1 00:00:00,000 --> 00:00:02,667 (heart beating) 2 00:00:07,030 --> 00:00:10,060 The human body is an amazing biological machine 3 00:00:11,520 --> 00:00:13,910 composed of a myriad of complex components 4 00:00:13,910 --> 00:00:16,683 medical science is just now beginning to understand. 5 00:00:18,030 --> 00:00:21,400 New technologies provide incredible images and new insights 6 00:00:21,400 --> 00:00:23,680 into how everything works, 7 00:00:23,680 --> 00:00:27,100 and in many ways, at the heart of it all is, 8 00:00:27,100 --> 00:00:28,453 well, the heart. 9 00:00:30,004 --> 00:00:32,671 (pulsing music) 10 00:00:33,630 --> 00:00:35,640 But heart disease is the number one 11 00:00:35,640 --> 00:00:37,183 cause of death worldwide. 12 00:00:38,220 --> 00:00:40,670 killing more than eight million people each year. 13 00:00:42,760 --> 00:00:46,960 Cardiac infarction, more commonly known as a heart attack, 14 00:00:46,960 --> 00:00:48,730 can happen without warning, 15 00:00:48,730 --> 00:00:51,810 killing heart muscle cells immediately. 16 00:00:51,810 --> 00:00:54,050 Even if the patient recovers, 17 00:00:54,050 --> 00:00:56,063 the damage to their heart may not. 18 00:00:58,470 --> 00:01:01,130 And so we want to somehow improve the function 19 00:01:01,130 --> 00:01:02,753 of that heart tissue. 20 00:01:05,090 --> 00:01:06,670 So all around the world, 21 00:01:06,670 --> 00:01:08,300 researchers are determined to learn 22 00:01:08,300 --> 00:01:09,863 how to fix a broken heart. 23 00:01:11,670 --> 00:01:14,090 Exploring multiple paths of inquiry, 24 00:01:14,090 --> 00:01:16,673 to innovate new bio-engineering methods, 25 00:01:18,010 --> 00:01:21,663 even developing the technology to print a new heart. 26 00:01:26,390 --> 00:01:28,290 Dr. Warren Grayson is a professor 27 00:01:28,290 --> 00:01:31,950 of biomedical engineering at Johns Hopkins University. 28 00:01:31,950 --> 00:01:35,430 His own work focuses on utilizing 3D printing techniques 29 00:01:35,430 --> 00:01:37,643 to aid facial bone regeneration. 30 00:01:38,530 --> 00:01:40,850 He also studies pioneering new research 31 00:01:40,850 --> 00:01:43,333 in regenerative medicine from around the world. 32 00:01:44,830 --> 00:01:47,650 Could we build something that's biological replacement 33 00:01:47,650 --> 00:01:51,440 that can either augment the normal function of the heart 34 00:01:51,440 --> 00:01:53,320 and in the most extreme conditions, 35 00:01:53,320 --> 00:01:56,810 I think the dream is could we actually build a new heart? 36 00:01:56,810 --> 00:02:00,673 An imbiological heart to replace that organ. 37 00:02:02,050 --> 00:02:03,320 This is a reconstruction 38 00:02:03,320 --> 00:02:05,050 of our circulatory system. 39 00:02:05,050 --> 00:02:06,813 Based on actual medical data. 40 00:02:10,620 --> 00:02:12,480 Blood vessels extend a total length 41 00:02:12,480 --> 00:02:14,313 of about 100,000 kilometers, 42 00:02:15,410 --> 00:02:17,843 or, about two and a half times around the globe. 43 00:02:21,400 --> 00:02:24,910 They deliver oxygen and nutrients to every corner, 44 00:02:24,910 --> 00:02:26,713 and take waste products away. 45 00:02:30,400 --> 00:02:34,540 They also serve as an organ-to-organ communication system. 46 00:02:34,540 --> 00:02:36,180 Transporting messaging molecules 47 00:02:36,180 --> 00:02:37,880 vital to our health and wellbeing. 48 00:02:39,200 --> 00:02:43,323 Including instructions, directing repair and regeneration. 49 00:02:46,510 --> 00:02:49,820 The heart is the engine of this circulatory network, 50 00:02:49,820 --> 00:02:51,763 pumping blood throughout our bodies, 51 00:02:52,990 --> 00:02:55,993 so any disruption can have dire consequences. 52 00:02:59,030 --> 00:03:01,140 But the heart is difficult to treat, 53 00:03:01,140 --> 00:03:04,093 due to a rather unique and troublesome characteristic. 54 00:03:06,530 --> 00:03:08,190 Many organs continue working 55 00:03:08,190 --> 00:03:10,643 as old cells are replaced by new ones. 56 00:03:12,680 --> 00:03:16,673 However, that process occurs very slowly in the heart. 57 00:03:17,930 --> 00:03:20,690 It's believed that only 30% of its cells 58 00:03:20,690 --> 00:03:23,213 are replaced over 50 years. 59 00:03:25,960 --> 00:03:28,010 So once the heart is damaged, 60 00:03:28,010 --> 00:03:31,043 it takes a long time for recovery to take place. 61 00:03:32,440 --> 00:03:34,843 How can new heart cells be generated? 62 00:03:35,860 --> 00:03:40,430 It appears, tiny extracellular bubbles, called exosomes, 63 00:03:40,430 --> 00:03:44,370 some hidden within the heart, play a key role. 64 00:03:44,370 --> 00:03:47,113 They contain a message that can rebuild the heart. 65 00:03:48,840 --> 00:03:50,603 Let's make more and more cells. 66 00:03:51,800 --> 00:03:55,200 So if a damaged heart receives an infusion 67 00:03:55,200 --> 00:03:58,330 of artificially created messaging molecules, 68 00:03:58,330 --> 00:04:00,413 this could speed up the process. 69 00:04:01,590 --> 00:04:03,757 (beating) 70 00:04:06,440 --> 00:04:09,430 Renown researcher, Dr. Eduardo Marban, 71 00:04:09,430 --> 00:04:12,270 tested this theory by giving with mice, 72 00:04:12,270 --> 00:04:14,603 that had experienced cardiac infarction. 73 00:04:16,080 --> 00:04:18,053 The results were dramatic. 74 00:04:19,410 --> 00:04:22,693 This is the wall of the heart after cardiac infarction. 75 00:04:23,700 --> 00:04:26,710 The cells on the right side have died. 76 00:04:26,710 --> 00:04:28,443 And the wall has become thin. 77 00:04:31,010 --> 00:04:33,610 But, in mice that received these additional 78 00:04:33,610 --> 00:04:38,030 messaging molecules, the number of cells had increased, 79 00:04:38,030 --> 00:04:39,863 and the wall had become thicker. 80 00:04:42,490 --> 00:04:45,010 Exosomes and their biology 81 00:04:45,010 --> 00:04:48,920 have sparked a revolution in our understanding, 82 00:04:48,920 --> 00:04:52,120 of how things work inside our bodies. 83 00:04:52,120 --> 00:04:55,220 If it can take the right ones 84 00:04:55,220 --> 00:04:58,460 from a defined therapeutic source 85 00:04:58,460 --> 00:05:01,010 they might be very powerful agents 86 00:05:01,010 --> 00:05:02,300 in the treatment of disease, 87 00:05:02,300 --> 00:05:05,473 in a way that defies all their connections. 88 00:05:07,460 --> 00:05:08,860 While Marban and his team 89 00:05:08,860 --> 00:05:12,300 continue their work to address cardiac disease, 90 00:05:12,300 --> 00:05:16,280 elsewhere, researchers investigate other approaches. 91 00:05:16,280 --> 00:05:20,363 Including the development of lab culture tissues and organs. 92 00:05:24,750 --> 00:05:28,120 This is Kenneth Chien, a world leading expert 93 00:05:28,120 --> 00:05:30,083 in the field of regenerative medicine. 94 00:05:31,480 --> 00:05:35,050 At Chien's lab, he uses embryonic stem cells 95 00:05:35,050 --> 00:05:38,703 to observe the formation of one organ almost everyday. 96 00:05:40,010 --> 00:05:43,230 Here, the researcher adds a certain signaling molecule 97 00:05:43,230 --> 00:05:44,603 to an ES cell, 98 00:05:45,850 --> 00:05:48,063 it's called WNT. 99 00:05:49,079 --> 00:05:52,250 WNT molecules are present in large quantities 100 00:05:52,250 --> 00:05:53,513 in dividing eggs. 101 00:05:57,210 --> 00:06:02,093 After one week, part of the cell is starting to pulse. 102 00:06:10,390 --> 00:06:15,183 Two days later, large ripples move across the flatten cell. 103 00:06:23,720 --> 00:06:26,383 This is the very beginning of a human heart. 104 00:06:29,360 --> 00:06:31,460 You can take an embryonic stem cell, 105 00:06:31,460 --> 00:06:33,610 that can become any cell. 106 00:06:33,610 --> 00:06:37,140 And then instruct it to specifically, almost entirely, 107 00:06:37,140 --> 00:06:41,083 become human beating ventricular muscle. 108 00:06:42,900 --> 00:06:44,923 This is an exciting event. 109 00:06:46,750 --> 00:06:48,270 Building on this excitement 110 00:06:48,270 --> 00:06:50,810 and enabling growth in biomedical research, 111 00:06:50,810 --> 00:06:53,280 is the development of a new type of material 112 00:06:53,280 --> 00:06:54,343 with which to work. 113 00:06:56,470 --> 00:06:59,830 Essentially reprogramming common human cells, 114 00:06:59,830 --> 00:07:01,580 such as skin cells. 115 00:07:01,580 --> 00:07:03,160 Scientists can now create 116 00:07:03,160 --> 00:07:08,160 induced pluripotent stem cells, or IPS for short. 117 00:07:10,910 --> 00:07:13,110 With the same transformative properties 118 00:07:13,110 --> 00:07:14,870 of embryonic stem cells, 119 00:07:14,870 --> 00:07:17,870 researchers in Israel are using IPS cells 120 00:07:17,870 --> 00:07:20,800 to develop startling new innovations. 121 00:07:20,800 --> 00:07:23,403 Even printing a miniature heart. 122 00:07:25,290 --> 00:07:27,100 This is the first time that the whole 123 00:07:27,100 --> 00:07:31,610 cellular heart, with blood vessel is printed. 124 00:07:31,610 --> 00:07:33,740 How did they do it? 125 00:07:33,740 --> 00:07:36,270 Tal Dvir and a team of research scientists 126 00:07:36,270 --> 00:07:40,080 at Tel Aviv University, harvested patients fatty tissue, 127 00:07:40,080 --> 00:07:43,463 to produce a personalized biological hydrogel. 128 00:07:43,463 --> 00:07:45,350 As well as IPS cells, 129 00:07:45,350 --> 00:07:48,733 manipulated to become cardiac invascular cells. 130 00:07:50,610 --> 00:07:53,760 Together, these form what Dvir calls bioinks. 131 00:07:55,680 --> 00:07:57,383 We have bioinks for the heart, 132 00:07:57,383 --> 00:07:59,880 and bioinks for the blood vessels, 133 00:07:59,880 --> 00:08:03,200 and then we use a 3D printer to print whole hearts 134 00:08:03,200 --> 00:08:05,213 with the major blood vessels. 135 00:08:06,770 --> 00:08:11,063 The next stage is to mature these hearts, in the lab, 136 00:08:12,233 --> 00:08:15,630 to help the cells, or teach them how to interact 137 00:08:15,630 --> 00:08:18,550 with each other and how to provide electrical signal 138 00:08:18,550 --> 00:08:23,214 into every contraption or pumping ability of the heart. 139 00:08:23,214 --> 00:08:27,950 In a year or two we hope to take these hearts 140 00:08:27,950 --> 00:08:31,130 and transplant them in smaller animal, models and rats 141 00:08:31,130 --> 00:08:32,970 or whatever, rabbits. 142 00:08:32,970 --> 00:08:36,010 Astounding, no doubt, and while much more work 143 00:08:36,010 --> 00:08:38,130 must be done to scale up the study, 144 00:08:38,130 --> 00:08:40,720 from printing rabbit sized organs to a truly 145 00:08:40,720 --> 00:08:45,320 human sized heart, its impact, may be more immediate. 146 00:08:45,320 --> 00:08:48,830 By being able to create something like that, inside a lab, 147 00:08:48,830 --> 00:08:51,620 you can start testing (music drowns out speaker) 148 00:08:51,620 --> 00:08:53,540 It's definitely a positive, it definitely moves 149 00:08:53,540 --> 00:08:57,630 the field forward in terms of understanding basic biology, 150 00:08:57,630 --> 00:09:00,593 basic cell biology, and understanding conduct biology. 151 00:09:01,810 --> 00:09:04,360 And, yet, another element of Nor's study 152 00:09:04,360 --> 00:09:07,313 could result in medical applications more quickly. 153 00:09:08,760 --> 00:09:11,270 Using these same bioprinting techniques, 154 00:09:11,270 --> 00:09:15,230 the researchers developed a vascularized cardiac patch, 155 00:09:15,230 --> 00:09:18,110 leading to potentially new ways to repair the damaged 156 00:09:18,110 --> 00:09:19,493 done by heart attacks. 157 00:09:20,850 --> 00:09:22,870 And so the idea there is that 158 00:09:22,870 --> 00:09:25,820 you can't remove that scar tissue entirely, 159 00:09:25,820 --> 00:09:27,810 but if you can plant a patch over it 160 00:09:27,810 --> 00:09:29,130 so you think of it as, you know, 161 00:09:29,130 --> 00:09:32,443 a cardiac band-aid in the sense, and you place over it, 162 00:09:33,400 --> 00:09:35,950 then that has contractability 163 00:09:35,950 --> 00:09:38,940 then it kind of augments that thinning wall. 164 00:09:38,940 --> 00:09:41,130 It makes it thicker and it also provides 165 00:09:41,130 --> 00:09:42,880 certain strength through that wall. 166 00:09:43,930 --> 00:09:45,910 So the cells campaign with that matrix 167 00:09:45,910 --> 00:09:47,380 is all entirely biological 168 00:09:47,380 --> 00:09:49,930 and it's all entirely back compatible, 169 00:09:49,930 --> 00:09:52,930 it can integrate with anybody, there's not gonna be any 170 00:09:52,930 --> 00:09:55,400 immune injection as a response to that, 171 00:09:55,400 --> 00:09:58,063 because the cells come from that particular patient. 172 00:09:59,290 --> 00:10:02,440 I believe that in 10 years that there will be printers 173 00:10:02,440 --> 00:10:07,080 in every hospital that will print tissues and organs 174 00:10:07,080 --> 00:10:09,843 that will then be transplanted in new patients. 175 00:10:11,900 --> 00:10:13,080 Doctor Grayson believes 176 00:10:13,080 --> 00:10:14,913 that's an optimistic timeline. 177 00:10:15,910 --> 00:10:19,100 But given the remarkable advances of biomedical engineering, 178 00:10:19,100 --> 00:10:22,853 doctors may soon truly learn how to fix a broken heart. 179 00:10:23,800 --> 00:10:25,640 Within science there's always promise 180 00:10:25,640 --> 00:10:26,970 and there's always hope. 181 00:10:26,970 --> 00:10:29,420 And so each of these breakthroughs takes us, you know, 182 00:10:29,420 --> 00:10:32,850 that step further and maintains that hope in getting there.