework for growing neural cells. AKA growing a or part of a brain.

Please somebody tell me what this means!

[Kazumi]

Good news, although there is still quite a hurdle to get the cultivated cells to actually work as intended. I'm going to try and explain them.

1. First off we have a problem that not all neurons look the same. There's unipolar, bipolar, pseudounipolar, and multipolar cells. These are the base categories of neurons, some of which are more common in certain areas than others. For example, Bipolar neurons participate in sensory processes.
[img]http://i.imgur.com/E4PFIoo.gif[/img]
Getting the right kind of cell in the right part of the brain is crucial, but it doesn't end there as you will see.

2. We also have the problem with cytoarchitectonics. The brain itself might look like one big grey lump of goo. But take a microscope and look closer and you will see that different areas has a different kind of cellular architecture. This german guy named Korbinian Brodmann sliced brains in ultra-thin layers and looked at through a microscope. Then he recorded the different cell compositions and made a map of the brain called Brodmann areas. The (lateral) map looks like this.
[img]http://i.imgur.com/ItkVhkT.jpg[/img]
So there's 52 areas in total in which cells are connected in different patterns, and on top of that there's a bunch of different kinds of cells. Things are getting tricky.

3. Alright, so we have started to grow the right kind of neuron in the right area. But as you might already know, neurons sends signals to other neurons. How many other neurons can one single neuron be connected to? Up to 3000! (don't quote me on this though, it's a vague memory I have from a lecture I had)
Again we face another problem with getting the right kind of thing in the right place. We have to get the cell to produce the right kind of neurotransmitter as well. Neurotransmitter is a chemical substance that is released at the very tip/end of the neuron called Axon Terminal. There are hundreds of different neurotransmitters, but most neurons can produce a couple of them. Most common are Glutamate and GABA. One neurotransmitter you might recognise is Dopamine. Dopamine is the main substance that is activated in the Substantia Nigra (part of the brain). Lack of dopamine production in that area is a known cause of parkinsons disease.

4. So, imagine if we somehow got all these things right. Are we done? I'm afraid not. In the brain there's more than just neurons. In fact, the brain contains far, far more Glial cells than "ordinary" neurons. What is a glia cell then? There are several kinds of glia and they serve different purposes. Astrocytes is the normal scaffolding this graphene aims to replace in transplants/stem cell growth. But astrocytes also make up the Blood Brain Barrier. A tiny wall that protects the neurons from infections that might be carried through the bloodstream. Microglia fucks up foreign bodies that might find itself in the wrong neighbourhood. Then we have the Oligodendrocytes. These fellas are kind of difficult. The purpose they serve is crucial, and if they are injured they won't regenerate or regrow. Oligodendrocytes envelop the axon (longest tendril from the neuron that actually carries the signal) in a sheet of myelin. Myelin is a lipid that helps insulate the axon so that the electrochemical signal doesn't leak. Lack of oligodendrocytes is known as Multiple Sclerosis. So without these, the transplanted neurons are virtually worthless.
[img]http://i.imgur.com/RaritpE.gif[/img]

I can take some questions, but please understand that I am but a mere student. It already feels like I'm at the deep end of the pool.

[Zeneros]

Graphene is crazy

[whatthe]

[QUOTE=Kazumi;40157197]Good news, although there is still quite a hurdle to get the cultivated cells to actually work as intended. I'm going to try and explain them.

1. First off we have a problem that not all neurons look the same. There's unipolar, bipolar, pseudounipolar, and multipolar cells. These are the base categories of neurons, some of which are more common in certain areas than others. For example, Bipolar neurons participate in sensory processes.

Getting the right kind of cell in the right part of the brain is crucial, but it doesn't end there as you will see.

2. We also have the problem with cytoarchitectonics. The brain itself might look like one big grey lump of goo. But take a microscope and look closer and you will see that different areas has a different kind of cellular architecture. This german guy named Korbinian Brodmann sliced brains in ultra-thin layers and looked at through a microscope. Then he recorded the different cell compositions and made a map of the brain called Brodmann areas. The (lateral) map looks like this.

So there's 52 areas in total in which cells are connected in different patterns, and on top of that there's a bunch of different kinds of cells. Things are getting tricky.

3. Alright, so we have started to grow the right kind of neuron in the right area. But as you might already know, neurons sends signals to other neurons. How many other neurons can one single neuron be connected to? Up to 3000! (don't quote me on this though, it's a vague memory I have from a lecture I had)
Again we face another problem with getting the right kind of thing in the right place. We have to get the cell to produce the right kind of neurotransmitter as well. Neurotransmitter is a chemical substance that is released at the very tip/end of the neuron called Axon Terminal. There are hundreds of different neurotransmitters, but most neurons can produce a couple of them. Most common are Glutamate and GABA. One neurotransmitter you might recognise is Dopamine. Dopamine is the main substance that is activated in the Substantia Nigra (part of the brain). Lack of dopamine production in that area is a known cause of parkinsons disease.

4. So, imagine if we somehow got all these things right. Are we done? I'm afraid not. In the brain there's more than just neurons. In fact, the brain contains far, far more Glial cells than "ordinary" neurons. What is a glia cell then? There are several kinds of glia and they serve different purposes. Astrocytes is the normal scaffolding this graphene aims to replace in transplants/stem cell growth. But astrocytes also make up the Blood Brain Barrier. A tiny wall that protects the neurons from infections that might be carried through the bloodstream. Microglia fucks up foreign bodies that might find itself in the wrong neighbourhood. Then we have the Oligodendrocytes. These fellas are kind of difficult. The purpose they serve is crucial, and if they are injured they won't regenerate or regrow. Oligodendrocytes envelop the axon (longest tendril from the neuron that actually carries the signal) in a sheet of myelin. Myelin is a lipid that helps insulate the axon so that the electrochemical signal doesn't leak. Lack of oligodendrocytes is known as Multiple Sclerosis. So without these, the transplanted neurons are virtually worthless.

I can take some questions, but please understand that I am but a mere student. It already feels like I'm at the deep end of the pool.[/QUOTE]

First of all, thank-you!

I don't really have many questions probably because I don't understand this all very well...

So where does the main, or current problem lay?
1. In the replication/construction of the different types of neurons?
2. Piecing it together properly, like before the advent of this graphene skeleton?
3. Are we basically creating "cosmetically" (for lack of better word) similar cell structures that do not function as intended?

edit

I think I missunderstood the part the graphene plays in this. Is it there to act as some sort of bridge/axon for the grown nueral cells?

[dass]

[QUOTE=Zeneros;40157417]Graphene is crazy[/QUOTE]

The NANOMACHINES of the real world.

[Kazumi]

[QUOTE=whatthe;40157718]First of all, thank-you!

I don't really have many questions probably because I don't understand this all very well...

So where does the main, or current problem lay?
1. In the replication/construction of the different types of neurons?
2. Piecing it together properly, like before the advent of this graphene skeleton?
3. Are we basically creating "cosmetically" (for lack of better word) similar cell structures that do not function as intended?

edit

I think I missunderstood the part the graphene plays in this. Is it there to act as some sort of bridge/axon for the grown nueral cells?[/QUOTE]

I remember talking to my professor about this and she said that the main problem is to make the neurons work as intended. There's already been several experiments regarding neural transplants. But getting the neurons to grow and extend its tendrils/axons/dendrites to create the right pathways is a completely different story. She mentioned that transplanted/cultivated tissue is extremely hard to connect and make it respond to signals/produce signals of its own, even if it is a perfectly healthy neuron. So I guess #3 on your list is most relevant today.

I do have some trouble understanding the details of the article. At first I thought it was a simple framework/scaffold, much like astrocytes, simulating a natural environment for the cells to grow in. But then I read something about the response of electrical stimulation and direct biocompatibility. Maybe it actually works both as astrocytes and as an axon? I'm a bit sceptic about that last part though, since I'm not sure how the postsynaptic (receiving) neuron would differentiate between a excitatory and inhibitory signal.
You remember the mass connectivity I mentioned above? ~3000 neurons linked to each cell. Some of them produce excitatory neurotransmitter, such as Glutamate. When glutamate binds to the receiving neuron it often triggers a signal impulse. There's also the opposite. When a neuron binds the neurotransmitter GABA (gamma-Aminobutyric acid), it holds the signal back and won't fire for a short while.

I've made some previous comments in news threads regarding brains. [URL=http://facepunch.com/showthread.php?t=1232646&p=38820364&viewfull=1#post38820364]This particular post[/URL] I made was another one regarding transplantation. I also made [URL=http://facepunch.com/showthread.php?t=1236467&p=39048726&viewfull=1#post39048726]this one about alzheimers[/URL]. I try to put a lot of energy to keep things clear and understandable. I love the things I study so evidently I also like to share. The brain is an incredibly fascinating and scary piece of meat.

[Mr. Bleak]

Kazumi voted for resident neuroscientist.

Seriously though, that's some really interesting stuff. Hopefully after working away the complexities one by one, all these problems will be solved and science can move forward into solving some issues of the brain.

It's really cool to imagine that purely through evolution we have things like brains that are way more complex than anything that humanity can make, despite coming from a response to change rather than a concentrated effort to make something new.

[whatthe]

[QUOTE=Kazumi;40158116]I remember talking to my professor about this and she said that the main problem is to make the neurons work as intended. There's already been several experiments regarding neural transplants. But getting the neurons to grow and extend its tendrils/axons/dendrites to create the right pathways is a completely different story. She mentioned that transplanted/cultivated tissue is extremely hard to connect and make it respond to signals/produce signals of its own, even if it is a perfectly healthy neuron. So I guess #3 on your list is most relevant today.

I do have some trouble understanding the details of the article. At first I thought it was a simple framework/scaffold, much like astrocytes, simulating a natural environment for the cells to grow in. But then I read something about the response of electrical stimulation and direct biocompatibility. Maybe it actually works both as astrocytes and as an axon? I'm a bit sceptic about that last part though, since I'm not sure how the postsynaptic (receiving) neuron would differentiate between a excitatory and inhibitory signal.
You remember the mass connectivity I mentioned above? ~3000 neurons linked to each cell. Some of them produce excitatory neurotransmitter, such as Glutamate. When glutamate binds to the receiving neuron it often triggers a signal impulse. There's also the opposite. When a neuron binds the neurotransmitter GABA (gamma-Aminobutyric acid), it holds the signal back and won't fire for a short while.

I've made some previous comments in news threads regarding brains. [URL=http://facepunch.com/showthread.php?t=1232646&p=38820364&viewfull=1#post38820364]This particular post[/URL] I made was another one regarding transplantation. I also made [URL=http://facepunch.com/showthread.php?t=1236467&p=39048726&viewfull=1#post39048726]this one about alzheimers[/URL]. I try to put a lot of energy to keep things clear and understandable. I love the things I study so evidently I also like to share. The brain is an incredibly fascinating and scary piece of meat.[/QUOTE]

I want to ask you a few questions leading to a bigger questions, but the pace would be too slow in a thread, so can I add you on steam?

But the overriding question I want to ask, in case you can answer it is this:

Can we somehow get the grown cells to interact with other grown cells with artificial stimulation using the neurotransmitters we know of, say for niche circumstances for people who lack productivity of Dopamine we could get the neurons pumping, then connect them to the existing brain? Although now that I think about it, the basics of that question seems to be no different from attempting to straight up inject some into a patient.

Or does it appear like every brain is so unique that it is seemingly impossible to make a "multi platform" specimen? Kind of like the formatting differences between Windows and Linux, for example.

[Kazumi]

Yeah, I do believe you can, and to some length it is already being done today. In the case of severe parkinson cases there can be artificial electrical activation through a process called Deep Brain Stimulation. Basically you send tiny jolts of electricity to help kickstart the signals in the Mesostriatal pathway (which help regulate voluntary movements).

I wouldn't say it is impossible for a multi-purpose specimen. Though I do believe we have quite a long way to go.

Sure, you can add me to steam if you want.