Cryopreservation of complex systems: The missing link in the regenerative medicine supply chain
Cryopreservation of complex systems: The missing link in the regenerative medicine supply chain
复制标题
DOI：
10.1089/rej.2006.9.279
复制
发表时间：
2006-06-01
影响因子：
2.6
通讯作者：
Wu, Jun
中科院分区：
文献类型：
--
作者：
Fahy, Gregory M.;Wowk, Brian;Wu, Jun
移植可以被视为一种形式的“抗衰老药物”，被广泛认为是有效地延长人类寿命。目前美国每年器官移植数量为2万例，但每年的需求可能接近90万例。尸体和活体相关的供体来源不太可能提供所需的所有移植，但供需之间的差距原则上可以通过再生医学领域来消除，包括目前的组织工程领域，通过该领域，细胞，组织，甚至器官替代品正在实验室中产生。如果是这样的话，它可以使美国超过30%的死亡大大推迟，使活到80岁的概率提高两倍，活到90岁的几率提高10倍以上。然而，这一承诺取决于将再生医学产品实际分发给有需要的患者的能力，以及以允许适当库存控制和质量保证的方式生产这些产品的能力。为此，低温保存（冷冻保存）细胞、组织甚至整个实验室生产的器官的能力可能是必不可少的。直到最近，对大多数观察家来说，器官的冷冻保存似乎是一个遥远的前景，但过去几年的发展正在迅速改变将最困难和脆弱的器官无限期保存的科学基础。动物的肠道和卵巢已经被冷冻、解冻，并在移植后显示出功能，但重要器官的保存很可能需要玻璃化。通过玻璃化冷冻，防止了所有冰的形成，并且器官在低于玻璃化转变温度（T-G）的玻璃态下被保存。玻璃化冷冻已成功用于许多组织，如静脉、动脉、软骨和心脏瓣膜，甚至成功用于整个卵巢。对于重要器官，玻璃化冷冻的一个重要的近期里程碑是在冷却至约45 ℃的平均肾内温度后常规恢复兔肾的能力，如移植后生命支持功能所证实的。这个温度对于长期储存来说还不够低，但是在-45摄氏度以下保存的研究仍在继续，并且已经获得了一些令人鼓舞的初步证据，表明肾脏可以在玻璃化冷冻后维持生命。组织工程和干细胞器官生成的全面发展，再加上储存这些实验室生产的产品的能力，理论上即使在根本上没有改善减缓衰老过程的情况下，也可以大大提高平均预期寿命。
Transplantation can be regarded as one form of "antiaging medicine" that is widely accepted as being effective in extending human life. The current number of organ transplants in the United States is on the order of 20,000 per year, but the need may be closer to 900,000 per year. Cadaveric and living-related donor sources are unlikely to be able to provide all of the transplants required, but the gap between supply and demand can be eliminated in principle by the field of regenerative medicine, including the present field of tissue engineering through which cell, tissue, and even organ replacements are being created in the laboratory. If so, it could allow over 30% of all deaths in the United States to be substantially postponed, raising the probability of living to the age of 80 by a factor of two and the odds of living to 90 by more than a factor of 10. This promise, however, depends on the ability to physically distribute the products of regenerative medicine to patients in need and to produce these products in a way that allows for adequate inventory control and quality assurance. For this purpose, the ability to cryogenically preserve (cryopreserve) cells, tissues, and even whole laboratory-produced organs may be indispensable. Until recently, the cryopreservation of organs has seemed a remote prospect to most observers, but developments over the past few years are rapidly changing the scientific basis for preserving even the most difficult and delicate organs for unlimited periods of time. Animal intestines and ovaries have been frozen, thawed, and shown to function after transplantation, but the preservation of vital organs will most likely require vitrification. With vitrification, all ice formation is prevented and the organ is preserved in the glassy state below the glass transition temperature (T-G). Vitrification has been successful for many tissues such as veins, arteries, cartilage, and heart valves, and success has even been claimed for whole ovaries. For vital organs, a significant recent milestone for vitrification has been the ability to routinely recover rabbit kidneys after cooling to a mean intrarenal temperature of about 45 degrees C, as verified by life support function after transplantation. This temperature is not low enough for long-term banking, but research continues on preservation below -45 degrees C, and some encouraging preliminary evidence has been obtained indicating that kidneys can support life after vitrification. Full development of tissue engineering and organ generation from stem cells, when combined with the ability to bank these laboratory-produced products, in theory could dramatically increase median life expectancy even in the absence of any improvements in mitigating aging processes on a fundamental level.