引用本文： 康裕建. 再生醫學-醫療模式轉化的催化劑—2017 年 TEDx 合江亭演講. 華西醫學, 2018, 33(12): 1466-1470. doi: 10.7507/1002-0179.201812066 復制
How many of you are 60 years old and over? Please raise your hands. How many of your parents are over 60 years old? Please raise your hands. Do you know or have you heard what people over 60 years old often talk about? What I often heard is this: “My doctor placed a couple of stents in my hearts” or “My doctor told me I need seven stents in my heart, I just placed a couple and wait for a while to place more”. Then they will talk about saving money for future disease treatment. I call this aging population syndrome, which is saving money for disease. How many people involved in this aging population? According to WHO, between 2000 and 2050, the number of people aged 60 years old and over is expected to increase from 605 million to 2 billion, about 11% to 22% of the world population.
Our life span is elongated, this is a good news. But there are about 80% of the ageing population suffer from serious illness. Think about this, if I were laid on bed from age 80 to 90 under daily medical attention, causing serious social and family burdens, what is the point to elongate my life span? Then someone asks me you can now make 3D bio-printed blood vessels, how about print organs for replacement? Yes, the 3D bio-printing technology would allow us to develop such applications. But I would like to tell you that I myself and my team would not make effort to print human organs for transplantation. Organ replacement is a disease-based end stage treatment, which does save life, but does not meet today’s need for improving quality of life. I believe we should transform the disease-based medication to personalized healthcare, focusing on improving the quality of life. I tell you why?
One of my friends recently told me that his doctor told him his coronary arteries already have 30% blocked because of atherosclerosis plaques, but cannot do much except wait for further growth of the plaques to cause life threatening problem, then bypass or vascular stents can be used to reopen the vessel conduit. What he can do now? The only option is to use some Statins drugs to slow, but not to stop, the growth of the plaques. In another word, he waits for his disease to grow to meet the standardized treatment procedure, i.e., standard disease-based medication. By then he would suffer from a long-term reduced blood supply to many organs, and already had many personalized chronic diseases.
My friend asked me: Can doctor just simply stop the growth or remove the plaques from me, so that I will never develop to the end stage disease? I told him not now, but we definitely can do it in the future if we take action now. Our modern age knowledge and big data information generated from clinical practice allow us to create new technology, called Regenerative Medicine.
So what is regenerative medicine? Why do we need it? And how does it work? Regenerative medicine simply is to recover the function of failing organs through integrated approaches involving stem cells and related technologies. Stem cells are naturally occurred in our body and capable of repairing injured tissues. For instance, if you have a finger cut, you may not do anything but it is healed without notice. This is the process of self-repair. In this process, the injured tissue releases injury signals to recruit the repair material to the injury site. The materials to repair the injury are stem cells. Thus, stem cells are naturally existing personalized medication.
Why do we develop chronic disease although we are equipped with personalized medication or stem cells? We can think about this in two ways; the first is that if an organ is constantly insulted and the damage is overwhelming the capacity of stem cells for functional repair, a non-functional repair will take place, such as the formation of scar tissue, which will interfere with normal function leading to chronic disease. The second, in aging population, the self-repair capacity is reduced leading to cumulative organ damage from the same insult that may not cause disease in youth. These two problems are all related to the shortage of stem cells.
Now you may wonder how to make more stem cells available for regenerative medicine? Let’s first examine where stem cells are in our body. We all start from a single fertilized egg cell in our mom’s womb. During the embryonic period, the embryo develops into three layers, the ectoderm, the endoderm, and the mesoderm; and stem cells rapidly divide and differentiate to different organs. Some stem cells are also stored in our organs, such as mesenchymal stem cells in the mesoderm organs and bone marrow stem cells in our bone marrow. These stem cells are mobilized locally and from bone marrow when an organ is injured and needs to be repaired. The stem cell can be removed from our body, expanded outside of our body, and then reintroduced to our body to repair the injured organ.
Now you may ask how do stem cells work in our body? First, stem cells once in our body need to know where to go. On the surface of the stem cells there are detectors that can detect the injury signal, then where the injury signal comes from? Second, once the stem cells arrive in the injured organ, how do they act to repair the injury?
The first, how does an injured organ send signals? When an organ is injured, it will release some cellular molecules or chemicals, attracting stem cells to the injured site for repairing. But if there are not enough stem cells, a scar tissue will be formed to make a non-functional repair. The tissue will no longer send injury signals. If you introduce stem cells into the body, they don’t know where to go. If you simply force stem cells into the injured organ such as through injection, they would not stay in place. Let’s think about the ceramic tiles covered on the floor in your house, what would happen if one of the tiles was damaged, but cannot be replaced because you do not have the replacement tile? You may use cement to cover the empty space, which doesn’t look or feel the same. Now, you get the replacement tile, what you would do is to remove the cement first, and then place the tile in place.
The non-functionally repaired organ was covered by scar tissue, to repair it we need to remove the scar tissue first. This scar tissue removing re-activates the tissue injury signaling, or changes the injury from chronic to acute state, calling for self-repair mechanism to work again. By providing sufficient stem cells through cell expansion from the same patient, the re-repair takes place, leading to organ regeneration.
The second, how do stem cells repair the injured organ? We did an experiment. We removed mesenchymal stem cells from monkey’s own fat tissue. After cell expansion, we packed the cells in a spheroid envelop composed of biodegradable materials; we call it Biosynsphere. We used the biosynspheres as bio-ink and applied the bio-ink to a novel 3D bio-printer to produce a stem cell vascular graft that was covered by a prosthetic vascular graft. The hybrid vascular graft was implanted as an interposition graft to replace a 2-cm-long segment of the abdominal aorta in the monkeys. We observed the changes of the implanted grafts at different times, and found that a complete vessel structure was formed about 4 weeks after the implantation, including endothelium layer, smooth muscle layer, and integrated collagen structure. In this process, anticoagulant heparin was used only in the first 5 days to prevent blood clotting. We made 47 implantations in 34 monkeys, and all of the regenerated vessels have normal function for the longest observation of more than 280 days.
I need to tell you that the mesenchymal stem cells are removed from the monkey’s own body, only 5 gram fat tissue is sufficient for a 2 cm vascular graft. It has no problem at all to remove 5 gram fat from anyone of us, even you are a skim model girl. If you say “I am too old”; no problem, you can ask your son or grandson to donate 5 gram fat for your use. It has been proven it does work well in monkeys.
So what can we conclude? First, injured organ is capable of a self-regeneration as long as there are sufficient repair materials supplied; second, the fat tissue mesenchymal stem cells are good enough and efficient for regeneration of multiple tissues of the blood vessel; and, third, personalized medicine is realized by rejuvenation of the naturally occurred self-repair process. This process isorchestrated by the injured site. We call this “Destination-Engaged Vector Evolving Lineage Organ Regeneration”, or simply called DEVELOR.
Thus, we can use our own stem cells to repair cumulative damages at early stage, preventing the development of the end stage of chronic disease. This will transform our medical practice from disease-based medication to personalized healthcare focusing on improving the quality of life, not simply expanding life span. By 2050, most of you will reach to age 60, I hope when you gather together then, you will talk about something more exciting than saving money for disease.
Thanks all.
馮莉 譯四川大學華西醫院再生醫學研究中心（成都 610041）Email: fenglily31@hotmail.com
假如我們偶遇年逾古稀長輩們的閑聊，我們大概會聽到這些內容：“最近我的心臟剛裝了支架”“醫生告訴我需要裝 7 個支架，我現在只裝了 2 個”等等。然后，討論的話題必然會過渡到如何存錢治病。“存錢治病”本身似乎也已經成為現代老年群體必須面對的一種疾病，我給這種病起了個名字，叫做“人口老齡化綜合征”。那么，到底有多少人已經或者即將步入老齡呢？據世界衛生組織數據顯示，從 2000 年到 2050 年，全球 60 歲以上人口將從 6 億 500 萬飆升至 20 億，更可怕的是，其在全球總人口中的比例將從 11% 上升到 22%。
人均期望壽命的不斷延長絕對是件好事。可我們也應當看到，近 80% 的老齡人口不得不承受各種嚴重疾病帶來的痛苦和困擾。試想，如果我們整天躺在病床上，依靠各種藥物度過從 80 歲到 90 歲的每個日夜，還必須時刻擔心高額的醫療費用。這樣的“高壽”，又有什么意義呢？
接下來你一定會問我這樣的問題：既然 3D 生物打印血管已經成為現實，那么是否可以使用該技術打印人體器官，通過移植取代受損臟器，從而延長我們的生命呢？當然，3D 生物打印技術絕對可以讓這種夢想成為現實。但我要告訴大家，我和我的團隊不會將人體器官打印作為我們的目標。因為，器官移植只是針對疾病終末期的一種傳統治療方式，這種方式確實能夠挽救生命，但它仍然不能滿足當代人們對提高生命質量的需求。我堅信，聚焦于人類生命質量的提高，將傳統的“以病為本”的醫療模式向“以人為本”的個性化健康干預模式轉變，才是醫學發展的正確方向。
最近我的一個朋友被診斷為動脈粥樣硬化，他的冠狀動脈已經堵塞 30%。但醫生對此束手無策。我的朋友只能被動地服用一些降膽固醇的藥物來減緩而不是阻止斑塊的長大。動脈硬化是不可逆的，他只能坐等斑塊長大，甚至等到可能危及其生命時，才能通過搭橋手術或放置血管支架以重新打通血管。換句話說，在血管堵塞程度達到現有手術治療的標準之前，我朋友什么都干不了。這，就是標準的“以病為本”的傳統醫療模式。可是，當疾病達到治療“標準”的時候，我朋友身體內的許多器官已經因為長期血供不足而受到損害，他已經由于這種非常“個性化”的因素，患上了諸多慢性疾病。
朋友很無奈地問我，醫生為何不能立即阻止斑塊生長或者直接去除斑塊呢？那樣的話，他的病根本就不會發展到終末期。我告訴他，雖然當前的醫療水平還無法達到他的要求，但只要付諸行動，在未來我們一定能夠做到。現代醫學知識的積累和來源于臨床實踐的大數據信息，為創造“以人為本”的新技術提供了支撐，這種新醫療技術，就是我們所說的“再生醫學”。
再生醫學是什么？我們為什么需要再生醫學？它如何為攻克疾病服務？簡言之，再生醫學就是利用干細胞及其相關技術，使受損組織器官恢復功能的一種綜合方法。干細胞廣泛存在于我們體內，其具有修復受傷組織的能力。舉例而言，假如你的手不幸被劃破，即使你不接受任何治療，傷口也會自動愈合，這就是自我修復。在修復過程中，受傷組織會先釋放出損傷信號，促使體內的修復材料運送到損傷部位。這種修復材料就是干細胞。也就是說，干細胞就是一種自然存在的“個性化”治療藥物。
既然我們已經具備自我修復材料—干細胞，為何還會患上慢性疾病呢？這主要基于兩個方面的原因：一、當組織器官長期持續受損，其損傷超過干細胞的自我修復能力時，機體就會進入一種叫非功能性修復的狀態，例如瘢痕組織形成，它會阻礙組織器官發揮正常功能，導致慢性疾病發生；二、相同的損傷，在年輕的時候能夠自我修復，而到了老年，由于自我修復能力降低、修復不完全，因此損傷不斷累積，最終產生慢性疾病。這兩種原因其實歸根結底就是干細胞不足。
接下來你肯定會問，那要怎樣才能獲取足夠多的干細胞以用于再生醫學？首先我們需要確定干細胞在體內所處的位置。我們的人生旅程都開始于母親子宮里的一個受精卵細胞。在胚胎階段，胚胎發育為 3 個胚層：外胚層、內胚層和中胚層。期間，干細胞快速分裂并分化形成不同的器官。其中一部分干細胞會在出生后一直儲存在我們的器官里，如中胚層器官中的間充質干細胞、骨髓中包含的骨髓干細胞。與之相應，當器官受損需要修復時，干細胞有兩種來源：一是器官自身含有的干細胞，它們立刻可以原位修復；二是骨髓來源干細胞，從骨髓遷移至受損器官進行修復。這是人體內的自然修復方式，而醫學上運用干細胞進行人為治療的常用方式是將干細胞從體內取出，在體外培養擴增甚至修飾，然后被重新輸入體內去修復受損器官。
干細胞在體內如何工作呢？干細胞一旦返回體內，首先需要明確去哪兒？干細胞的表面具有各種偵測“損傷信號”的“探測器”，可“損傷信號”是從哪里來的呢？另外，一旦干細胞抵達受損器官，他們又是怎樣修復損傷的呢？
第一個問題，受損器官怎樣釋放損傷信號？當某個器官受損時，它會釋放一些細胞因子或化學物質，從而吸引干細胞去進行修復。但如果干細胞數量不足，非功能性修復就會發生，并形成瘢痕組織。一旦瘢痕組織形成，受損器官則不會再釋放信號。如果這時將體外培養的干細胞送回體內，由于沒有信號，它們并不知道受損器官在哪里，也就無法起到修復的作用。即使采用簡單粗暴的方式，比如將干細胞直接注射到受損器官，他們也不會乖乖地留在損傷處。大家可以想象一下家中的地磚，如果某塊地磚不小心碎掉，而此刻家里又沒有可替換的瓷磚，大家會怎么干？你有可能先用水泥來填補，但這就跟原來的地磚不一樣了。你不甘心，于是去市場買到同款瓷磚，但你需要先把那堆水泥去掉，才能把瓷磚貼上去。
同樣的道理，非功能性修復后的器官被瘢痕組織包覆，必須先將瘢痕組織去除，才能重新修復損傷。瘢痕組織去除后會重新釋放損傷信號，或者說將慢性損傷變為急性損傷，從而重新啟動自我修復機制。這時通過體外擴增足夠量的患者自體干細胞引入患者體內修復受損器官，器官再生將得以實現。
第二個問題，干細胞如何修復受損器官？在一項實驗中，我們從恒河猴自體脂肪組織中提取了間充質干細胞。在細胞擴增之后，將這些干細胞封裝在一層生物可降解材料制作的球狀包裹中，我們稱之為“生物磚”。這些“生物磚”作為墨汁被 3D 打印機打印成類似血管的管腔狀結構，其外層用人工血管包覆。然后，我們通過外科手術將 2 cm 打印的人工血管替換恒河猴的一段腹主動脈。通過不同時間點觀察植入血管的變化，我們發現在手術 4 周后，人工血管內就產生了完整的血管結構，包括內皮層、平滑肌層及膠原支持結構。在整個過程中，只需在前 5 天對恒河猴使用抗凝劑-肝素以防止凝血。截至目前，在 34 只恒河猴，47 次手術，最長達 280 多天的觀察過程中，所有移植的人工血管都在其體內發揮著正常功能。
我想告訴大家，實驗所用的間充質干細胞均從恒河猴自身提取。僅 5 g 脂肪組織就足夠制作出 2 cm 人工血管。提取 5 g 脂肪對任何一個人來說都不是問題，哪怕你是一名骨感超模。如果你認為自己年紀太大，不適合提取干細胞。請放心，可以請你的兒女或者孫輩捐獻 5 g 脂肪。猴子實驗已經證明這同樣具備可操作性。
綜上所述，第一，只要提供充足的再生材料，受損組織就能夠進行自我再生。其次，脂肪間充質干細胞完全可以滿足血管中多種組織的再生需要。第三，個性化醫療通過再次激活個體自主修復系統實現，這個過程由受損部位調控。我把這套理論體系稱為“Destination-Engaged Vector Evolving Lineage Organ Regeneration”，簡稱為 DEVELOR。
因此，我們能夠利用自身干細胞在疾病早期對累積損傷進行修復，防止病癥發展為慢性疾病終末期。這將有助于“以病為本”的傳統醫療模式向聚焦于提高生命質量，而不僅是延長壽命的“以人為本”的健康模式轉變。到 2050 年，當在座的大多數都已年逾古稀時，我希望大家再次相聚時，會聊一些比存錢治病更有趣的事情。
謝謝大家。
How many of you are 60 years old and over? Please raise your hands. How many of your parents are over 60 years old? Please raise your hands. Do you know or have you heard what people over 60 years old often talk about? What I often heard is this: “My doctor placed a couple of stents in my hearts” or “My doctor told me I need seven stents in my heart, I just placed a couple and wait for a while to place more”. Then they will talk about saving money for future disease treatment. I call this aging population syndrome, which is saving money for disease. How many people involved in this aging population? According to WHO, between 2000 and 2050, the number of people aged 60 years old and over is expected to increase from 605 million to 2 billion, about 11% to 22% of the world population.
Our life span is elongated, this is a good news. But there are about 80% of the ageing population suffer from serious illness. Think about this, if I were laid on bed from age 80 to 90 under daily medical attention, causing serious social and family burdens, what is the point to elongate my life span? Then someone asks me you can now make 3D bio-printed blood vessels, how about print organs for replacement? Yes, the 3D bio-printing technology would allow us to develop such applications. But I would like to tell you that I myself and my team would not make effort to print human organs for transplantation. Organ replacement is a disease-based end stage treatment, which does save life, but does not meet today’s need for improving quality of life. I believe we should transform the disease-based medication to personalized healthcare, focusing on improving the quality of life. I tell you why?
One of my friends recently told me that his doctor told him his coronary arteries already have 30% blocked because of atherosclerosis plaques, but cannot do much except wait for further growth of the plaques to cause life threatening problem, then bypass or vascular stents can be used to reopen the vessel conduit. What he can do now? The only option is to use some Statins drugs to slow, but not to stop, the growth of the plaques. In another word, he waits for his disease to grow to meet the standardized treatment procedure, i.e., standard disease-based medication. By then he would suffer from a long-term reduced blood supply to many organs, and already had many personalized chronic diseases.
My friend asked me: Can doctor just simply stop the growth or remove the plaques from me, so that I will never develop to the end stage disease? I told him not now, but we definitely can do it in the future if we take action now. Our modern age knowledge and big data information generated from clinical practice allow us to create new technology, called Regenerative Medicine.
So what is regenerative medicine? Why do we need it? And how does it work? Regenerative medicine simply is to recover the function of failing organs through integrated approaches involving stem cells and related technologies. Stem cells are naturally occurred in our body and capable of repairing injured tissues. For instance, if you have a finger cut, you may not do anything but it is healed without notice. This is the process of self-repair. In this process, the injured tissue releases injury signals to recruit the repair material to the injury site. The materials to repair the injury are stem cells. Thus, stem cells are naturally existing personalized medication.
Why do we develop chronic disease although we are equipped with personalized medication or stem cells? We can think about this in two ways; the first is that if an organ is constantly insulted and the damage is overwhelming the capacity of stem cells for functional repair, a non-functional repair will take place, such as the formation of scar tissue, which will interfere with normal function leading to chronic disease. The second, in aging population, the self-repair capacity is reduced leading to cumulative organ damage from the same insult that may not cause disease in youth. These two problems are all related to the shortage of stem cells.
Now you may wonder how to make more stem cells available for regenerative medicine? Let’s first examine where stem cells are in our body. We all start from a single fertilized egg cell in our mom’s womb. During the embryonic period, the embryo develops into three layers, the ectoderm, the endoderm, and the mesoderm; and stem cells rapidly divide and differentiate to different organs. Some stem cells are also stored in our organs, such as mesenchymal stem cells in the mesoderm organs and bone marrow stem cells in our bone marrow. These stem cells are mobilized locally and from bone marrow when an organ is injured and needs to be repaired. The stem cell can be removed from our body, expanded outside of our body, and then reintroduced to our body to repair the injured organ.
Now you may ask how do stem cells work in our body? First, stem cells once in our body need to know where to go. On the surface of the stem cells there are detectors that can detect the injury signal, then where the injury signal comes from? Second, once the stem cells arrive in the injured organ, how do they act to repair the injury?
The first, how does an injured organ send signals? When an organ is injured, it will release some cellular molecules or chemicals, attracting stem cells to the injured site for repairing. But if there are not enough stem cells, a scar tissue will be formed to make a non-functional repair. The tissue will no longer send injury signals. If you introduce stem cells into the body, they don’t know where to go. If you simply force stem cells into the injured organ such as through injection, they would not stay in place. Let’s think about the ceramic tiles covered on the floor in your house, what would happen if one of the tiles was damaged, but cannot be replaced because you do not have the replacement tile? You may use cement to cover the empty space, which doesn’t look or feel the same. Now, you get the replacement tile, what you would do is to remove the cement first, and then place the tile in place.
The non-functionally repaired organ was covered by scar tissue, to repair it we need to remove the scar tissue first. This scar tissue removing re-activates the tissue injury signaling, or changes the injury from chronic to acute state, calling for self-repair mechanism to work again. By providing sufficient stem cells through cell expansion from the same patient, the re-repair takes place, leading to organ regeneration.
The second, how do stem cells repair the injured organ? We did an experiment. We removed mesenchymal stem cells from monkey’s own fat tissue. After cell expansion, we packed the cells in a spheroid envelop composed of biodegradable materials; we call it Biosynsphere. We used the biosynspheres as bio-ink and applied the bio-ink to a novel 3D bio-printer to produce a stem cell vascular graft that was covered by a prosthetic vascular graft. The hybrid vascular graft was implanted as an interposition graft to replace a 2-cm-long segment of the abdominal aorta in the monkeys. We observed the changes of the implanted grafts at different times, and found that a complete vessel structure was formed about 4 weeks after the implantation, including endothelium layer, smooth muscle layer, and integrated collagen structure. In this process, anticoagulant heparin was used only in the first 5 days to prevent blood clotting. We made 47 implantations in 34 monkeys, and all of the regenerated vessels have normal function for the longest observation of more than 280 days.
I need to tell you that the mesenchymal stem cells are removed from the monkey’s own body, only 5 gram fat tissue is sufficient for a 2 cm vascular graft. It has no problem at all to remove 5 gram fat from anyone of us, even you are a skim model girl. If you say “I am too old”; no problem, you can ask your son or grandson to donate 5 gram fat for your use. It has been proven it does work well in monkeys.
So what can we conclude? First, injured organ is capable of a self-regeneration as long as there are sufficient repair materials supplied; second, the fat tissue mesenchymal stem cells are good enough and efficient for regeneration of multiple tissues of the blood vessel; and, third, personalized medicine is realized by rejuvenation of the naturally occurred self-repair process. This process isorchestrated by the injured site. We call this “Destination-Engaged Vector Evolving Lineage Organ Regeneration”, or simply called DEVELOR.
Thus, we can use our own stem cells to repair cumulative damages at early stage, preventing the development of the end stage of chronic disease. This will transform our medical practice from disease-based medication to personalized healthcare focusing on improving the quality of life, not simply expanding life span. By 2050, most of you will reach to age 60, I hope when you gather together then, you will talk about something more exciting than saving money for disease.
Thanks all.
馮莉 譯四川大學華西醫院再生醫學研究中心（成都 610041）Email: fenglily31@hotmail.com
假如我們偶遇年逾古稀長輩們的閑聊，我們大概會聽到這些內容：“最近我的心臟剛裝了支架”“醫生告訴我需要裝 7 個支架，我現在只裝了 2 個”等等。然后，討論的話題必然會過渡到如何存錢治病。“存錢治病”本身似乎也已經成為現代老年群體必須面對的一種疾病，我給這種病起了個名字，叫做“人口老齡化綜合征”。那么，到底有多少人已經或者即將步入老齡呢？據世界衛生組織數據顯示，從 2000 年到 2050 年，全球 60 歲以上人口將從 6 億 500 萬飆升至 20 億，更可怕的是，其在全球總人口中的比例將從 11% 上升到 22%。
人均期望壽命的不斷延長絕對是件好事。可我們也應當看到，近 80% 的老齡人口不得不承受各種嚴重疾病帶來的痛苦和困擾。試想，如果我們整天躺在病床上，依靠各種藥物度過從 80 歲到 90 歲的每個日夜，還必須時刻擔心高額的醫療費用。這樣的“高壽”，又有什么意義呢？
接下來你一定會問我這樣的問題：既然 3D 生物打印血管已經成為現實，那么是否可以使用該技術打印人體器官，通過移植取代受損臟器，從而延長我們的生命呢？當然，3D 生物打印技術絕對可以讓這種夢想成為現實。但我要告訴大家，我和我的團隊不會將人體器官打印作為我們的目標。因為，器官移植只是針對疾病終末期的一種傳統治療方式，這種方式確實能夠挽救生命，但它仍然不能滿足當代人們對提高生命質量的需求。我堅信，聚焦于人類生命質量的提高，將傳統的“以病為本”的醫療模式向“以人為本”的個性化健康干預模式轉變，才是醫學發展的正確方向。
最近我的一個朋友被診斷為動脈粥樣硬化，他的冠狀動脈已經堵塞 30%。但醫生對此束手無策。我的朋友只能被動地服用一些降膽固醇的藥物來減緩而不是阻止斑塊的長大。動脈硬化是不可逆的，他只能坐等斑塊長大，甚至等到可能危及其生命時，才能通過搭橋手術或放置血管支架以重新打通血管。換句話說，在血管堵塞程度達到現有手術治療的標準之前，我朋友什么都干不了。這，就是標準的“以病為本”的傳統醫療模式。可是，當疾病達到治療“標準”的時候，我朋友身體內的許多器官已經因為長期血供不足而受到損害，他已經由于這種非常“個性化”的因素，患上了諸多慢性疾病。
朋友很無奈地問我，醫生為何不能立即阻止斑塊生長或者直接去除斑塊呢？那樣的話，他的病根本就不會發展到終末期。我告訴他，雖然當前的醫療水平還無法達到他的要求，但只要付諸行動，在未來我們一定能夠做到。現代醫學知識的積累和來源于臨床實踐的大數據信息，為創造“以人為本”的新技術提供了支撐，這種新醫療技術，就是我們所說的“再生醫學”。
再生醫學是什么？我們為什么需要再生醫學？它如何為攻克疾病服務？簡言之，再生醫學就是利用干細胞及其相關技術，使受損組織器官恢復功能的一種綜合方法。干細胞廣泛存在于我們體內，其具有修復受傷組織的能力。舉例而言，假如你的手不幸被劃破，即使你不接受任何治療，傷口也會自動愈合，這就是自我修復。在修復過程中，受傷組織會先釋放出損傷信號，促使體內的修復材料運送到損傷部位。這種修復材料就是干細胞。也就是說，干細胞就是一種自然存在的“個性化”治療藥物。
既然我們已經具備自我修復材料—干細胞，為何還會患上慢性疾病呢？這主要基于兩個方面的原因：一、當組織器官長期持續受損，其損傷超過干細胞的自我修復能力時，機體就會進入一種叫非功能性修復的狀態，例如瘢痕組織形成，它會阻礙組織器官發揮正常功能，導致慢性疾病發生；二、相同的損傷，在年輕的時候能夠自我修復，而到了老年，由于自我修復能力降低、修復不完全，因此損傷不斷累積，最終產生慢性疾病。這兩種原因其實歸根結底就是干細胞不足。
接下來你肯定會問，那要怎樣才能獲取足夠多的干細胞以用于再生醫學？首先我們需要確定干細胞在體內所處的位置。我們的人生旅程都開始于母親子宮里的一個受精卵細胞。在胚胎階段，胚胎發育為 3 個胚層：外胚層、內胚層和中胚層。期間，干細胞快速分裂并分化形成不同的器官。其中一部分干細胞會在出生后一直儲存在我們的器官里，如中胚層器官中的間充質干細胞、骨髓中包含的骨髓干細胞。與之相應，當器官受損需要修復時，干細胞有兩種來源：一是器官自身含有的干細胞，它們立刻可以原位修復；二是骨髓來源干細胞，從骨髓遷移至受損器官進行修復。這是人體內的自然修復方式，而醫學上運用干細胞進行人為治療的常用方式是將干細胞從體內取出，在體外培養擴增甚至修飾，然后被重新輸入體內去修復受損器官。
干細胞在體內如何工作呢？干細胞一旦返回體內，首先需要明確去哪兒？干細胞的表面具有各種偵測“損傷信號”的“探測器”，可“損傷信號”是從哪里來的呢？另外，一旦干細胞抵達受損器官，他們又是怎樣修復損傷的呢？
第一個問題，受損器官怎樣釋放損傷信號？當某個器官受損時，它會釋放一些細胞因子或化學物質，從而吸引干細胞去進行修復。但如果干細胞數量不足，非功能性修復就會發生，并形成瘢痕組織。一旦瘢痕組織形成，受損器官則不會再釋放信號。如果這時將體外培養的干細胞送回體內，由于沒有信號，它們并不知道受損器官在哪里，也就無法起到修復的作用。即使采用簡單粗暴的方式，比如將干細胞直接注射到受損器官，他們也不會乖乖地留在損傷處。大家可以想象一下家中的地磚，如果某塊地磚不小心碎掉，而此刻家里又沒有可替換的瓷磚，大家會怎么干？你有可能先用水泥來填補，但這就跟原來的地磚不一樣了。你不甘心，于是去市場買到同款瓷磚，但你需要先把那堆水泥去掉，才能把瓷磚貼上去。
同樣的道理，非功能性修復后的器官被瘢痕組織包覆，必須先將瘢痕組織去除，才能重新修復損傷。瘢痕組織去除后會重新釋放損傷信號，或者說將慢性損傷變為急性損傷，從而重新啟動自我修復機制。這時通過體外擴增足夠量的患者自體干細胞引入患者體內修復受損器官，器官再生將得以實現。
第二個問題，干細胞如何修復受損器官？在一項實驗中，我們從恒河猴自體脂肪組織中提取了間充質干細胞。在細胞擴增之后，將這些干細胞封裝在一層生物可降解材料制作的球狀包裹中，我們稱之為“生物磚”。這些“生物磚”作為墨汁被 3D 打印機打印成類似血管的管腔狀結構，其外層用人工血管包覆。然后，我們通過外科手術將 2 cm 打印的人工血管替換恒河猴的一段腹主動脈。通過不同時間點觀察植入血管的變化，我們發現在手術 4 周后，人工血管內就產生了完整的血管結構，包括內皮層、平滑肌層及膠原支持結構。在整個過程中，只需在前 5 天對恒河猴使用抗凝劑-肝素以防止凝血。截至目前，在 34 只恒河猴，47 次手術，最長達 280 多天的觀察過程中，所有移植的人工血管都在其體內發揮著正常功能。
我想告訴大家，實驗所用的間充質干細胞均從恒河猴自身提取。僅 5 g 脂肪組織就足夠制作出 2 cm 人工血管。提取 5 g 脂肪對任何一個人來說都不是問題，哪怕你是一名骨感超模。如果你認為自己年紀太大，不適合提取干細胞。請放心，可以請你的兒女或者孫輩捐獻 5 g 脂肪。猴子實驗已經證明這同樣具備可操作性。
綜上所述，第一，只要提供充足的再生材料，受損組織就能夠進行自我再生。其次，脂肪間充質干細胞完全可以滿足血管中多種組織的再生需要。第三，個性化醫療通過再次激活個體自主修復系統實現，這個過程由受損部位調控。我把這套理論體系稱為“Destination-Engaged Vector Evolving Lineage Organ Regeneration”，簡稱為 DEVELOR。
因此，我們能夠利用自身干細胞在疾病早期對累積損傷進行修復，防止病癥發展為慢性疾病終末期。這將有助于“以病為本”的傳統醫療模式向聚焦于提高生命質量，而不僅是延長壽命的“以人為本”的健康模式轉變。到 2050 年，當在座的大多數都已年逾古稀時，我希望大家再次相聚時，會聊一些比存錢治病更有趣的事情。
謝謝大家。