WEBVTT 1 00:00:10.100 --> 00:00:14.900 The first question will be what type of diabetes can potentially benefit 2 00:00:14.900 --> 00:00:20.200 from stem cell therapy? Yeah, so fundamentally when we look at diabetes 3 00:00:20.600 --> 00:00:23.700 as all of us know, when clinicians working in the field of 4 00:00:23.700 --> 00:00:27.400 diabetes, we very well know a very broad categorization of diabetes is 5 00:00:27.400 --> 00:00:30.600 type one versus type two diabetes, right? Of course, it's a very 6 00:00:30.600 --> 00:00:33.700 limited model that we are looking at. We know there are various 7 00:00:33.700 --> 00:00:37.800 other subtypes of diabetes which classically did not fit into the clear-cut 8 00:00:37.800 --> 00:00:40.100 picture of type one or type two diabetes, but for the sake 9 00:00:40.100 --> 00:00:43.100 of understanding and for the sake of clarity and for the sake 10 00:00:43.100 --> 00:00:46.500 of trying to see, you know, how these stem cells can benefit 11 00:00:46.500 --> 00:00:50.500 such you know diabetes per se, we can broadly category categorize it 12 00:00:50.500 --> 00:00:54.100 as type one and type two diabetes. Now looking at it, I 13 00:00:54.100 --> 00:00:57.900 would say stem cell therapy can benefit you know type one as 14 00:00:57.900 --> 00:01:02.400 well as type two diabetes. Now how is the question here? So 15 00:01:02.400 --> 00:01:06.800 what we need to understand is that the pathogenesis, the etiopathogenesis of 16 00:01:06.800 --> 00:01:10.500 type one versus type two diabetes is unique, is different, right? They 17 00:01:10.500 --> 00:01:14.700 do not or they for mostly they do not have an overlapping 18 00:01:14.700 --> 00:01:18.100 you know zone to a great extent, but of course there may 19 00:01:18.100 --> 00:01:20.700 be certain areas where they might be a certain degree of overlap, 20 00:01:20.700 --> 00:01:25.600 but fundamentally the etiopathogenesis of both the conditions remain unique. So for 21 00:01:25.600 --> 00:01:29.800 both these conditions, I would say there's a lot of promising research 22 00:01:29.900 --> 00:01:34.400 which shows early phase clinical trials have shown promise to address both 23 00:01:34.400 --> 00:01:39.300 these conditions you know in terms of getting better and better outcomes 24 00:01:39.500 --> 00:01:44.500 fundamentally in three primary parameters or three primary metrics 25 00:01:44.500 --> 00:01:47.000 is what we are looking at that is reduction of HP even 26 00:01:47.000 --> 00:01:51.300 C, improvement in the C peptides. Please understand C peptide is a 27 00:01:51.300 --> 00:01:55.700 marker of the pancreatic health, right? So especially in type one diabetes 28 00:01:55.700 --> 00:01:59.200 when the pancreas is failing, when the C peptide is declining, we 29 00:01:59.200 --> 00:02:04.500 know that the pancreatic health is getting more poor, right? So HbA1c 30 00:02:04.500 --> 00:02:08.400 is one, improvement in C peptide is one and of course improvement 31 00:02:08.400 --> 00:02:10.800 in the fasting blood glucose. These are I would say the gold 32 00:02:10.800 --> 00:02:14.800 standard which a lot of the initial clinical trials have looked into, 33 00:02:14.800 --> 00:02:17.000 you know, the initial data that we have. Of course, we don't 34 00:02:17.000 --> 00:02:21.900 have studies which have involved a large you know patient population per 35 00:02:21.900 --> 00:02:25.400 se, but with the limited early clinical trials that we have, I 36 00:02:25.400 --> 00:02:29.000 would say the trial results look very promising for type one diabetes 37 00:02:29.000 --> 00:02:34.100 as well as type two diabetes, right? So the specifics of that 38 00:02:34.200 --> 00:02:37.000 we can come into the subsequent questions or if you want me 39 00:02:37.000 --> 00:02:39.600 to highlight it here, we can do that also in terms of 40 00:02:39.600 --> 00:02:43.300 how stem cells have been shown to be beneficial for type one 41 00:02:43.400 --> 00:02:46.600 versus type two diabetes. Would you want me to elicit it here 42 00:02:46.600 --> 00:02:48.700 or would you like to take it up in a further question? 43 00:02:49.400 --> 00:02:53.800 Sir, absolutely because you are already discussing about it, we would love 44 00:02:53.800 --> 00:02:59.000 to hear that first. Sure, sure. So in type one diabetes, what 45 00:02:59.000 --> 00:03:03.300 is the pathogenesis behind type type one diabetes? As clinicians we very 46 00:03:03.300 --> 00:03:08.300 well know the fundamental problem is the problem of autoimmunity. Our own 47 00:03:08.300 --> 00:03:13.100 body immune cells attacking the pancreatic cells, isn't it? That's the fundamental 48 00:03:13.100 --> 00:03:17.800 problem in type one diabetes. So what is the outcome of that? 49 00:03:17.900 --> 00:03:21.800 Most people who are diagnosed with type one diabetes, you know, the 50 00:03:21.800 --> 00:03:25.400 fundamental problem is that the challenge here is they are the beta 51 00:03:25.400 --> 00:03:28.400 cell population has been destroyed to a very great extent. There may 52 00:03:28.400 --> 00:03:31.500 be other cells also which have gone abnormal, but fundamentally we look 53 00:03:31.500 --> 00:03:34.600 into the beta cell function. That's why we look into see how 54 00:03:34.600 --> 00:03:37.100 much is the C peptide when a person is being diagnosed with 55 00:03:37.100 --> 00:03:42.200 type one diabetes, right? Because fundamentally it's the problem of autoimmunity damaging 56 00:03:42.200 --> 00:03:47.300 the pancreatic cells. So here how do MSC therapy, 57 00:03:47.300 --> 00:03:50.800 stem cell therapy, MSC is mesenchymal stem cells, right? How do stem 58 00:03:50.800 --> 00:03:55.200 cells particularly help in terms of type one diabetes? So I would 59 00:03:55.200 --> 00:03:59.400 say in type one diabetes, the role of MSC therapy. See MSC 60 00:03:59.400 --> 00:04:03.000 is one category of stem cells we are talking about, the mesenchymal 61 00:04:03.000 --> 00:04:07.000 stem cells. There are various other categories of stem cells, right, which 62 00:04:07.000 --> 00:04:12.200 have recently gained gained a lot of popularity, especially the iPSC 63 00:04:12.200 --> 00:04:17.200 cells, induced pluripotent stem cell. This is a wonderful niche 64 00:04:17.200 --> 00:04:20.200 of stem cells that we have you know recently discovered in the 65 00:04:20.200 --> 00:04:24.100 last few years you know by a few colleagues from Japan and 66 00:04:24.100 --> 00:04:27.700 it has shown to be of immense promise, right? as the term 67 00:04:27.700 --> 00:04:33.000 suggest these are called induced pluripotent stem cells. That is the fundamental 68 00:04:33.000 --> 00:04:38.100 principle is this. We take our own adult differentiated cells. We 69 00:04:38.100 --> 00:04:41.400 induce it. We tell the cell hey go back to your initial 70 00:04:41.400 --> 00:04:45.700 state you know before you differentiated into another cell through certain through 71 00:04:45.700 --> 00:04:49.200 certain markers, through certain cues we tell them to go back to 72 00:04:49.200 --> 00:04:52.300 their initial state. And then we tell them hey you need to 73 00:04:52.300 --> 00:04:56.900 become this tissue, you need to become pancreatic beta cells, right? So 74 00:04:57.600 --> 00:05:01.900 you know I would say in type one diabetes, this particularly particular 75 00:05:01.900 --> 00:05:06.200 category of cells called induced pluripotent stem cells, iPSC stem cells have 76 00:05:06.200 --> 00:05:10.600 shown a lot of thoughts, right? that is recently there was a 77 00:05:11.200 --> 00:05:13.500 you know it came in the news. It was quite popular in 78 00:05:13.500 --> 00:05:16.500 the last few year maybe last few months ago for the first 79 00:05:16.500 --> 00:05:20.400 time we have been able to actually have you know induced pluripotent 80 00:05:20.400 --> 00:05:23.100 stem cells. we have been able to implant it in the anterior 81 00:05:23.100 --> 00:05:26.800 abdominal wall and we have been able to achieve insulin independence for 82 00:05:26.800 --> 00:05:29.500 these patients. That is that we have been able to stop insulin 83 00:05:29.500 --> 00:05:33.800 therapy for this type one diabetes patient. And the patient continues to 84 00:05:33.800 --> 00:05:37.400 be insulin free the post one and a half two years, right? 85 00:05:37.400 --> 00:05:41.500 post the post the therapy that the patient underwent. So this is 86 00:05:41.500 --> 00:05:44.700 one of the prime examples of how we can use our own 87 00:05:45.000 --> 00:05:50.000 body cells to actually differentiate into the pancreatic beta cells, right? 88 00:05:50.200 --> 00:05:53.400 They continue to produce insulin and they take over the function of 89 00:05:53.400 --> 00:05:58.000 the pancreatic beta cells, right? So this is a very promising area. 90 00:05:58.200 --> 00:06:02.600 We are actually able to utilize these cells to generate insulin. They 91 00:06:02.600 --> 00:06:06.000 take over the role of the beta cell, right? So of course 92 00:06:06.000 --> 00:06:09.300 lot more work needs to be done here because the problem in 93 00:06:09.300 --> 00:06:13.500 type one diabetes is the active autoimmunity that continues to destroy the 94 00:06:13.500 --> 00:06:17.200 pancreas. So we still need to do a lot more research to 95 00:06:17.200 --> 00:06:22.700 see what can be done to prolong that insulin independence for 96 00:06:22.700 --> 00:06:26.400 the period of time. So with respect to type one diabetes, I 97 00:06:26.400 --> 00:06:29.800 would say the induced pluripotent stem cells have shown a lot of 98 00:06:29.800 --> 00:06:33.600 promise. There are certain limitations which we can discuss in the coming 99 00:06:33.800 --> 00:06:37.800 few minutes. So as far as type two diabetes, diabetes type two 100 00:06:37.800 --> 00:06:42.000 diabetes is concerned, it's a little different condition. The etiopathogenesis is different. 101 00:06:42.000 --> 00:06:47.200 It's mainly because of glucotoxicity, high inflammation in the body, right? The 102 00:06:47.200 --> 00:06:51.900 obesity, the insulin resistance, that is the etiopathogenesis in type two diabetes. 103 00:06:52.500 --> 00:06:55.100 So here we are not too much worried about the poor beta 104 00:06:55.100 --> 00:06:58.900 cell reserve. We are more concerned about these other factors. So there 105 00:06:59.000 --> 00:07:02.800 I would say MSC therapy has shown quite a good promise, the 106 00:07:02.800 --> 00:07:08.400 mesenchymal stem cell therapy. What is the advantage of MSC therapy? Right? 107 00:07:08.700 --> 00:07:13.300 In fact, in recent times, MSC cells have been renamed as medicine 108 00:07:13.300 --> 00:07:18.200 signaling cells, MSC. Why? It is because it has been found out 109 00:07:18.200 --> 00:07:23.700 that these cells have the property of actually having a medicinal effect, 110 00:07:23.800 --> 00:07:27.500 that is through their paracrine action. They're able to send out molecules 111 00:07:28.000 --> 00:07:32.400 which positively influence the niche around them, the environment around them and 112 00:07:32.500 --> 00:07:35.700 induce repair in the cells around them. That's the beauty of these 113 00:07:35.700 --> 00:07:39.800 MSC cells. So there's a lot of evidence which shows for type 114 00:07:39.800 --> 00:07:45.100 two diabetes when patients have undergone a series of MSC therapy 115 00:07:45.100 --> 00:07:48.600 infusions over a period of time. We are able to improve the 116 00:07:49.100 --> 00:07:53.000 diabetes numbers in terms of HbA1c, in terms of improvement in C 117 00:07:53.000 --> 00:07:57.400 peptide, in terms of improvement in the fasting blood sugar levels. So 118 00:07:57.400 --> 00:08:00.700 of course there may be there are studies which do compare using 119 00:08:00.700 --> 00:08:05.200 MSC therapy for type one diabetes also, but I would say fundamentally 120 00:08:05.200 --> 00:08:09.200 when I look at the scientific principle behind it, you know, it 121 00:08:09.200 --> 00:08:13.000 makes clear sense to me that we need to use cells which 122 00:08:13.000 --> 00:08:16.000 actually are able to regenerate into the pancreatic cells. And that 's 123 00:08:16.000 --> 00:08:20.300 where iPSC cells, induced pluripotent stem cells can have this benefit more 124 00:08:20.300 --> 00:08:23.400 than MSC cells, right? So this is a I would say an 125 00:08:23.400 --> 00:08:28.100 overview of how stem cell therapy can be useful for type one 126 00:08:28.200 --> 00:08:34.200 as well as for type two diabetes. Yeah. All 127 00:08:34.200 --> 00:08:39.500 right, sir. Sir, since you were already discussing about the limitations, 128 00:08:39.800 --> 00:08:43.500 so the next question is about that only. What are the current 129 00:08:43.500 --> 00:08:48.200 limitations of insulin therapy that stem cells aim to overcome? Over to 130 00:08:48.200 --> 00:08:51.800 you sir. Yeah, yeah, that's a very good question, right? So what 131 00:08:51.800 --> 00:08:56.400 are the limitations of insulin therapy? Let's try to understand them. See 132 00:08:56.400 --> 00:08:59.500 the in limitations of insulin therapy are fundamentally what? You need to 133 00:08:59.500 --> 00:09:03.000 take the pricks. Is it isn't it? You ask any patient, especially 134 00:09:03.000 --> 00:09:07.100 a type one diabetes child, you ask how distressed the child is, 135 00:09:07.100 --> 00:09:10.600 the parents are. They need to take multiple shots of insulin every 136 00:09:10.600 --> 00:09:15.600 day. And it's a basal bolus regimen which is given multiple pricks 137 00:09:15.700 --> 00:09:19.100 of insulin daily. Along with that, you need to do glucometer checks 138 00:09:19.100 --> 00:09:22.100 of the blood sugars multiple times in a day. Can you imagine 139 00:09:22.100 --> 00:09:27.100 the pain and difficulty with that process? So fundamentally the problem you 140 00:09:27.100 --> 00:09:31.500 know with insulin therapy is the pricks, the pain. Any form of 141 00:09:31.500 --> 00:09:35.000 pain will definitely reduce the quality of life. This is not that 142 00:09:35.000 --> 00:09:38.300 it's a very painful process. It's not that with the modern insulin 143 00:09:38.300 --> 00:09:42.700 pens, the pain and discomfort is much less, right? But still it 144 00:09:42.700 --> 00:09:46.500 is not a comfortable act, right? We always as human beings, we 145 00:09:46.500 --> 00:09:49.200 want to go with acts which give us pleasure, right? We are 146 00:09:49.600 --> 00:09:53.000 our brain system, reward system is looking for pleasurable acts. We are 147 00:09:53.000 --> 00:09:57.100 always we tend our behavior is oriented towards that, right? We want 148 00:09:57.100 --> 00:10:00.700 to avoid pain, but if we have a practice like this, unfortunately 149 00:10:00.700 --> 00:10:04.500 that hits the quality of life of these patients. So fundamental problem 150 00:10:04.500 --> 00:10:09.500 with insulin, although insulin is life saving, insulin therapy is life 151 00:10:09.500 --> 00:10:12.500 saving for type one diabetes. Please don't get me wrong. You know 152 00:10:12.500 --> 00:10:15.600 after the discovery of insulin, we have been able to save the 153 00:10:15.600 --> 00:10:19.800 lives of type one diabetes patients in a dramatic fashion, you know 154 00:10:19.800 --> 00:10:23.600 probably to the extent of non-diabetic individuals also we have been able 155 00:10:23.600 --> 00:10:26.900 to extend the life, but the quality of life gets impacted with 156 00:10:26.900 --> 00:10:31.900 insulin therapy, right? That's the problem. So here one of the greatest 157 00:10:31.900 --> 00:10:35.400 advantages let's say in the coming years, if we are able to 158 00:10:35.400 --> 00:10:39.900 come to a phase where we are able to you know regenerate 159 00:10:40.000 --> 00:10:43.500 the beta cells you know in a very efficient manner so that 160 00:10:43.500 --> 00:10:46.300 we can transplant it. See there is already a lot of work 161 00:10:46.300 --> 00:10:50.200 which is being done on islets of transplantation. Adult islet cells are 162 00:10:50.200 --> 00:10:53.800 transplanted into the type one diabetes patient, but it is failing because 163 00:10:54.100 --> 00:10:57.800 the autoimmunity comes in, the cells are not viable, we are not 164 00:10:57.800 --> 00:11:01.700 able to achieve insulin independence for these patients or maybe for a 165 00:11:01.700 --> 00:11:04.000 short time, yes, but then they have to be back on insulin. 166 00:11:04.600 --> 00:11:08.900 So that's a problem, right? So if in the near future as 167 00:11:08.900 --> 00:11:12.900 research progresses, if you are able to increase the insulin independence time, 168 00:11:13.400 --> 00:11:16.800 if you are able to come to a phase where these cells 169 00:11:16.800 --> 00:11:20.300 are able to differentiate into the adult pancreatic beta cells and that 170 00:11:20.300 --> 00:11:25.200 continues for a longer longer period, the cells remain viable, that's going 171 00:11:25.200 --> 00:11:28.600 to be a life-changing milestone. That's going to be a scientific discovery 172 00:11:28.600 --> 00:11:32.000 which is going to stay, right? That's what we are all working 173 00:11:32.000 --> 00:11:34.600 towards. We want to come to that phase where we are able 174 00:11:34.600 --> 00:11:39.100 to achieve that the cells which are able to achieve insulin independence 175 00:11:39.100 --> 00:11:41.700 for a prolonged period of time. We are on the right path. 176 00:11:42.100 --> 00:11:45.400 A lot of good work which is happening, right? And I think 177 00:11:45.400 --> 00:11:48.100 we as we go ahead, we need to advance the work further 178 00:11:48.100 --> 00:11:53.200 so that we are able to achieve the viable cells which regenerate 179 00:11:53.200 --> 00:11:55.900 into beta cells, the stem cells which regenerate into beta cells and 180 00:11:55.900 --> 00:11:59.400 they stay viable, right? We have been able to come to a 181 00:11:59.400 --> 00:12:04.400 phase where we can develop the pancreatic cells. The problem is viability. 182 00:12:04.400 --> 00:12:07.000 We are not able to keep them viable. So that's where the 183 00:12:07.000 --> 00:12:10.400 research needs to be focused where these cells continue to be viable 184 00:12:10.400 --> 00:12:14.400 and they continue to produce insulin. Second problem in type one diabetes 185 00:12:14.600 --> 00:12:19.000 is the autoimmunity. So even though you achieve good numbers of pancreatic 186 00:12:19.000 --> 00:12:22.500 beta cells, you know we are able to regenerate it, the autoimmunity 187 00:12:22.500 --> 00:12:26.600 continues to cause problem. On one side we are having you're regenerating 188 00:12:26.600 --> 00:12:29.700 the cells, you're implanting it. On the other side, the autoimmunity is 189 00:12:29.700 --> 00:12:33.100 continuously causing damage. So that has to be looked into. How do 190 00:12:33.100 --> 00:12:37.200 we prevent the autoimmune attack? Right? There's like a lot of research 191 00:12:37.200 --> 00:12:40.400 we can look into that in the coming questions. So that's where 192 00:12:40.400 --> 00:12:43.700 this research is headed. So fundamentally I would say this is the 193 00:12:43.700 --> 00:12:46.500 greatest advantage with stem cell therapy in the coming years and this 194 00:12:46.500 --> 00:12:50.600 becomes successful. We can be insulin independent for the patients. They don't 195 00:12:50.600 --> 00:12:54.500 need to be on multiple pricks in a day. The quality of 196 00:12:54.500 --> 00:12:59.100 life takes a dramatic impact through that, right? That's what we are 197 00:12:59.100 --> 00:13:03.300 looking forward to. And of course even another problem is of course 198 00:13:03.300 --> 00:13:06.900 with the insulin therapy for type one diabetes. I'm focusing on type 199 00:13:06.900 --> 00:13:10.200 one diabetes here because insulin is a primary therapy for type one 200 00:13:10.200 --> 00:13:14.200 diabetes. Type two diabetes, of course oral medications are there. So but 201 00:13:14.200 --> 00:13:18.200 insulin therapy another problem is in spite of having basal bolus regimen 202 00:13:18.200 --> 00:13:23.400 etc. for type one diabetes, we still fall short of having optimal 203 00:13:23.600 --> 00:13:27.200 sugar control, what we call glycemic variability still continues to be a 204 00:13:27.200 --> 00:13:31.100 problem. It is for type one diabetes patients. We still find challenges 205 00:13:31.100 --> 00:13:34.700 where the sugar goes extremely high and low. To keep the sugars 206 00:13:34.700 --> 00:13:39.100 within a range continues to be a challenge. So in spite of 207 00:13:39.100 --> 00:13:43.100 all the insulin, the newer insulin regimens etc. the newer types of 208 00:13:43.100 --> 00:13:45.900 insulin with this continues to be a challenge. So if we are 209 00:13:45.900 --> 00:13:49.300 able to have a system where that own native cells, the stem 210 00:13:49.300 --> 00:13:54.100 cells are able to produce insulin by differentiating into beta cells and 211 00:13:54.100 --> 00:13:57.700 we are able to have that as a standard therapy, right? I 212 00:13:57.700 --> 00:14:02.200 would say that's a far more superior treatment intervention compared to insulin 213 00:14:02.200 --> 00:14:05.600 therapy. But you know that's I would say that means a lot 214 00:14:05.600 --> 00:14:08.700 of work. We are going in the right direction, but much more 215 00:14:08.700 --> 00:14:11.800 work has to be done in this area. But the problem the 216 00:14:11.800 --> 00:14:14.600 future looks good in terms of where we are headed towards, right? 217 00:14:14.600 --> 00:14:19.700 So I'm quite happy with that. Yeah. That was very elaborate 218 00:14:19.700 --> 00:14:23.600 and insightful, sir. Sir, moving on to the next question that is 219 00:14:23.600 --> 00:14:28.600 what is the process of differentiating stem cells into insulin-producing 220 00:14:28.600 --> 00:14:34.300 beta cells? Yeah, so this is basically a lab process. 221 00:14:34.400 --> 00:14:38.700 It's more of the bench you know research that we are that 222 00:14:38.700 --> 00:14:42.800 we are discussing right now. How do researchers basically convert or differentiate 223 00:14:42.800 --> 00:14:46.000 it into adult beta cells? Of course, that's not my niche, basically 224 00:14:46.000 --> 00:14:51.100 a translational clinician. I I I I want to apply the 225 00:14:51.300 --> 00:14:54.300 basic signs to my patients. That's what I work towards, but of 226 00:14:54.300 --> 00:14:58.800 course fundamentally there is certain aspects involved which I can elucidate here. 227 00:14:59.400 --> 00:15:03.500 So how do these cells regenerate into beta cells? So like I 228 00:15:03.500 --> 00:15:08.500 said before, the challenge with using MSCs, so what 229 00:15:08.500 --> 00:15:10.800 are the different types of stem cells that are commonly used? One 230 00:15:10.800 --> 00:15:15.900 is the mesenchymal stem cells, second is you know the pluripotent 231 00:15:15.900 --> 00:15:20.400 stem cells. See mesenchymal stem cells are not pluripotent, they're multipotent because 232 00:15:20.600 --> 00:15:25.200 they fundamentally they are able to differentiate only into mesenchymal cells, mesoderm, 233 00:15:25.300 --> 00:15:29.700 right? But pluripotent stem cells are those which can differentiate to cells 234 00:15:29.700 --> 00:15:34.300 of any lineage, right? For example, the embryonic stem cells, right? But 235 00:15:34.300 --> 00:15:38.000 they have their own challenges. Embryonic stem cells unfortunately is a very 236 00:15:38.000 --> 00:15:42.600 ethical issue. We cannot use embryonic cells you know for research. It's 237 00:15:42.600 --> 00:15:45.400 like you know you're aborting the fetus, right? When you're taking out 238 00:15:45.400 --> 00:15:50.400 the embryonic cells. So that's not a viable option. So of course 239 00:15:50.400 --> 00:15:55.000 I would say post Yamanaka and the team from Japan were able 240 00:15:55.000 --> 00:15:59.900 to discover induced pluripotent stem cells. It's a revolution because here what 241 00:15:59.900 --> 00:16:04.300 is being fundamentally done is we take the adult cell. For example, 242 00:16:04.700 --> 00:16:08.100 a commonly used cell is the skin fibroblast. We take the skin 243 00:16:08.100 --> 00:16:13.100 fibroblast. We put in we induce certain factors. We transfect it 244 00:16:13.100 --> 00:16:16.600 with certain with certain vectors which give the cue to the genetic 245 00:16:16.600 --> 00:16:21.800 material that hey you need to go back into the primordial state, 246 00:16:21.900 --> 00:16:25.800 to the initial state, into the embryonic state where you initially started 247 00:16:25.800 --> 00:16:30.000 with. That's the message with these these vectors are able to convey 248 00:16:30.000 --> 00:16:32.400 to the genetic code. Now of course there's a lot of scientific 249 00:16:32.400 --> 00:16:36.900 steps involved. What are the what are the markers that are used? 250 00:16:37.200 --> 00:16:39.600 I don't think that's of key importance here. We need to understand 251 00:16:39.600 --> 00:16:43.200 the process involved in it. So once that happens, once they go 252 00:16:43.200 --> 00:16:47.100 back into the native embryonic state, then you have the flexibility. You 253 00:16:47.100 --> 00:16:48.400 have your you have come back to a state where the cells 254 00:16:49.900 --> 00:16:51.700 are open for many options. You want to differentiate those cells into 255 00:16:54.100 --> 00:16:57.900 pancreatic beta cells. Yes, you could do that. If you want that 256 00:16:57.900 --> 00:17:01.100 to develop into some other you know bone cells, yes, you could 257 00:17:01.200 --> 00:17:01.200 do that. Any form of cells or if you want to do 258 00:17:04.600 --> 00:17:07.900 that for cardiac cells, you could do that. So you have taken 259 00:17:07.900 --> 00:17:13.200 them back to the initial state, you know the undifferentiated pristine state, 260 00:17:13.300 --> 00:17:16.100 you know. They're taking those cells back. You know we have told 261 00:17:16.600 --> 00:17:18.600 you have given the cues for them to go back to that 262 00:17:18.600 --> 00:17:22.100 state. Now it's up to you what kind of markers you give 263 00:17:22.100 --> 00:17:25.600 to that cell gives that cell the direction to which it wants 264 00:17:25.600 --> 00:17:29.100 to go. For example, if you give markers like exendin four is 265 00:17:29.100 --> 00:17:32.200 one of those markers which tell the cells hey you need to 266 00:17:32.200 --> 00:17:37.500 develop into a pancreatic beta cell tissue, right? So once that happens, 267 00:17:37.500 --> 00:17:40.800 once you do the process of giving those markers again and giving 268 00:17:40.800 --> 00:17:45.900 the cue, please understand stem cells are beautiful cells that work with 269 00:17:45.900 --> 00:17:50.100 the signaling cues around the cell. Like what signals is the cell 270 00:17:50.100 --> 00:17:54.200 looking for? What is around it? That's where it starts going towards, 271 00:17:54.300 --> 00:17:57.800 right? So imagine when you're born, when you're a clump of embryonic 272 00:17:57.800 --> 00:18:00.800 cells, you know you don't have any of the organs, you don't 273 00:18:00.800 --> 00:18:04.600 have any of the adult tissue. You're just a ball of cells 274 00:18:04.600 --> 00:18:09.600 having life. The beauty of it is as the organogenesis starts in 275 00:18:09.600 --> 00:18:13.200 the womb, as you as the fetus starts growing, it is all 276 00:18:13.200 --> 00:18:16.500 the cue in the environment which tells the cells to which organ 277 00:18:16.500 --> 00:18:20.600 tissue to develop, right? That's the nature's gift. You're telling the cell, 278 00:18:20.800 --> 00:18:24.500 the tissue population to differentiate in their particular organ in the internal. 279 00:18:24.600 --> 00:18:27.600 It's all dependent on the niche in which the cells are found 280 00:18:27.700 --> 00:18:31.300 and the environmental cues. So the same thing is happening here. You 281 00:18:31.500 --> 00:18:34.400 artificially you give the cues for these cells to tell them hey 282 00:18:34.400 --> 00:18:37.800 you need to develop into beta cell tissues. Like as a certain 283 00:18:37.800 --> 00:18:41.200 markers like exendin four and other markers are used for this process, 284 00:18:41.300 --> 00:18:43.300 but that's not the goal here. We are not trying to make 285 00:18:43.300 --> 00:18:48.000 it very dry discussion here with a lot of these scientific molecular 286 00:18:48.000 --> 00:18:51.800 names. I'm just trying to give you the scientific picture of how 287 00:18:51.800 --> 00:18:55.100 it happens. So once the cue have is given to those cells, 288 00:18:55.200 --> 00:19:00.500 the cells start differentiating into the adult cell. Here in this instance, 289 00:19:00.700 --> 00:19:05.000 the beta cell of the pancreas, the insulin producing cells. So of 290 00:19:05.000 --> 00:19:07.800 course this is done in a in vitro process too. You have 291 00:19:07.800 --> 00:19:11.800 to do this outside in the lab where you're giving those cues 292 00:19:11.800 --> 00:19:15.900 to those cells. And once they start differentiating into the adult beta 293 00:19:15.900 --> 00:19:19.000 cells, you know you look at certain markers on those cells, the 294 00:19:19.000 --> 00:19:21.500 CD markers etc. and they tell you what is the kind of 295 00:19:21.500 --> 00:19:24.800 tissue right now. Once you know it is differentiated to the adult 296 00:19:24.800 --> 00:19:28.800 tissue, now's the chance where you can implant it, right? You can 297 00:19:28.800 --> 00:19:32.500 implant it into the body at viable sites. That word is very 298 00:19:32.500 --> 00:19:38.000 important, viable sites because the problem with these differentiated 299 00:19:38.200 --> 00:19:41.200 cells at this point is unless you have a viable site, it 300 00:19:41.200 --> 00:19:45.500 will not survive, right? You need an environment which supports the growth 301 00:19:45.500 --> 00:19:49.600 of these cells and that's why viable sites are important, right? And 302 00:19:49.900 --> 00:19:52.500 do you want to ask me what are the viable sites? Why 303 00:19:52.500 --> 00:19:55.700 is it that we can't inject directly in the pancreas? Would that 304 00:19:55.700 --> 00:19:59.900 would that be a next question? Yes. Where? Yeah. So that's an 305 00:19:59.900 --> 00:20:04.700 important question. So see where do we have these viable cells going? 306 00:20:04.700 --> 00:20:08.800 Where do we implant these viable cells? So please understand the problem 307 00:20:08.800 --> 00:20:11.700 is so the the simple question that you might ask why can't 308 00:20:11.700 --> 00:20:15.000 we just take these cells which is differentiated into beta cells and 309 00:20:15.000 --> 00:20:18.400 this inject them directly into the pancreas, you know where the beta 310 00:20:18.400 --> 00:20:22.800 cells are? It's a simple logical process, right? Does it work? Unfortunately 311 00:20:22.800 --> 00:20:27.800 no because first and foremost pancreas is a retroperitoneal organ. Please 312 00:20:27.800 --> 00:20:31.200 understand accessibility is a problem. You want to inject it into a 313 00:20:31.200 --> 00:20:36.600 retroperitoneal site. Accessibility is a problem. Second pancreas is a very 314 00:20:36.600 --> 00:20:40.900 very sensitive tissue. The moment any kind of a minor damage is 315 00:20:40.900 --> 00:20:45.200 sensed in the organ, it sends out its proteolytic enzymes. There is 316 00:20:45.200 --> 00:20:50.000 high inflammation inside the organ. Now forget the implanted cells. The pancreas 317 00:20:50.000 --> 00:20:54.600 itself will auto lysis itself through the enzymes. There's a terrible state 318 00:20:54.600 --> 00:20:59.100 you're going to end up the patient with. Thereby implanting these cells 319 00:20:59.100 --> 00:21:02.500 in the pancreas is not a viable option. You need to look 320 00:21:02.500 --> 00:21:07.400 for alternative sites. You know implanted implanting it into the splenic vein, 321 00:21:07.800 --> 00:21:11.700 hepatic vein etc. has been shown to be quite you know quite 322 00:21:11.700 --> 00:21:15.700 shown quite promising results in certain studies. But like I said earlier 323 00:21:15.700 --> 00:21:19.800 on, fundamentally a few months ago we have had you know you 324 00:21:19.800 --> 00:21:23.300 know a patient undergoing implant in the anterior abdominal wall in the 325 00:21:23.300 --> 00:21:28.300 rectus sheath, right? And there it was viable. The cells survived and 326 00:21:28.300 --> 00:21:33.400 post 75 days of the transplant, we were actually able to stop 327 00:21:33.500 --> 00:21:38.400 insulin therapy for the patient. Patients stopped insulin therapy, continued to have 328 00:21:38.400 --> 00:21:43.100 normal sugars. We're still doing well as per the records, right? So 329 00:21:43.100 --> 00:21:47.200 that's the process of how we are able to differentiate embryonic I 330 00:21:47.200 --> 00:21:52.200 mean differentiate stem cells to adult beta cells. Sir, moving on 331 00:21:52.200 --> 00:21:57.100 to the next question that is is there a role for immunosuppression 332 00:21:57.100 --> 00:22:01.200 in stem cell therapy for diabetes? If yes, then if you can 333 00:22:01.200 --> 00:22:06.500 elaborate about it. Yeah, see I would say still stem 334 00:22:06.500 --> 00:22:10.800 cell therapy continues to be a soft therapy. It is It's a 335 00:22:10.900 --> 00:22:13.800 therapy which is foolproof. This you know we have come to a 336 00:22:13.800 --> 00:22:18.600 point where completely successful patient is going to be insulin independent for 337 00:22:18.600 --> 00:22:20.900 the rest of the rest of his his or her life. No, 338 00:22:21.200 --> 00:22:25.600 it is still considered to be a soft therapy. Why? Because what 339 00:22:25.600 --> 00:22:29.000 is the again with focus to type one diabetes. Type one diabetes, 340 00:22:29.000 --> 00:22:34.400 the problem is autoimmunity, right? The GAD antibodies, zinc transporter antibodies, anti-insulin 341 00:22:34.400 --> 00:22:39.600 antibodies, they continue to create autoimmunity. They continue to damage the cells. 342 00:22:39.600 --> 00:22:45.200 That's the ongoing fundamental problem in type one diabetes. So unfortunately 343 00:22:45.200 --> 00:22:48.900 in the current scenario, right? We still need immunosuppression to a certain 344 00:22:48.900 --> 00:22:54.000 extent. Yeah, that's one thing. Fortunately, I would say fortunately compared 345 00:22:54.000 --> 00:22:58.300 to allergenic transplant. Let's say I'm taking the islet cells from another 346 00:22:58.300 --> 00:23:03.500 person and transplanting it to another person B. There 347 00:23:03.500 --> 00:23:07.100 there is that's what we call allergenic stem cell allergenic beta cell 348 00:23:07.100 --> 00:23:11.300 transplant or islet cell transplant. The problem there is there we require 349 00:23:11.300 --> 00:23:15.700 full-fledged immunosuppression because we are using allergenic cells. On the other hand, 350 00:23:15.700 --> 00:23:19.700 if you're using using the cells as autologous source, cells from your 351 00:23:19.800 --> 00:23:23.000 own body, what are the autologous stem cells we have talked about? 352 00:23:23.500 --> 00:23:28.100 iPSC cells, induced pluripotent stem cells. I take my own skin fibroblast, 353 00:23:28.700 --> 00:23:33.100 I change it into iPSC cells, I differentiate into adult pancreatic beta 354 00:23:33.100 --> 00:23:36.700 cells, I inject it back. It's my own cells from my own 355 00:23:36.700 --> 00:23:40.900 body, autologous cells. The advantage with autologous cells is it's because it's 356 00:23:40.900 --> 00:23:46.000 your own cells. The requirement for immunosuppression is relatively less, 357 00:23:46.600 --> 00:23:51.300 right? Yes, there is still a requirement for immunosuppression, but probably with 358 00:23:51.300 --> 00:23:54.200 lower number of drugs maybe tacrolimus etc. one or two drugs are 359 00:23:54.200 --> 00:23:58.200 used for a certain duration and patients continue to do. So yes, 360 00:23:58.200 --> 00:24:02.500 there is still a requirement of immunosuppression because of these fundamental reasons. 361 00:24:02.600 --> 00:24:08.100 The autoimmunity continues and especially if you're using allergenic mesenchymal stem cells, 362 00:24:08.600 --> 00:24:12.800 right? There you definitely need to full-fledged immunosuppression because these are not 363 00:24:12.800 --> 00:24:16.400 your own cells. Of course, the extent of immunosuppression may be less 364 00:24:16.400 --> 00:24:20.400 compared to transplanting adult beta cells or islet cells because these are 365 00:24:20.500 --> 00:24:23.400 even if we take MSC cells, they are they are stem cells, 366 00:24:23.400 --> 00:24:26.800 right? Although it may be from another source, another donor, they are 367 00:24:26.800 --> 00:24:32.000 still stem cells. So the allergenic or the immune response generated 368 00:24:32.200 --> 00:24:35.800 by these stem cells may be less compared to an adult you 369 00:24:35.800 --> 00:24:39.300 know transplant, adult tissue transplant, what is being done. So in that 370 00:24:39.300 --> 00:24:43.300 sense, yes, there is still a requirement for immunosuppression, but it is 371 00:24:43.400 --> 00:24:49.000 much lower compared to how you know adult cells are being transplanted. 372 00:24:49.000 --> 00:24:52.600 I mean just like any other transplant we talk about, liver transplant 373 00:24:52.900 --> 00:24:57.400 or kidney transplant, right? These are all adult transplantation procedures we're talking 374 00:24:57.400 --> 00:25:02.400 about. There you need full-blown full-fledged immunosuppression, but here the requirement is 375 00:25:02.400 --> 00:25:05.900 less, you know, because we are dealing with the natives. We are 376 00:25:05.900 --> 00:25:09.600 dealing with the early cells, the undifferentiated cells, what we call these 377 00:25:09.600 --> 00:25:13.800 stem cells, right? So that's the answer to the question. Sir, moving 378 00:25:13.800 --> 00:25:17.900 on to the second last question for today's session that is what 379 00:25:17.900 --> 00:25:21.200 are the main safety concerns that you would like to highlight with 380 00:25:21.200 --> 00:25:24.400 stem cell therapy in diabetes? Whatever you have come across, yeah. Yeah. 381 00:25:26.300 --> 00:25:30.700 Yes, yes. So I would say first before discussing the safety concerns, 382 00:25:30.700 --> 00:25:33.600 I would like to put across put across the positive aspects. What 383 00:25:33.600 --> 00:25:36.200 are the advantages? Let's look at that first. So we have talked 384 00:25:36.200 --> 00:25:38.700 a lot about the advantages, but I would would like to reiterate 385 00:25:38.700 --> 00:25:44.000 it again. Fundamentally, the concept of stem cell therapy is your 386 00:25:44.200 --> 00:25:47.300 taking your own cells. You're using your own kit, your own repairing 387 00:25:47.300 --> 00:25:50.400 kit within your body, your own stem cells and you're allowing that 388 00:25:50.400 --> 00:25:53.600 to heal your body. Isn't so isn't that a wonderful science that 389 00:25:53.600 --> 00:25:57.200 we're looking into? You're using your own cells and you're healing your 390 00:25:57.200 --> 00:26:00.300 own damage state, right? what you were born with. You're using your 391 00:26:00.300 --> 00:26:03.500 own cells and you're healing your own damage state. So fundamentally it's 392 00:26:03.500 --> 00:26:08.700 a safe, effective, well tolerated, very very promising 393 00:26:08.700 --> 00:26:11.900 results, right? So that's the first key point that you need to 394 00:26:11.900 --> 00:26:16.300 keep in mind. And when you compare it with the usual pharmacotherapy 395 00:26:16.300 --> 00:26:19.100 that we use, the drugs that we use, you know for multiple 396 00:26:19.100 --> 00:26:24.100 conditions, of course pharmaceutical agents we know they're not native 397 00:26:24.100 --> 00:26:27.100 to our body, right? These are drugs fundamentally. You're doing chemical bombing 398 00:26:27.100 --> 00:26:29.700 in the system. So they will come with the plethora of side 399 00:26:29.700 --> 00:26:33.600 effects, no matter what. But here you're using your own body cells. 400 00:26:34.400 --> 00:26:38.100 The greatest advantage is you know the literally the side effect you 401 00:26:38.100 --> 00:26:40.800 don't need to be much worried about. I would say the only 402 00:26:40.800 --> 00:26:44.200 concerns we need to have of course is when you're using very 403 00:26:44.200 --> 00:26:47.800 very pluripotent, I mean using cells with a much higher capacity of 404 00:26:48.200 --> 00:26:52.800 you know differentiation. For example, the pluripotent stem cells, there there is 405 00:26:52.800 --> 00:26:56.600 a in theory there's a potential risk of teratoma etc. For example, 406 00:26:56.600 --> 00:26:59.600 when you're using this challenge was a big this concern was a 407 00:26:59.600 --> 00:27:03.700 big concern as far as using embryonic stem cells. Is a teratoma 408 00:27:03.700 --> 00:27:07.000 going to be formed with these cells? That was one major concern. 409 00:27:07.300 --> 00:27:11.500 So the same concern still holds good with iPSC cells because iPSC 410 00:27:11.500 --> 00:27:15.800 cells also pluripotent stem cells. So the same concern continues to be 411 00:27:15.800 --> 00:27:18.200 there, but literally I don't think as far as I know I 412 00:27:18.200 --> 00:27:21.900 don't think there are any reports which have documented a teratoma forming. 413 00:27:22.600 --> 00:27:25.400 So that's one concern that we always have, but with the mesenchymal 414 00:27:25.400 --> 00:27:28.700 stem cells of MSC therapy, you know that concern literally I would 415 00:27:28.700 --> 00:27:33.000 say uh it's not that because they are not pluripotent, right? They 416 00:27:33.000 --> 00:27:38.000 are pluripotent. So their differentiation capacity is limited to the mesodermal lineage. 417 00:27:38.900 --> 00:27:42.200 So that's one thing. Second thing is when you're playing with the 418 00:27:42.200 --> 00:27:46.400 genetics and the epigenetics, when you're changing the program of the cell 419 00:27:46.500 --> 00:27:51.700 using certain factors, using your certain vectors, right? There is always a 420 00:27:51.900 --> 00:27:56.400 challenge, always a concern or possibility of hitting the wrong target. You 421 00:27:56.400 --> 00:28:00.700 might end up causing a mutation in the wrong place, right? So 422 00:28:00.700 --> 00:28:05.900 misinformation, mutation through that wrong genetic coding, through that 423 00:28:06.200 --> 00:28:10.300 wrong epigenetic expression, all those are a possibility. So you might not 424 00:28:10.300 --> 00:28:13.900 get the desired effect or there is also in theory a possibility 425 00:28:13.900 --> 00:28:18.200 of ending up with you know some other problem, some other you 426 00:28:18.200 --> 00:28:21.800 try you intended to give that treatment for some purpose, something else 427 00:28:21.800 --> 00:28:24.600 turns up. You know this is all in theory, but fundamentally let 428 00:28:24.600 --> 00:28:28.900 me tell you the stem cells are so smart. They actually work 429 00:28:29.000 --> 00:28:32.900 on the environmental cues, they and the environmental cues, what is around 430 00:28:32.900 --> 00:28:35.800 them, they respond to that. So if we have the right response 431 00:28:35.800 --> 00:28:40.200 around them, they will fundamentally differentiate into the right tissue. See the 432 00:28:40.200 --> 00:28:44.400 nature is much more intelligent than what we see. See if the 433 00:28:44.400 --> 00:28:48.000 nature has the capacity that when we are born in the process 434 00:28:48.000 --> 00:28:51.200 of growth in the fetus, when the nature is given so much 435 00:28:51.200 --> 00:28:56.100 intelligence that the cells can automatically find the cues from a ball 436 00:28:56.100 --> 00:28:59.100 of cells. They are able to differentiate into a full grown human 437 00:28:59.100 --> 00:29:03.400 to the right organ when the nature has given that intelligence. That 438 00:29:03.400 --> 00:29:06.900 means it's a very sophisticated system we are looking at. So that's 439 00:29:06.900 --> 00:29:10.500 why these stem cell therapies I would say they are amazing. They 440 00:29:10.500 --> 00:29:14.200 are literally although what I've talked about this is in theory on 441 00:29:14.200 --> 00:29:18.300 paper that there is a risk involved, but in practice, you know 442 00:29:18.400 --> 00:29:21.800 it is so much foolproof. Nature has given that intelligence to the 443 00:29:21.800 --> 00:29:25.300 system that you know the cells more or less will end up 444 00:29:25.300 --> 00:29:28.800 in the right target, giving the right results, right? That's the beauty 445 00:29:28.800 --> 00:29:32.000 of using these cells. So the so of course because we are 446 00:29:32.000 --> 00:29:34.800 talking about the concerns, I had to bring up those concerns at 447 00:29:34.800 --> 00:29:37.800 least that is what we see in paper, you know the risk 448 00:29:37.800 --> 00:29:42.400 of teratoma, the risk of mutations etc. And of course you know 449 00:29:42.400 --> 00:29:45.300 maybe at times we might not be able to get the desired 450 00:29:45.300 --> 00:29:48.600 outcome what we what we want. Of course there this is not 451 00:29:48.600 --> 00:29:52.400 that this is a panacea for everything, you know. Of course certain 452 00:29:52.400 --> 00:29:55.900 patients we might not give get the results that we want. That 453 00:29:55.900 --> 00:30:01.300 possibility is also there, right? So again that depends on various factors. 454 00:30:01.300 --> 00:30:05.200 What is the kind of MSC pool that you're taking? Is it 455 00:30:05.200 --> 00:30:08.200 healthy cells that you've extracted? See if you take for example, if 456 00:30:08.200 --> 00:30:11.500 you take a stem cell reserve from a person who's having multiple 457 00:30:11.500 --> 00:30:15.600 comorbidities and multiple health conditions, the stem cell itself is going to 458 00:30:15.600 --> 00:30:19.500 be poor in quality. Is it not so? A person is or 459 00:30:19.600 --> 00:30:22.500 or or as another example, if you're taking stem cell from a 460 00:30:22.500 --> 00:30:26.900 very old or aged from the aging population, there also we see 461 00:30:27.300 --> 00:30:30.300 that the quality and the quantity of stem cells might be an 462 00:30:30.300 --> 00:30:34.500 issue, right? So these factors come into play where the results might 463 00:30:34.500 --> 00:30:38.900 be suboptimal depending on the stem cell population that we are taking, 464 00:30:39.000 --> 00:30:41.400 you know, for the therapy. So I would say these are the 465 00:30:41.400 --> 00:30:46.200 possibilities, you know these are the probable concerns that we need to 466 00:30:46.200 --> 00:30:48.800 keep in mind, but otherwise I would say these are more or 467 00:30:48.800 --> 00:30:51.900 less in theory that that we need to keep this in mind. 468 00:30:51.900 --> 00:30:55.400 But fundamentally what I've seen, you know, as far as practically is 469 00:30:55.400 --> 00:30:59.000 concerned, these cells are able to do the right thing for most 470 00:30:59.000 --> 00:31:03.000 patients when given on the right dose with the right concentration of 471 00:31:03.000 --> 00:31:07.100 stem cell. That's also important. You cannot give a suboptimal concentration of 472 00:31:07.100 --> 00:31:10.000 stem cells and expect the results to come out. You know a 473 00:31:10.000 --> 00:31:14.400 few million cells you know per kilogram body weight is generally required 474 00:31:14.900 --> 00:31:18.400 to reach to see the optimal outcome. So that cell concentration is 475 00:31:18.400 --> 00:31:22.100 also important. That is being done in the right way. We can 476 00:31:22.100 --> 00:31:27.300 expect quite phenomenal results in most cases and a very safe, right? 477 00:31:27.300 --> 00:31:31.300 and yet very effective method. Sir, moving on to the last question 478 00:31:31.300 --> 00:31:35.400 for today's session that is what could stem cell therapy mean for 479 00:31:35.400 --> 00:31:40.200 insulin dependency in future? Your take. Yeah, I think I've answered this 480 00:31:40.200 --> 00:31:44.300 in bits and pieces in the previous few questions also. Yeah. So 481 00:31:44.600 --> 00:31:48.000 as I mentioned, we are in a phase where we haven't been 482 00:31:48.000 --> 00:31:51.300 it. So the target, the gold standard that we look into is 483 00:31:51.300 --> 00:31:55.600 for most studies is what is the five-year insulin independence percentage that 484 00:31:55.600 --> 00:31:59.100 we have been able to achieve and the cohort of patients maybe 485 00:31:59.100 --> 00:32:01.800 in the clinical trial. We would like to see out of 100 486 00:32:01.800 --> 00:32:04.800 patients, how many of them are able to achieve five-year insulin the 487 00:32:04.800 --> 00:32:08.600 independence, right? That's the gold standard that we are looking into. So 488 00:32:08.700 --> 00:32:10.700 I still the numbers are not that great, you know. We do 489 00:32:11.800 --> 00:32:16.100 most of these studies have shown promising results that insulin independence has 490 00:32:16.100 --> 00:32:19.700 been able to be may be able to achieve insulin independence probably 491 00:32:19.700 --> 00:32:23.600 in you know one and a half to two years currently. So 492 00:32:23.700 --> 00:32:28.900 we need to see what can be done to increase the viability 493 00:32:28.900 --> 00:32:32.600 of these cells and to provide extended periods periods of insulin independence 494 00:32:32.600 --> 00:32:36.200 for these patients. So what are the possibilities? There's a lot of 495 00:32:36.200 --> 00:32:39.700 interesting research which is being done and there is few phase one 496 00:32:39.700 --> 00:32:43.000 phase two clinical trials which are in fact showing very promising results. 497 00:32:43.100 --> 00:32:46.800 There are few companies, a few protocols where I know that they're 498 00:32:46.800 --> 00:32:52.200 having they're coming up with encapsulation technologies. They encapsulate the cells, right? 499 00:32:52.200 --> 00:32:54.800 Before injecting it or before doing the transplant so that we are 500 00:32:54.800 --> 00:33:00.100 able to give or protection from autoimmunity, right? Vortex 501 00:33:00.100 --> 00:33:04.500 and other such companies are there which which phenomenally they're doing a 502 00:33:04.500 --> 00:33:08.400 great work, right? where we are able to show that through certain 503 00:33:08.400 --> 00:33:13.700 encapsulation technologies we are able to protect the the transplanted 504 00:33:13.700 --> 00:33:18.300 cells from autoimmune damage. Thereby potentially we are able to extend the 505 00:33:18.300 --> 00:33:20.300 life of these cells and able to actually increase the period of 506 00:16:43.400 --> 00:16:43.400 insulin independence for these patients, right? So I would say much more 507 00:16:48.400 --> 00:16:49.900 work has to be done. No doubt about it. Probably it might 508 00:16:51.700 --> 00:16:54.100 take a decade or more to come to a phase where we 509 00:16:54.500 --> 00:16:54.500 get excellent numbers with respect to achieving insulin independence etc. But 510 00:17:01.100 --> 00:17:02.100 we are in the right direction. We are seeing very promising early 511 00:17:02.100 --> 00:17:03.000 results. Early 512 00:17:03.000 --> 00:17:04.600 clinical trials 513 00:33:43.600 --> 00:33:48.200 are showing very promising results. So it's just a matter of modifying 514 00:33:48.200 --> 00:33:52.000 the technique, finding out methods, how to protect the cells, how to 515 00:33:52.000 --> 00:33:55.600 ensure that we are able to have viable cells long-term. They continue 516 00:33:55.600 --> 00:33:59.300 to produce the insulin that is needed in the long-term. So that's 517 00:33:59.300 --> 00:34:03.000 the goal going ahead. I think the next decade or so we 518 00:34:03.000 --> 00:34:07.200 should definitely be able to see very very promising outcomes in this. 519 00:34:07.600 --> 00:34:11.100 And that's what I am expecting too. And you know I'm also 520 00:34:11.100 --> 00:34:14.300 looking forward to work on you know projects and generally that's the 521 00:34:14.300 --> 00:34:17.600 area of my interest, type one diabetes trying to see how we 522 00:34:17.600 --> 00:34:21.300 can you know help these patients by seeing how we can achieve 523 00:34:21.300 --> 00:34:25.200 longer periods of insulin independence, right? That's a very very interesting and 524 00:34:25.200 --> 00:34:28.500 much needed area that we need to work upon. Yeah, that's what 525 00:34:28.500 --> 00:34:30.200 I am looking forward to. Yes.