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| 1 | CRGchannel | ENG - Cellular reprogramming: a real tool of regenerative medicine? - ... | 1024 | 6 | 45.4 | 15:01 | so it's very important to in the general public to make science because this is uh increase awareness about what we do in the lab first of all and increase sensibility to fund research and then of course people understand much more what is science about so that we are trying of course to to find solution but not all I do believe that to bring science in the general public uh is the mission of a scientist so we do not have only to stay in the lab but also to make this uh available to to everybody this in the long run we push politician to put more funding and and not only politician but also company and uh any foundation that can fund science if is something that goes from one cell to an adult so one cell can divide and give rise to two cell this one cell is very toy poent divide and give rise to two cells then eight cells and to um the Mora and the blastos from the blastos that is 3.5 days and AR to an embryo which is formed from three different tissue which has called or mesoderm endoderm and ectoderm this little mass of cell which is called Inner Cell mass and this group of cells basically give rise to embryonic stem cells we in the lab can isolate embrionic stem cell from this group of cells that derive from an embryo 3.5 days post Fertilization in a mouse or 5 days in a human so these cells are very toy poent so they can generate each tissue of the body body they can be propagating indefinitely and they can differentiate in each cell of our body differentiation is when you take a stem cells and this stem cell can give rise to arthrite lymphocyte muscle cell or neurons any cells but this process that seems very easy is very tightly regulated normally what you have is that from a stem cell you have another stem cell that is called a progenitor cell or adult stem cell so for example an adult stem cell of the nervous tissue can give rise to neuron olenite or asites for example the lineage development of the of the mattic system start from an another stem cell that is called hematopoetic stem cell and this as you can see in these slides can give rise to a plora of different progenitor cells this cells here can differentiate in the cells that is called CNP and CNP can differentiate in M or GMP and so on but the interesting things that I want to point you out is that at each branch in the end can give rise to this cell line or this cell line so mcroof or ainop but it cannot give rise for example to rroy there are other stem cells that are multipot that is different to be toy poent because they can differentiate in some cells and not in others you can have adult St cell in the brain in the heart in the bone marrow that can give rise to specific cells of that particular tissue this is what is differentiation is a stepbystep process that an a cells that is a stem cell become more and more committed until it becomes a differentiated cell these cells they beat as as the hair a stem cell that we have IND used to differentiate in a cardom myosite in the differentiation is something unidirectionally from a stem cell you can go to a muscle cell to a fiberblast to a cardom myosite you can go to a fiberblast that is a skin cells and and then you can go back to a stem cell and then you can differentiate again this cell in another lineage so this is was really a change of the paradigma I mean up to last century it was thought that differentiation was unidirectionally but this is wrong so reprogramming is when you go back from a somatic cells to a stem cell is an increase in poy or the differentiation and therefore I mean we know very little about we don't know if it or in nure and the moment as I said is a a a technical laboratory to produce uh let's say stem cell from somatic cell one of the very early experiments demonstrate that the fate of a somatic cell can be reversed back to a stem cell phenotype and this was through nuclear transfer you can transfer the nucleus in a a nucleated orite what happens is that this you generate a clone so the nucleus of the different a cells is completely back to a stem cell phenotype but can also generate several clone animals so in this way we have changed the fate of the nucleus of a somatic cells and make possible that this new entity the Crone can generate a new organism there are others method one is that you can basically make an extract of stem cell or make an extract to all sides and then this you can basically put on somatic cell and this you can induce partially ear programming not stable but nevertheless you can induce some reprogramming also by this method another method that is through Cell fusion you can take a different differentiated cells and you can really fuse with a stem cell so then you have an hybrid here there was an experiment in in a lab from Dr Schuler they took uh the cytoplasm without the nucleus and this was fused with a somatic cell and in this case they did not get any reprogramming in contrast when they Fus the nucleus of the stem cell with the different cells they got reprogramming the factors that induce reprogram are in the nucleus of the stem cells and not in the cytoplasm of the stem cell you take this Gene and you put this gene into the nucleus of the somatic cell what you will have is that with a very few genes you can convert this cell into a stem cell like or what is called IPS this was the experiment of yamanaka they took a differentiated cell they expressed these four factors here through a virus and then they could generate an IPS cells that give rise to could be propagated like embryonic stem cells or or they could generate mice there is another method which is the lineage reprogramming you can make a direct conversion from one cell to another without passing through the pl poent state so this method have been identified specific factors which can do this conversion to conclude this part to wrap up what I said it was stood for a long time that these are all you know separated box from an emonic stem cell you can have ectoderm meod and anoderm what I told you really at the beginning and it was told that there was not possibly you know way of passing from one box to another but more recently with two different approach one is through self Fusion or through the expression of specific factors now we know that you can push differentiation back and you can really pass from one differen cell into into another now what we can do with this there are several applications or dream project and one of the dream project is that you can create IPS and you might might cure a sick organ so this is a dream project because it's really I mean we are very far to reach to this point we are studying the mechanism controlling reprogramming and so there are group of genes that in the balance between differentiation and and stemness they keep the maintain the stem phenotype there are group of genes that maintain the differentiated phenotype what we try to do we try to silence uh the genes that induce differentiation to keep the stemness phenotype these are the four factors that the Japanese uh researcher yamanaka used in his first experiment these are not essential so they can be substitute by other factor or by other modulating other pathway so they are all not essential at the moment the use of this IPS is in the clinic is not even in in the clinical trial phase you can find also these 10 top things to know about the stem cell treatment there are different type of stem cells there is not a universal stem cell therapy that will cure any types of disease or any type of conditions there are very few accepted uh stem cell therapy currently just because people say that stem cell help this does not means that they do why takes so long to uh to develop new therapy because science is going very slow when when you do a stem cell therapy you you have to instruct cells to become what you want they have to become as much as we manipulate in vitro in culture as much as we induce differentiation and therefore cells lose their potency and they likely is more complicated to handle and to let the cells to do what you wish uh they should do there are a lot of uh treatment for sale that are not um are very very risky also because clinical trial take a lot of steps to authorization to go really into the clinic nevertheless we do believe that stem cell science is an important field and and we hope that in the end we will really have something important for regenerative medicine we are mostly concentrated in self Fusion mediated reprogramming why because it's a very very efficient way to induce reprogramming we do believe that it might be a physiological mechanism Fusion is a process that occur normally during development it occurs during fertilization it occurs during the formation of a specific tissue in the placenta or during the formation of muscle of bone some people that believe that Fusion can be a mechanism to repair or regenerate a tissue and we are studing exactly this so what is regeneration first of all it's something that in the lower uh ukar like in fish or in amphibians it happens naturally and one example of this a particular uh frog is the salamander after the amputation these cells here they undergo the differentiation and then they redifferentiate again and in the end they form again the the Lim of course we don't have this ability to regenerate our hands if we have an amputation unfortunately but this means that during the evolution this is something that have been lost from lower ukar to higher ukar but can in a way be stimulated so we are trying exactly this to stimulate this process what we are doing in the lab and this our working hypothesis is that you if you have a damage somewhere in your body you can have some circulating Bomar cells that confuse with cells that have been damaged to make it easy is a signal that can activate the cells and tell the cells looks you are to become very potent and you have to activate this group of genes okay we do believe that there is a reprogramming of the hybrids that are generating after fusion and then finally a regeneration of the tissue we have done this in vitro and now we are using a lot this approach to to try to to regenerate or to cure or to enance uh regeneration in in several disease model what we believe is this schematized here research that things that can trans differentiate or become something different in other tissue or after Fusion can become something different but we do believe we do believe that a cell from the bom marrow fuse with a somatic cell and form these hybrids which then can be reprogrammed and regenerate uh tissue to conclude srael is a a painter of the Renaissance in Italy we do believe that reprogramming is like the zus that blows on the on the cells and these cells they can be regenerated as the Venus here represented and and we do believe that this painting represent a bit the process of reprogramming | ↗ |