so as I said it is like more than three thousand years of history this this is us God and in Indian literature or the Hindu scripture it has been recorded as a mod Omega so the people who are infected they urinate or this urine is basically sweet and the anti and flies are really get attracted because of the sweetness I mean 200 and 250 BC Apollonius vmm from Memphis he's coined the term diabetes and that is to go through basically it's passing the water basically that's what it is and then later on the mellitus which is a word for the honey which is included into it and in 1500 BC over this sorry in a 150 BC people realized that it is only mainly associated among the women's and that's what you know the more and more knowledge has been developed in recent years the recently still 300 year back John Kohler documented excess of sugar in the blood and urine 1831 were not basically linked the diabetes to the glycogen metabolism than the in 1869 the Paul Legrand's basically Turman found this discovered islet cells in the pancreas islets of langerhans that's what it has been called after that in 1889 Joseph and Oscar basically created diabetes and dog by removing the pancreas and in 1910 the insulin you know it has been proposed the chemical which is involved in controlling the glucose in the blood so that's what the history about the diabetes and I mentioned few minutes back that diabetes is divided into three different classes mainly type 1 type 2 end just a little diabetes the number of people which are basically with these visas are you know 30.3 close to million people in United State itself so if you look at that number it is one out of 10 the people who have got the diabetes type 1 diabetes is an autoimmune disorder and it's result from the insulin dependence and commonly detected before the 30 years of age more than 18,000 youth are diagnosed each year and 5% of total diabetic population is type 1 diabetes basically type 2 diabetes it is a basically metabolic disorder and lack of insulin production all the insufficient use of the insulin and that's what result in type 2 diabetes commonly it is seen after the 40 years of age but nowadays you know the way our habits has been changing you see earlier than that and many of the diseases are like or increase recently more than 5,000 users are diagnosed each year and it account for more than 90% of the cases contribute to this type 2 diabetes in gestational diabetes which is like during the pregnancy it is sin and nobody knows the mechanism behind it but 3 to 5 percent of the pregnant human eu-us develop this diabetes it is a lifelong chronic disease basically and it is associated with multiple complication different organs are getting affected by this disease so for example the brain and cerebral circulation eyes you know you get the retinopathy basically you're the oral health is decreased your cardiac function is reduced your kidney functions which proper the peripheral nervous systems or your the lower limb sensation which affected and that ulcerative food that is the some of the main complications and to give the idea about you know how do you washing this this is is like everyday 3,800 Americans will diagnosed with diabetes out of 200 Americans go under the amp addition every day pretty much and 1:36 enter the stage of kidney disease which is really you know major problems and then more there are close to 2,000 develop severe retinopathy and the blindness which is developed so looking at this is a very you know complex and very life-threatening disease and obviously the cost associated with the disease and with the treatment is going to be are too much so in America we spend more than three hundred and twenty-two billion dollars for the treatment of the diabetes or taking care of the patients with the diabetes and which is like almost 30 percent of the Medicare which goes for the treatment of the diabetes and which is close to 20% of the money from the oral health care system is utilized in taking care of the diabetes so talking about all these stats and everything you know what we know and as I mentioned the type 1 diabetes is autoimmune disorders and it is one of the disease there are like more than 100 autoimmune disease there and now we know at least after 3,000 years in last 50 years we started understanding that there are multiple genes are associated with most of the autoimmune diseases there is imbalance in the immune system which contribute in the development of this autoimmune disorders and then the very important facts are the environmental factors and that's what one should really look into that is a pesticide fertilizers microbes virus bacteria and other industrial population pollutions which contribute in development of many of the autoimmune diseases the next line I'm going to show you you know the number of different genes in a world in the type 1 diabetes per to say so the pancreas is the organ which is mainly in oil in the diabetes and there are 20-plus different genes are altered or mutated and which directly contribute to the dis functioning of the insulin production then the immune system plays a very important role and there are more than 100 plus genes are really people have identified which are involved in development of type 1 diabetes so it is a very complex disease so there are lots of genes which are involved so you know people are thinking about that ok we can use a CRISPR technology or gene therapy can we fix all those different genes at a time so it is going to be a challenge so talking about that I'm going to take you know this is on this slide little bit extra time to just make you understand what exactly is going on with the diabetes so as I said that it is a genetic factors mainly plays a role and you have seen that number of genes which in all and you know we are not going to talk about each and every gene we cannot take that much of you know we don't have that much of time but I think I'm going to try and use this one so in normal circumstance you have enough islet cells in the body and the way the slide is divined that like what is happening in the periphery is shown in the top what is happening in the pancreatic lymphnodes and what is happening in the pancreas which is shown here so in normal circumstance of islet cells in the pancreas which are there something happened with respect to genetic factors with respect to environmental trigger where the viruses malaysians you know we are nowadays we have the so many of the pesticides and different fertilizers which we are using all that somehow contribute in terms of you know somehow altering the u.s. islet cells the interferon alpha which goes I mean this is I'm trying to simplify the nature don't work that way just keep in that mind that nature is more complex and as a we scientists we try to simplify everything and make it more complicated but anyway talking about that we and that there are certain things happens and as a result the eyelets your own cells start calling the administration saying that we are foreigners or something like that as a result you know the and at the same time somehow there is there are the cells which really suppresses the Ottoman disorder by the they are called the T regulatory t-cells basically so their population start going down somehow around the time the cells islets are showing that we are foreigners somehow you know they they they behave weirdly as a result there's the cd8 T cells which are the killer cells they come inside and they start killing you are the islet cells during this process you know more antigens are get processed and presented by dendritic cells and the cd4 cells comes in to the feature which is a helper cells which is a important part of the you are a human system and that leads to the development of the B cell clone which are going to produce the auto antibodies against the insulin as well as a different islet cells which are there different time and we will talk about that also shortly when this whole process happens and then you are producing more antibodies you are killing more of the your own islet cells and then as a reason all the time the production of the insulin start going down going down and here are some little bit of the honeymoon phase and the style changes with different people and as a result over the time you are going to have less amount of the islet cells which are going to produce the incident which is a key component in your metabolic things so the point you have to remember from this light this something happens and the T helper T cell imbalance occurs and there are four major component of the helper T cells which th1 cells th 2 cells th17 and t reg cells and was that happened at the same time and these are the other than the T helper cells other company of the immune system also goes out of the control and all that result in the destruction of the u islet cells basically so in this slide I'm just going to know what is this penguin and what is this I'll it says basically so everybody now know that ok the when the pancreatic function is impaired so less amount of the insulin is going to be produced and the islet cells are consists of basically your the main our beta cells alpha cell delta cells and gamma cells and these cells produces more important hormones basically insulin and a myelin by the beta cells alpha cells produces a glucagon Delta cells produces somatostatin and gamma cells are polypeptides and all these hormones are really important in terms of metabolism and how the what we eat food is process and get absorbed by the different part of the body and out of that the insulin is really the key component of the system so and that's what we just initially identified that that's the molecule which is yet impaired so what we know about so so insulin is a very important molecule and it is involved in regulating more than hundreds of genes in the body it is involved in the uptake of the glucose for example a very simple and which is the key component of your you know activity of the body it involved it's a pretty late the glycolysis it in all in glycogen synthesis protein synthesis uptake of the ions which is potassium ion the waste on which you are the cardiac functions and many other muscular activities are going on insulin is involved in controlling or they in negatively or inhibiting the glycol neurogenesis gluconeogenesis glycogenolysis lipolysis ketogenesis so it is a very important molecule involved in the metabolism basically that's what the main thing you guys should remember and you can look into what are the different things are really affected so what is the treatment for that everybody knows that the insulin is missing in type diabetes so the treatment obviously for the type 1 diabetes is going to be the insulin so is there cure there is no cure for the type 1 diabetes right now so what are the things you can control you can keep on checking your the level of the glucose in the circulation you take the insulin you monitor your milling van right now and do the regular exercise that's what the options which is there with the type 1 diabetes basically and this molecule which is as I mentioned it's discovered in 1921 it is consists of alpha and beta chain or a and B chain it has got three disulfides two disulfides in the e allow a chain and then their other a and B chains are connected by the by the disulfide bonds there are different kind of analogs which are available right now to take care of the diabetes so start acting rapid-acting you know the the one which are like long lasting so based on that and nowadays you can have the different kind of the treatment so insulin is there people have done lots of studies to getting more insulin and then there are the pumps which has been developed also to inject the insulin so talking about the pump you know in 1963 the first pump which has been developed by there are now carriage and you can see that the the size of that insulin pump people used to you know have that time and then over the time it is really developed so much that recently the pumps are like less than your credit card size basically overall so that kind of the development which has happened Medtronic is doing I know great work with respect to the development of the pump so with respect to this device and for the treatment of the type one diabetes there's a lot of things which are going on I'm just going to take minute or two to talk about type 2 diabetes and treatment options which are available so type 2 diabetes as I told you it is like develop because we do less exercise we sit in front of the computer for a long time and that is one of the main culprit second thing is that the kind of food we what we eat you know the right now I was just watching you know everybody was eating too much of the pizza and I iced I really you know did bad things to my health by eating the pizza I used to eat 70% of my lunch and Dina used to be pizza and I'm not you know said don't eat it but you know everything in balance is really the important thing and then eating on time is really another important thing I will tell everybody sleeping on time is really important thing and these are the basic things we start missing and then we use too much of the pesticide we use too much cleanliness is also not good sometimes that's balance is required everywhere nowadays we use this the stroller Isis right sanitizers you know and you know how many people really think about you know those sanitizers so we they claim that we kill 99.9% bacterias what happened to that point one person anybody think about that you know anybody think about that we kill 99% you know know those bacterias are competing with each other so think about that if you remove that you know that competition now the one which has survived which are the really the bad one because they are the resistant to what you are using and now you remove the competition for them so what is going to happen you know it is like simple logic things you know as I know that we do a great job in advertisement and we get the carried away with it but we have to think you know out of the box always logically that what we are doing is right or not okay but coming back to the type 2 diabetes so once we identify okay there is a step 1 is that diagnosis ok you know that okay there is a problem so first thing doctor always going to say let's change the lifestyle you know do the exercise regular exercise and in metformin is a common drug which is given but if with that if the a1c is not control and it goes above a 1 C is basically amount of the glucose accumulate on your RBC's or your in the different you know proteins which are there so once that is happened that way and then you are to go with more therapies basically then in the I know you add two more drugs like your metformin will appear and there are the additional drugs which are the sulfide release kind of the drugs which will be there if that also don't work then you go with a med forming along with a bit insulin basically and then there is a start to basically in which you have the more the drugs which people have identified and you can use those and then if nothing controlled still then the main thing is that you go on and try to change the lifestyle how the metformin and then the intensive insulin therapy that's what only the option remain and our next slide this is the six different classes of the drug which is used for the type to try bleach treatment and I'm going to share this some of the slides so one can you know look into it I'm not going to spend but what is okay the limitation of current therapies is obviously the glycemic control so you have to break every day to look at you know how much blood glucose is there and then the idea is because you have to keep on you know taking this insulin injection we have the finite body space and how many injection are me every day one has to take like three to four injections and think about it that is really painful kind of the time so these are the main kind of the caviar or the of the limitation of these therapies as well as the or else you know integrates of the type 2 diabetes it is a chronic disease so every the patient has to take every day three times or four times of spills and which is really you know the ideal ends become the problem another limitation of this therapy insulin therapy is the define you have to fine-tune the glucose you know there and that's very important thing if too much of the glucose in the body is bad 2 liters is also bad because you will go into coma so you have to have that violence so you have to monitor it frequently risk of severe hyperglycemia and the main thing with respect to insulin therapy is that you miss the C peptide which is like you know if you look at the insulin the way it is it is a pro incident-free Pro insulin and then C peptide and initially people did not thought that the C peptide is important but now they started realizing that is also very important component and when we give insulin we agreement process insulin next important thing is that when we give in you know insulin we give only insulin we are not looking at other hormones which are missing like somatostatin glucagon in a polypeptide there are so many other things which are required and which are missing in type 1 diabetes so these are the main limitation of the insulin therapy and no doubt I'm you know now that pumps the people are developing they can pump the insulin as well as the glucagon simultaneously but still these are in the initial phases many of those things so next part of the topic talk is going to be on the organ transplant and cell based therapies what people are now developing and I'm going to you know talk you know just show you this slide to look at the complication which are associated so the people like small molecule like aspirin I look at them as like a bicycle it's a very simple kind of device next thing is like insulins which are like a no biological molecule but they are on five to ten thousand darkins in range and they are like you know the car you can say then there are the non biologics which are complex like your the heparin molecule low molecular beauty parent and all those those are like you know kind of the helicopter or something like that and monoclonal antibodies which comes into the picture which are like you know jumbo jets which are highly complex and then we are entering into the phase of this nanotechnology and cell based therapies according to me they're complex like in galaxies you know where is the universe and when we look at like organ agenices or the encapsulated cells that is further more complex and we cannot understand our planet itself so how do we can you know think about that complex things Multi was kind of the thing so those are the complication associated but still we have to work to find a good treatment and one of the thing you know early on people decided okay the organ transplant you know you if the pancreas is the problem can why not we transplant the pancreas and it's a good option and really it shows a very good cure eighty three percent of the people show very good in a control in the glucose levels however the limitation obviously shortage of donors how many you know donors are available and that is the main problem and then the second thing is that because you are putting the somebody's else spankers into the patient no human system is going to act against it so that is the reason your put the patient on the immunosuppressive therapy and that is a lifelong once again so these are the main problems associated with that and to do the organ transplant you know Penn College is very you know delicate kind of the organ and there are a lot of things associated you know transporting that organ from one place to another so people started thinking you know you stop doing the complete organ transplant can we take out the islet cells and put it into the body to take care of the insulin production and that's what early on in almost like this is also going on for last twenty five year plus and it is a obviously it is very instead of the using whole organ it is a non-invasive it is the less expensive way it's supposed to be and it is it is basically you can culture the islet cells in vitro people there are some people say you can prolly you can expand but it is not really possible to expand that very well and another important transportation and storage and all those things become easier and another important thing you should remember that Eureka you get all the alpha cells beta cells says whatever is required you can get it and then put it into the patient so these are the Edmonton protocol which is commonly known as and I just developed in Canada and multiple patients has gone through it so this is a simple thing from the donor you get the pancreas you process it and there is a recorded chamber which is where you digest the pancreas to get the islet cells and once you purify the islet cells by using the scope and everything the spirit for islets then you know put in the culture and then they are put into the back into the patient who is on immunosuppressive therapies there is a one second of limitation everybody can understand it is a source you know how many karevik sources are available and then there are the immunosuppressive therapies has their own drawbacks and their own limitations so but there is a really good success story associated with that Minton protocol in the early 2003 I think that's what it is yeah you can see that there is not too much of the control in the on the y-axis you are looking at you know beta cell insulin secretion basically capacity not too much it's secreted over the time because the process is not that very well developed but recently if you look at that from 2008 to 2012 you can see there is a really nice amount of insulin production so the isolation product process and transplantation has really improvise over the time and this basically is leads to the new new concept of using the stem cell therapy for the treatment of the type 1 diabetes so because of the there is a limitation of my amount of pancreas available from the human so one can really use a stem cells and or the genome islets and produce more amount of the islets for the transplantation but there are the challenges which are associated with all these both the therapies like using the stem cells as well as the xeno islets basically so advantages this advantage advantages is availability very easily to isolate and expand but with respect to the your stencils it is a difficult to differentiate them in the proper way like the you require alpha cells beta cells Delta cells gamma cells can you be able to do that and it is possible over the time it is going to be happening but right now there is a limitation with respect as you know eyelet where you can take the PO sign you know you can have as many as eyelets from the PO sign and the post on insulin is very close to the human insulin so that's the reason people are looking into that disadvantages still the growing the islet cells from the stem cells you know it's expensive because of the growth media and everything and that is controllable over the time you know that price can go down in case of the Zeno islets it's expensive because you have to grow that big into the clean environment and that is going to be the really expensive stuff because to grow the big into the clean environment it caused you know per peak like more than one hundred hundred and fifteen thousand dollars then in case of the stem cells the limitation is we know you may still get the beta cells you don't get Alpha Delta and other components in case of the Geno obviously all the subsets will be present their safety you with respect to stem cells people worry about immunogenicity which is very poor sign they are not but immunogenicity is going to be yes and no you can mo genetically modify and reduce the immunogenicity for the stem cells same thing can be applied to the pool sign but obviously it is a Geno genic project product so you are going to have the more unique responses safety with respected Geno viruses with the pol sign so there is going to be a you know more Geno viruses issues and obviously there are the ethical issues because some people will not like you know to go in through the Sinai lattice at the same time sell products some people don't like it okay I'm very close so let's let's go through couple of you know so one of the things keep in mind that you now require all the different cells upset basically I'm just going to go away from this one also so one can use this now the islet cells and one of the important caveat you're using the islet cells from this Zeno or the stem cells is the immune cells or immune system look at as a foreign thing so you have to isolate them from the immune system and one of the technique people are using is encapsulation technology so you encapsulate the islets and so that your T's your the human system will not go and attack it the antibodies cannot penetrate to destroy those islet cells and at the same time the nutrient can go inside oxygen can go inside and this device or these micro devices or micro encapsulation secret the insulin out and that's what which is really the goal of many of the people and then obviously you can genetically engineer the cells and overcome them in responses so there are lots of different companies who are working on encapsulation technology and we are one of the technically who is developing this encapsulation technology so our technology is like we take the Poussin islet cells we encapsulated using the chemical called as a alginate and we have identified the molecules which can keep the immune system at the bay and that's what our idea is that so they aim is simple that the cells will produce the insulin and that will be continuously delivered in the body and in the control fashion and obviously it will be used for the type 1 diabetes so this if we capsid molecule which I was talking about so that molecule is involved in attracting the T regulatory cells at the transplant site its block the CTL attacked it can increase the angiogenesis or track the stem cells suppresses the why you know why maintain formations and it can inhibit the foreign body reactions basically and that is what I know and one can I did there are the molecule available in our body itself like eyes pancreas testes or is this the human privilege organ they do secrete some proteins which keep the immune system at the base the image system cannot attack those organs basically so we identify some of those molecules which can be used in this encapsulating material and which can be routed over the time to keep this no islet cells protected another important thing one has to keep in mind that I let sell themselves are the immuno protect they have the human privilege kind of the capacity so they can secrete themselves immuno immuno protective molecule so if you can maintain the health of those islet cells they can create the environment around them to keep them in a healthy condition so our product how many minutes I have 10 minutes right so our product is like we are you know take the neonatal poster the peak isolate get the pancreas then prepare you know means they do the collagenous digestion and then remove the debris and culture to get rid of the ice in our cells and other cell type and just by simple culturing process enrich the islet cells population once that is enriched by day six we go and encapsulate them by using the Buchi quipment basically and once those are encapsulated once again we culture them so that they can mature and because this whole process itself is a stress inducing so always you ought to think about that if it is something which has gone through the stress it is going to be not in a good health it's not going to be going to able to protect itself from the immune system attacks so you have to culture it for some time once it is come to the normal state now you can put it in back into the body and here you know in the preliminary product we are planning to put it into O Mendte which is one of the major organ in the body and that's what our idea of doing it but to do all this thing you know you require the very good quality you know healthy Peaks basically which are grown in the clean environment you require the GMP be like you know solely processing encapsulation technology you know how to have the preclinical data and that's what we are working on right now and then you know you go into the clinical trial if you have the time I'm not I will go through this slide and then the couple of next slide will just omit it so to develop any of the product you how to optimize you know like in our case there is a recaps in the molecule which keep the immune system at the bay so we have to optimize the concentration how much it should be released what can we release candidate what are the different molecules we can use which has got more half-life or the better half-life so we have to optimize that you have to optimize the isolation of the in neonatal post on islet so you we have looked at age of the piglet strain and source of the piglet the enzymes which used to digest the pancreatic islet cells culture conditions so there are a lot many things when I have to go through it and then once you isolate and you have to do the encapsulation so in encapsulation you know you have to identify different alginates which is a based one you have to optimize that process of I know encapsulation what how does that molecule is going to affect that we caps in that the release of those cytokines or the immunomodulator molecule and how good those encapsulating agent is involving exchange of the waste product and a nutrient how does the glucose is crossing over how the insulin is coming out and glucagon so so you have to do lots of different things before you develop the good product and that's where you spend more time in developing and any drug development like small molecule drug development take 8 to 12 years to from the start to the finish from the rnd to the clinical trial where the biologics are going to take a little bit longer than that you know so it is very anywhere between 8 to 15 years once you just start developing it so I'm just going to you know skip this slide and skip the slide so just to give you the idea I know no doubt that we can clear this micro eyelids now micro eyelids once you put it inside these are the gino product or the eyelid suppose in the case of the emergency if you have to remove all that product out you need some way to remove it and that's the reason people are thinking about developing macro pouch or the system by which you can keep this micro capsule inside there another pouch and in case of the images you can able to remove it so one of the project we are working on is decelerate organs one can use it and the pancreas you know from the different spaces you can use and that do help the islet cells to grow efficiently and one can use those kind of the pouches to put this micro capsule inside and then put inside the patient and that can work as a good pouch and that is one of the long-term kind of the thing currently we are working with another company called as a so NOAA company where you know if you know the Edmonton protocol you get the islet cells and put it into the lever and hoping then the lever will produce the insulin basically that's all the idea but that doesn't work over the time because over the time the amines get a a system get activated and they start killing as well as you lose the both the function of the lever as well as of the islet cells so here the the approach we are taking is that cell power system so you can clear it initially to the patient you create the pouch you know which can get vascularized once that portion is get vascular as properly now you can put micro eyelets or a micro encapsulated eyelets into that that's what the approach you know some people are trying to develop so talking about all this thing you know whatever the future is leading to and everybody remember this slide that there are the genes immune system and environment and if I asked you guys one quick question you know what you think will be the best you know what you we can control out of this all this three component very easily or efficiently things the environment right at least to begin with so I think we have to work toward that you know and young you young people you how to you know think on that how do we can take care of the environment the amount of the plastic we are putting in the sea is like I think I heard that two billion tons per year and that is scary and that is he is going to come and you know bite back us you know it is that's how the nature whatever you throw to the nature is nature is going to throw back to us so so please you know that's some of the thing if we can control in our hand that's will be the important thing but once again coming back to the self-weight serie series what we want we want a therapy or we want the devices or something which can produce which can have all this four component of the islet cells alpha cells beta cell gamma delta at the same time we can able to put them in the body where it will be properly get vascularized because if it is not going to get vascularized they are not going to get the proper nutrient if they don't get new trend they are not going to survive for the long time but obviously at the same time the insulin has to sense and it's sure a new glucose actually be cells instrument has to be secreted out so the west polarization is very important thing another thing which you know either we signed this very forgetting is the gnosis neuronal system so if you know it's really one has to think about that insulin is secreted just by the thinking about the food and that means there is something else which is happening and how do we can improvise that neuronal you know innervations basically so the when the islet we implant it can they have the proper neuronal stimulus going on and then the important thing is that how we balance the immune system and there are the multiple ways people are working like party cell therapies you know regulatory cells to develop so it is going to be next you know i will save in next 10 years there is a good possibility that we will have the device you know which we can put it and we can able to cure at least diabetes in in terms of the time you know this is the one slide which talk of where we are the pancreas transplantation yes it is potential cure and it shows 83 percent success rate but that is not going to be standard of choice because we don't have that many you know donors available islet transplantation yes it is a potential and it's an experimental stage a lot of things are going on stem cell transplantation potential treatment artificial pancreas devices lot of things going on you know people are now producing those devices which can secrete the insulin glucagon somatostatin and then the C peptide and all that and then the xenotransplantation is another approach because many groups are working on it which can you know take care of it so I just take home a message for all of you you know so always you know this is a story I always liked about it it is from the one of the sect called Mahanagar sect which is about blind people you know trying to see how the elephant looks like and I know the people who was touching the trunk they feel that he is like snake the people who are touching his year they feel like he's like you know some kind of you know big cloth piece you know the people who are try you know they are feeling that he's like some kind of the sharp object and so on and so on basically so I want you guys you know to be not like you know that way but go beyond you know see the complete elephant always and another thing I always like to tell about a bee I like that book and and I hope you guys read the rigor mortis book the rigor mortis book by the Richard Harris but how sloppy science create a worthless cures crushes hopes and wished billions it is one of the nice book whenever you get time you know it's it's really important to read about and I think the you young people are going to be the you know key for the success so so please don't be like those blind you know guys look at everything with the open eye and you know that's all thank you know if you have any questions I will try and answer if not I will you know give ya know you know I don't make Edmonton protocol you know you have to you know see that they one of the main problem is that when you do this transplant in case of the Edmonton protocol also all the time because you your immune system still acting very strongly and that initial process itself our surgical process create the instantaneous blood reactions against those transplanted and they die so whether you have to do multiple transplant is not like once you do it it's done for it and that's the reason you have to develop this macro devices or something by which you can easily pull the cells inside and every six month or every you know one year you can able to remove them and put it new cells so which is going to be their future it has it as the alginate basically don't allow you know it I will not say completely blocks the antibodies to go across we have done some of the studies and it takes more than like I will say 48 hours to penetrate antibodies but see just penetrating the antibody is not you require the complementary factors also going along with that and complete the caption is providing like main thing is that when you put these capsules inside microcapsules the foreign body reactions which start happening and then the macrophages and which becomes a gigantic you know cells and they start covering that the capsules so over the time now you are cleared and you and that's how the immune system or the body whenever the foreign thing is put inside they create the cover on that and that's how basically that whole thing is block but the V capsule is not allowed to grow anything on those micro capsules and that's how it remain always a porous in nature so it can keep on you know that things get going if without a recaps in you see the nice kind of the thin membrane form or and then over the time it's become thicker and thicker so I guess you overcome those kind of the issues with the V capture really see that what we put inside is lasts only for 72 hours but we found that if you keep this eyelid healthy they themselves can produce these molecules and they keep on secret so it we can see that the main point is in many of this cell based therapies you can you keep these cells happy and healthy in the first phase and that's where many of the things which are failing that we put down whatever the cells inside the body when we do the surgical process itself that itself cleared in kilometer reactions you know if you can somehow avoid that or somehow reduce that impact you know and once they remain healthy there for some time many of the stem cells many of the islet cells are going to produce themselves the proteins which can keep the immune system and the bay but that's the tricky thing you know and the way sorry go ahead no I was talking about the way the embryo you know take care of many of the things it is a foreign thing which is growing there for nine months but without you know anything it can raise so nature has really developed many of the things we have to just understand we identified many molecules when I was working at one of the cell taxes company which is incubator of the Georgia Tech and we identified multiple proteins which is secreted from the testes or he Orion cancers eyes you know which can keep the immune system at the bay and we have to you know there is a way we can do it I think over the time are you planning to use 500 capsules of what is the size of a past the size that's a really good question right now the size of our cap suits is around 600 micron which is really a big you know we have to you know there is a way the technology is coming up where you can have the citizens the the eyelid itself are 150 to 350 400 micron in size so you can have a very thin layer like 2 to 3 say that you don't require cell to cell contact and if one can create that very thin layer that's true it is but that is going to be on of the challenge you cannot go to this micro capillaries and all that you can use as I know say the thing is that these are the pancreas extracellular matrix do help the islets to remain healthy and there is some kind of the communication which goes from that post thing it will make sense but as a proper kind of the vasculature I really don't know whether it will really work or one has to use a 3d you know printing kind of database that you create those and then those you know you created the device and they can be put inside and remote okay